manual clsi 2005

M100-S15Vol. 25 No. 1

Replaces M100-S14January 2005 Vol. 24 No. 1

Performance Standards for AntimicrobialSusceptibility Testing; Fifteenth Informational Supplement

This document provides updated tables for the Clinical and Laboratory StandardsInstitute (CLSI)/NCCLS antimicrobial susceptibility testing standards M2-A8 andM7-A6.An informational supplement for global application developed through the Clinical andLaboratory Standards Institute consensus process.

The Clinical and Laboratory Standards Institute (CLSI)(formerly NCCLS) is an international, interdisciplinary,nonprofit, standards-developing, and educationalorganization that promotes the development and use ofvoluntary consensus standards and guidelines within thehealthcare community. It is recognized worldwide for theapplication of its unique consensus process in thedevelopment of standards and guidelines for patienttesting and related healthcare issues. Our process is basedon the principle that consensus is an effective and cost-effective way to improve patient testing and healthcareservices.

In addition to developing and promoting the use ofvoluntary consensus standards and guidelines, we providean open and unbiased forum to address critical issuesaffecting the quality of patient testing and health care.

PUBLICATIONS

A document is published as a standard, guideline, orcommittee report.

Standard A document developed through the consensusprocess that clearly identifies specific, essentialrequirements for materials, methods, or practices for usein an unmodified form. A standard may, in addition,contain discretionary elements, which are clearlyidentified.

Guideline A document developed through the consensusprocess describing criteria for a general operatingpractice, procedure, or material for voluntary use. Aguideline may be used as written or modified by the userto fit specific needs.

Report A document that has not been subjected toconsensus review and is released by the Board ofDirectors.

CONSENSUS PROCESS

The CLSI voluntary consensus process is a protocolestablishing formal criteria for:

• the authorization of a project

• the development and open review of documents

• the revision of documents in response to commentsby users

• the acceptance of a document as a consensusstandard or guideline.

Most documents are subject to two levels ofconsensus–“proposed” and “approved.” Depending onthe need for field evaluation or data collection,documents may also be made available for review at anintermediate consensus level.

Proposed A consensus document undergoes the firststage of review by the healthcare community as aproposed standard or guideline. The document shouldreceive a wide and thorough technical review, includingan overall review of its scope, approach, and utility, and aline-by-line review of its technical and editorial content.

Approved An approved standard or guideline hasachieved consensus within the healthcare community. Itshould be reviewed to assess the utility of the finaldocument, to ensure attainment of consensus (i.e., thatcomments on earlier versions have been satisfactorilyaddressed), and to identify the need for additionalconsensus documents.

Our standards and guidelines represent a consensusopinion on good practices and reflect the substantialagreement by materially affected, competent, andinterested parties obtained by following CLSI’sestablished consensus procedures. Provisions in CLSIstandards and guidelines may be more or less stringentthan applicable regulations. Consequently, conformanceto this voluntary consensus document does not relieve theuser of responsibility for compliance with applicableregulations.

COMMENTS

The comments of users are essential to the consensusprocess. Anyone may submit a comment, and allcomments are addressed, according to the consensusprocess, by the committee that wrote the document. Allcomments, including those that result in a change to thedocument when published at the next consensus level andthose that do not result in a change, are responded to bythe committee in an appendix to the document. Readersare strongly encouraged to comment in any form and atany time on any document. Address comments to Clinicaland Laboratory Standards Institute, 940 West ValleyRoad, Suite 1400, Wayne, PA 19087, USA.

VOLUNTEER PARTICIPATION

Healthcare professionals in all specialties are urged tovolunteer for participation in CLSI projects. Pleasecontact us at [email protected] or +610.688.0100 foradditional information on committee participation.

Clinical and Laboratory Standards InstituteProviding NCCLS standards and guidelines, ISO/TC 212 standards, and ISO/TC 76 standards

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Performance Standards for Antimicrobial Susceptibility Testing;Fifteenth Informational Supplement

Abstract

The supplemental information presented in this document is intended for use with the antimicrobialsusceptibility testing procedures published in the following Clinical and Laboratory Standards Institute(CLSI)/NCCLS approved standards: M2-A8—Performance Standards for Antimicrobial DiskSusceptibility Tests; Approved Standard—Eighth Edition; and M7-A6—Methods for DilutionAntimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Sixth Edition.The standards contain information about both disk (M2) and dilution (M7) test procedures for aerobicbacteria.

Clinicians depend heavily on information from the clinical microbiology laboratory for treatment of theirseriously ill patients. The clinical importance of antimicrobial susceptibility test results requires that thesetests be done under optimal conditions and that laboratories have the capability to provide results for thenewest antimicrobial agents.

The tabular information presented here represents the most current information for drug selection,interpretation, and quality control using the procedures standardized in M2 and M7. Users should replacethe tables published earlier with these new tables. (Changes in the tables since the most recent editionappear in boldface type.)

Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial SusceptibilityTesting; Fifteenth Informational Supplement. CLSI document M100-S15 (ISBN 1-56238-556-9). Clinicaland Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898USA, 2005.

The data in the interpretive tables in this supplement are valid only if themethodologies in M2-A8—Performance Standards for Antimicrobial DiskSusceptibility Tests; Approved Standard—Eighth Edition; and M7-A6—Methods forDilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Sixth Edition are followed.

Vol. 25 No. 1 M100-S15

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January 2005 M100-S15

Volume 25 Number 1

Matthew A. Wikler, M.D., M.B.A., FIDSAFranklin R. Cockerill, III, M.D.William A. Craig, M.D.Michael N. Dudley, Pharm.D.George M. Eliopoulos, M.D.David W. Hecht, M.D.Janet F. Hindler, MCLS, M.T.(ASCP)Donald E. Low, M.D.Daniel J. Sheehan, Ph.D.Fred C. Tenover, Ph.D., ABMMJohn D. Turnidge, M.D.Melvin P. Weinstein, M.D.Barbara L. Zimmer, Ph.D.

Mary Jane Ferraro, Ph.D., M.P.H.Jana M. Swenson, M.M.Sc.

M100-S15ISBN 1-56238-556-9ISSN 0273-3099

Performance Standards for Antimicrobial Susceptibility Testing;Fifteenth Informational Supplement


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This publication is protected by copyright. No part of it may be reproduced, stored in a retrieval system,transmitted, or made available in any form or by any means (electronic, mechanical, photocopying,recording, or otherwise) without prior written permission from Clinical and Laboratory Standards Institute,except as stated below.

Clinical and Laboratory Standards Institute hereby grants permission to reproduce limited portions of thispublication for use in laboratory procedure manuals at a single site, for interlibrary loan, or for use ineducational programs provided that multiple copies of such reproduction shall include the followingnotice, be distributed without charge, and, in no event, contain more than 20% of the document’s text.

Reproduced with permission, from CLSI/NCCLS publication M100-S15—PerformanceStandards for Antimicrobial Susceptibility Testing; Fifteenth Informational Supplement(ISBN 1-56238-556-9). Copies of the current edition may be obtained from Clinical andLaboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania19087-1898, USA.

Permission to reproduce or otherwise use the text of this document to an extent that exceeds theexemptions granted here or under the Copyright Law must be obtained from Clinical and LaboratoryStandards Institute by written request. To request such permission, address inquiries to the Executive VicePresident, Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne,Pennsylvania 19087-1898, USA.

Copyright ©2005. Clinical and Laboratory Standards Institute.

Suggested Citation

(Clinical and Laboratory Standards Institute/NCCLS. Performance Standards for AntimicrobialSusceptibility Testing; Fifteenth Informational Supplement. CLSI/NCCLS document M100-S15 [ISBN 1-56238-556-9]. Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne,Pennsylvania 19087-1898 USA, 2005.)

Fifteenth Informational Supplement Eleventh Informational SupplementJanuary 2005 January 2001

Fourteenth Informational Supplement Tenth Informational SupplementJanuary 2004 January 2000

Thirteenth Informational Supplement Ninth Informational SupplementJanuary 2003 January 1999

Twelfth Informational Supplement Eighth Informational SupplementJanuary 2002 January 1998

ISBN 1-56238-556-9ISSN 0273-3099

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Committee Membership

Area Committee on Microbiology

Mary Jane Ferraro, Ph.D., M.P.H.ChairholderMassachusetts General HospitalBoston, Massachusetts

James H. Jorgensen, Ph.D.Vice-ChairholderUniversity of Texas Health ScienceCenterSan Antonio, Texas

Donald R. Callihan, Ph.D.BD Diagnostic SystemsSparks, Maryland

David L. Sewell, Ph.D.Veterans Affairs Medical CenterPortland, Oregon

Thomas R. Shryock, Ph.D.Lilly Research LaboratoriesGreenfield, Indiana

Jana M. Swenson, M.M.Sc.Centers for Disease Control andPreventionAtlanta, Georgia

Michael L. Wilson, M.D.Denver Health Medical CenterDenver, Colorado

Advisors

Ellen Jo Baron, Ph.D.Stanford Univ. Hospital & MedicalSchoolStanford, California

Lynne S. Garcia, M.S.LSG & AssociatesSanta Monica, California

Richard L. Hodinka, Ph.D.Children’s Hospital of PhiladelphiaPhiladelphia, Pennsylvania

Michael A. Pfaller, M.D.University of Iowa College of MedicineIowa City, Iowa

Robert P. Rennie, Ph.D.University of Alberta HospitalEdmonton, Alberta, Canada

Melvin P. Weinstein, M.D.Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey

Gail L. Woods, M.D.ARUP Research InstituteSalt Lake City, Utah

Subcommittee on Antimicrobial Susceptibility Testing

Matthew A. Wikler, M.D., M.B.A.,FIDSAChairholderPeninsula Pharmaceuticals, Inc.Alameda, California

Franklin R. Cockerill, III, M.D.Mayo Clinic/Mayo FoundationRochester, Minnesota

William A. Craig, M.D.University of WisconsinMadison, Wisconsin

Michael N. Dudley, Pharm.D.Diversa CorporationSan Diego, California

George M. Eliopoulos, M.D.Beth Israel Deaconess Medical CenterBoston, Massachusetts

David W. Hecht, M.D.Loyola University Medical CenterMaywood, Illinois

Janet F. Hindler, MCLS, M.T.(ASCP)UCLA Medical CenterLos Angeles, California

Donald E. Low, M.D.Mount Sinai HospitalToronto, Ontario, Canada

Daniel J. Sheehan, Ph.D.Pfizer Inc.New York, New York

Fred C. Tenover, Ph.D., ABMMCenters for Disease Control andPreventionAtlanta, Georgia

John D. Turnidge, M.D.Women’s and Children’s HospitalNorth Adelaide, Australia

Melvin P. Weinstein, M.D.Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey

Barbara L. Zimmer, Ph.D.Dade Behring MicroScanWest Sacramento, California

Advisors

Patricia A. Bradford, Ph.D.Wyeth ResearchPearl River, New York

John S. Bradley, M.D.Children’s Hospital and Health CenterSan Diego, California

Steven D. Brown, Ph.D.The Clinical Microbiology InstituteWilsonville, Oregon

Karen Bush, Ph.D.Johnson & Johnson PharmaceuticalResearch InstituteRaritan, New Jersey

Robert K. Flamm, Ph.D.Focus Technologies, Inc.Herndon, Virginia

Lawrence V. Friedrich, Pharm.D.Cubist PharmaceuticalsMt. Pleasant, South Carolina

Dwight J. Hardy, Ph.D.University of Rochester MedicalCenterRochester, New York

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Advisors (Continued)

Yoichi Hirakata, M.D., Ph.D.Nagasaki University School ofMedicine and DentistryNagasaki, Japan

Ronald N. Jones, M.D.The JONES Group/JMINorth Liberty, Iowa

Gunnar Kahlmeter, M.D., Ph.D.ESCMIDSweden

John E. McGowan, Jr., M.D.Emory University, Rollins School ofPublic HealthAtlanta, Georgia

Linda A. Miller, Ph.D.GlaxoSmithKlineCollegeville, Pennsylvania

Susan D. Munro, M.T.(ASCP)Stanford University Hospital andClinicsStanford, California

Charles H. Nightingale, Ph.D.Hartford HospitalHartford, Connecticut

John H. Powers, III, M.D., FACPFDA Center for Drug Evaluation andResearchRockville, Maryland

L. Barth Reller, M.D.Duke University Medical CenterDurham, North Carolina

Robert P. Rennie, Ph.D.University of Alberta HospitalEdmonton, Alberta, Canada

Sally Selepak, M.T.(ASCP)FDA Center for Devices andRadiological HealthRockville, Maryland

Jana M. Swenson, M.M.Sc.Centers for Disease Control andPreventionAtlanta, Georgia

George H. Talbot, M.D.Talbot Advisors LLCWayne, Pennsylvania

Staff

Clinical and Laboratory StandardsInstitute Wayne, Pennsylvania

Tracy A. Dooley, M.L.T.(ASCP)Staff Liaison

Donna M. WilhelmEditor

Melissa A. LewisAssistant Editor

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Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Committee Membership. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Updated Information in This Edition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Subcommittee on Antimicrobial Susceptibility Testing Mission Statement . . . . . . . . . . . . . . . . . . . . 17

M2-A8 Performance Standards for Antimicrobial Disk Susceptibility Tests;Approved Standard—Eighth Edition

Introduction to Tables 1 through 1A and 2A through 2I for Use With M2-A8—Disk Diffusion. . . . 19

Table 1. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should BeConsidered for Routine Testing and Reporting on Nonfastidious Organisms by Clinical MicrobiologyLaboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

Table 1A. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should BeConsidered for Routine Testing and Reporting on Fastidious Organisms by Clinical MicrobiologyLaboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

Tables 2A-2I. Zone Diameter Interpretive Standards and Equivalent Minimal InhibitoryConcentration (MIC) Breakpoints for:

2A. Enterobacteriaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

2B. Pseudomonas aeruginosa, Acinetobacter spp., Stenotrophomonas maltophilia, and Burkholderiacepacia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

2C. Staphylococcus spp.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

2D. Enterococcus spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52

2E. Haemophilus spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

2F. Neisseria gonorrhoeae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60

2G. Streptococcus pneumoniae. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64

2H. Streptococcus spp. Other Than Streptococcus pneumoniae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66

2I. Vibrio cholerae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69

Table 3. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of Disk DiffusionTesting of Nonfastidious Organisms (Using Mueller-Hinton Medium Without Blood or OtherSupplements) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70


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Table 3A. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of Disk DiffusionTesting of Fastidious Organisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72

Table 3B. Reference Guide to Quality Control Testing Frequency. . . . . . . . . . . . . . . . . . . . . . . . . . . 74

Table 4. Suggestions for Verification of Antimicrobial Susceptibility Test Results and Confirmationof Organism Identification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76

Glossary I (Part 1). ß-lactams: Class and Subclass Designation and Generic Name . . . . . . . . . . . . . 78

Glossary I (Part 2). Non-ß-lactams: Class and Subclass Designation and Generic Name . . . . . . . . . 79

Glossary II. Abbreviations/Routes of Administration/Drug Class for Antimicrobial Agents Listed inM100-S15. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80

List of Identical Abbreviations Used for More Than One Antimicrobial Agent in U.S. DiagnosticProducts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83

Summary of Comments and Subcommittee Responses (M2-Disk Diffusion) . . . . . . . . . . . . . . . . . . 84

M7-A6 Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Sixth Edition

Introduction to Tables 1 Through 1B and 2A Through 2L for Use With M7-A6—MIC Testing. . . . 87

Table 1. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should BeConsidered for Routine Testing and Reporting on Nonfastidious Organisms by Clinical MicrobiologyLaboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92

Table 1A. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should BeConsidered for Routine Testing and Reporting on Fastidious Organisms by Clinical MicrobiologyLaboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98

Table 1B. Suggested Grouping of Antimicrobial Agents That Should Be Considered for Testing andReporting on Potential Agents of Bioterrorism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101

Tables 2A-2L. MIC Interpretive Standards (µg/mL) for:

2A. Enterobacteriaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102

2B. Pseudomonas aeruginosa and Other Non-Enterobacteriaceae . . . . . . . . . . . . . . . . . . . . . . . . . 108

2C. Staphylococcus spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110

2D. Enterococcus spp.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116

2E. Haemophilus spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120

2F. Neisseria gonorrhoeae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124

2G. Streptococcus pneumoniae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126

2H. Streptococcus spp. Other Than Streptococcus pneumoniae. . . . . . . . . . . . . . . . . . . . . . . . . . . . 130

2I. Vibrio cholerae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134

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Contents (Continued)2J. Helicobacter pylori . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135

2K. Bacillus anthracis, Yersinia pestis, Burkholderia mallei, Burkholderia pseudomallei, andFrancisella tularensis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136

2L. Neisseria meningitidis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138

Table 3. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of MinimalInhibitory Concentrations (MICs) (µg/mL) of Nonfastidious Organisms (Using Cation-AdjustedMueller-Hinton Medium Without Blood or Other Nutritional Supplements) . . . . . . . . . . . . . . . . . . 140

Table 3A. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of MinimalInhibitory Concentrations (MICs) (µg/mL) of Fastidious Organisms. . . . . . . . . . . . . . . . . . . . . . . . 142

Table 3B. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of MinimalInhibitory Concentrations (MICs) (µg/mL) Generated in Cation-Adjusted Mueller-Hinton Broth+ 2% Defined Growth Supplement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144

Table 3C. Reference Guide to Quality Control Testing Frequency. . . . . . . . . . . . . . . . . . . . . . . . . . 145

Table 4. Solvents and Diluents for Preparation of Stock Solutions of Antimicrobial Agents . . . . . 146

Table 5. Scheme for Preparing Dilutions of Antimicrobial Agents to Be Used in Agar DilutionSusceptibility Tests. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149

Table 6. Scheme for Preparing Dilutions of Antimicrobial Agents to Be Used in Broth DilutionSusceptibility Tests. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150

Table 7. Suggested Modifications of Standard Methods for Susceptibility Testing ofListeria spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151

Table 8. Suggestions for Verification of Antimicrobial Susceptibility Test Results andConfirmation of Organism Identification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152

Glossary I (Part 1). ß-lactams: Class and Subclass Designation and Generic Name . . . . . . . . . . . 154

Glossary I (Part 2). Non-ß-lactams: Class and Subclass Designation and Generic Name . . . . . . . . 155

Glossary II. Abbreviations/Routes of Administration/Drug Class for Antimicrobial Agents Listedin M100-S15. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156

List of Identical Abbreviations Used for More Than One Antimicrobial Agent in U.S. DiagnosticProducts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159

Summary of Comments and Subcommittee Responses (M7-MIC Testing) . . . . . . . . . . . . . . . . . . . 160

Related CLSI/NCCLS Publications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163


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The Clinical and Laboratory Standards Institute consensus process, which is the mechanism for movinga document through two or more levels of review by the healthcare community, is an ongoing process.Users should expect revised editions of any given document. Because rapid changes in technology mayaffect the procedures, methods, and protocols in a standard or guideline, users should replace outdatededitions with the current editions of CLSI/NCCLS documents. Current editions are listed in the CLSIcatalog, which is distributed to member organizations, and to nonmembers on request. If yourorganization is not a member and would like to become one, and to request a copy of the catalog, contactus at: Telephone: +610.688.0100; Fax: +610.688.0700; E-Mail: [email protected]; Website:www.clsi.org.

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Updated Information in This Edition

This document includes all of the tables from the Clinical and Laboratory Standards Institute DiskDiffusion (M2) susceptibility testing and Aerobic Dilution (M7) susceptibility testing documents. Thereare several important changes to the tables that have resulted from meetings of the Subcommittee onAntimicrobial Susceptibility Testing during 2004. Included below is a summary of the changes in thisdocument, which supersede the tables published in 2004 and in earlier years.

Summary of Major Changes in This Document

The list includes the “major” changes in this document. Other minor or editorial changes have been madeto the general formatting and to some of the table footnotes. Boldface type is used to highlight the changesin each table.

Additions/Changes/Deletions

The following are additions or changes unless otherwise noted as a “deletion.”

Clarification of temperature range for incubation in “Testing Conditions” box (M2 and M7; Tables 2A-2K)

Enterobacteriaceae:

ESBL Testing (M2 and M7; Table 2A)Recommendations for testing Proteus mirabilis for ESBL production with slight modification of several screening test breakpoints Escherichia coli ATCC® 25922 for QC of ESBL phenotypic confirmatory test (M7 only) Clarification of QC frequency for ESBL screening and confirmatory tests

Non-Enterobacteriaceae:

Separate lists of antimicrobial agents suggested for testing and reporting for Pseudomonas aeruginosa,Acinetobacter spp., Burkholderia cepacia, and Stenotrophomonas maltophilia (M2 and M7; Table 1).Footnotes j (M2 and M7) and k (M7) were modified accordingly.

Qualification of suggestion that cefotaxime, ceftriaxone, and ceftizoxime be considered for reporting onlyon Pseudomonas spp. (not P. aeruginosa) and other nonfastidious, glucose-nonfermenting, gram-negativebacilli (Test/Report Group C) (M7; Table 1)

Polymyxin B

MIC interpretive criteria which can be used to predict results for colistin also (M7; Table 2B)

Trimethoprim-sulfamethoxazoleDisk diffusion interpretive criteria for B. cepacia (M2; Table 2B)

Staphylococcus spp.:

Clindamycin induction test Suggestions for quality assessment and quality control (M2 and M7; Table 2C and “Minimal QCRecommendations” box)

Daptomycin Test/Report Group B (M2 and M7; Table 1)


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Updated Information in This Edition (Continued)

Daptomycin (Continued)

Disk diffusion and MIC interpretive criteria (M2 and M7; Table 2C)Special broth and agar media recommendations for testing daptomycin (M7; Table 2C and “TestingConditions” box)

Flucloxacillin - results can be deducted from testing oxacillin (M7; Table 2C)

Gatifloxacin - revised interpretive criteria (M2 and M7; Table 2C)

Levofloxacin - revised interpretive criteria (M2 and M7; Table 2C)

Moxifloxacin Test/Report Group C (M2 and M7; Table 1)Disk diffusion and MIC interpretive criteria (M2 and M7; Table 2C)

Ofloxacin - revised interpretive criteria (M2 and M7; Table 2C)

TelithromycinTest/Report Group B (M2 and M7; Table 1)Revised Test/Report Group (M2 and M7; Table 2C)

Vancomycin Suggestion for detecting S. aureus strains with reduced susceptibility to vancomycin with reference toBHI vancomycin agar screen test (M2 and M7; Table 2C)

Oxacillin related issues/comments (M2 and M7; Table 2C)Clarification of recommendations for reporting beta-lactam results on oxacillin-susceptiblestaphylococci (M2 and M7; Table 2C)Expanded discussion on use of mecA and PBP 2a testsExpanded discussion on use of cefoxitin disk testStaphylococcus lugdunensis - cefoxitin (disk diffusion) and oxacillin (disk diffusion and MIC) interpretivecriteria for S. aureus should be used for S. lugdunensis

Enterococcus spp.:

Daptomycin Test/Report Group B for vancomycin-susceptible Enterococcus faecalis only (M2 and M7; Table 1)Disk diffusion and MIC interpretive criteria (M2 and M7; Table 2D)Special broth and agar media recommendations for testing daptomycin (M7; Table 2D “TestingConditions” box)

Haemophilus spp.:

TelithromycinTest/Report Group C (M2 and M7; Table 1A)Revised Test/Report Group (M2 and M7; Table 2E)

Vol. 25 No. 1 M100-S15

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Streptococcus pneumoniae:

Fluoroquinolones

Deleted “or” designation and eliminated the ability to use results from testing one fluoroquinolone topredict results for another fluoroquinolone (M2 and M7; Group B, Table 1A and Table 2G)

TelithromycinTest/Report Group B (M2 and M7; Table 1A)Revised Test/Report Group (M2 and M7; Table 2G)

Streptococcus spp. Other Than Streptococcus pneumoniae

Clindamycin Recommendation for detecting inducible clindamycin resistance in beta-hemolytic streptococci (M2 andM7; Table 2H)

Clindamycin and Erythromycin Recommendation for testing Group B streptococci for intrapartum prophylaxis (M2 and M7; Table 2H)

Daptomycin Test/Report Group C (M2 and M7; Table 1A)Disk diffusion and MIC interpretive criteria for beta-hemolytic streptococci only (M2 and M7; Table 2H)Special broth and agar media recommendations for testing daptomycin (M7; Table 2H “TestingConditions” box)

Potential Agents of Bioterrorism:

MIC Table expanded to include recommendations and interpretive criteria for Francisella tularensis(M7; Table 2K)

Neisseria meningitidis:

MIC interpretive standards listed in new table (M7; Table 2L)

QC Range Changes/Additions (Table 3):

Chloramphenicol - Staphylococcus aureus ATCC® 29213 (M7)

Colistin - Escherichia coli ATCC® 25922 (M2 and M7)Pseudomonas aeruginosa ATCC® 27853 (M2 and M7)

Dalbavancin - Staphylococcus aureus ATCC® 29213 (M7)Enterococcus faecalis ATCC® 29212 (M7)

Daptomycin - Enterococcus faecalis ATCC® 29212 (M7)


14


Doripenem - Staphylococcus aureus ATCC® 25923 (M2)Staphylococcus aureus ATCC® 29213 (M7)Escherichia coli ATCC® 25922 (M2 and M7)Enterococcus faecalis ATCC® 29212 (M7)Pseudomonas aeruginosa ATCC® 27853 (M2 and M7)

Doxycycline - Staphylococcus aureus ATCC® 29213 (M7)Enterococcus faecalis ATCC® 29212 (M7)

Polymyxin B - Escherichia coli ATCC® 25922 (M2 and M7)Pseudomonas aeruginosa ATCC® 27853 (M2 and M7)

Telavancin - Staphylococcus aureus ATCC® 25923 (M2)Staphylococcus aureus ATCC® 29213 (M7)Enterococcus faecalis ATCC® 29212 (M7)

Tigecycline - Staphylococcus aureus ATCC® 25923 (M2)Staphylococcus aureus ATCC® 29213 (M7) Escherichia coli ATCC® 25922 (M2 and M7)Pseudomonas aeruginosa ATCC® 27853 (M2)Enterococcus faecalis ATCC® 29212 added (M7)

Tigecycline - instructions for using fresh CAMHB for broth microdilution tests

QC Range Changes/Additions (Table 3A):

Dalbavancin - Streptococcus pneumoniae ATCC® 49619 (M7)

Doripenem - Streptococcus pneumoniae ATCC® 49619 (M2 and M7)Haemophilus influenzae ATCC® 49247 (M2 and M7)

Doxycycline - Streptococcus pneumoniae ATCC® 49619 (M7)

Telavancin - Streptococcus pneumoniae ATCC® 49619 (M2 and M7)

Tigecycline - Haemophilus influenzae ATCC® 49247 (M2 and M7)Neisseria gonorrhoeae ATCC® 49226 (M2) Streptococcus pneumoniae ATCC® 49619 (M2 and M7)

QC Ranges for MICs Generated in Cation-Adjusted MHB with Growth Supplement (M7; newTable 3B)

Reference Guide to QC Testing Frequency (M2, Table 3B; M7, Table 3C)

Clarification that recommendations in this table do not eliminate the need for routine weekly or daily QCtesting (M2, Table 3B; M7, Table 3C)

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It is important for users of M2-A8 and M7-A6 to recognize that commercial susceptibility testingdevices are not addressed in these standards. The methods described herein are generic referenceprocedures that can be used for routine susceptibility testing by clinical laboratories, or that canbe used by clinical laboratories to evaluate commercial devices for possible routine use. Resultsgenerated by the CLSI/NCCLS reference methods are used by the United States Food and DrugAdministration to evaluate the performance of commercial systems before clearance is given formarketing in the United States. Clearance by the FDA indicates that the agency concludes thatcommercial devices provide susceptibility results that are substantially equivalent to resultsgenerated using the CLSI/NCCLS reference methods for the organisms and antimicrobial agentsdescribed in the manufacturer’s approved package insert. Some laboratories could find that acommercial dilution, antibiotic gradient, colorimetric, turbidimetric, fluorometric, or othermethod is suitable for selective or routine use.


Indication that users of FDA-cleared antimicrobial susceptibility test systems should utilize QC limitslisted in the product literature (M7; Table 3C)

Suggestions for Verification of Antimicrobial Susceptibility Test Results and Confirmation ofOrganism Identification (MIC) (M2, Table 4; M7, Table 8)

Daptomycin-NS under Category I for the following organisms: Enterococcus spp.; Enterococcus faecalis;Enterococcus faecium; Staphylococcus aureus; Staphylococcus, coagulase-negative; Streptococcus, betagroup; and Streptococcus, viridans group (M2, Table 4; M7, Table 8)

Suggestion that laboratories report to their public health department Salmonella spp. found to beintermediate or resistant 3rd-generation cephalosporins and/or intermediate or resistant tofluoroquinolones or resistant to nalidixic acid. (M2, Table 4; M7, Table 8)

Suggested Modifications of Standard Methods for Susceptibility Testing:

Deletion:Recommendations for Neisseria meningitidis as standard recommendations of this species are now inTable 2L (M7, Table 7)

Solvents and Diluents for Preparation of Stock Solutions of Antimicrobial Agents

Colistin, Dalbavancin, Daptomycin, Doripenem, Polymyxin B, Telavancin, and Tigecycline (M2, Table 4)

Glossaries I and II

Colistin, Dalbavancin, Doripenem, Oritavancin, Polymyxin B, Telavancin, and Tigecycline added(Glossaries I and II)

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Vol. 25 No. 1 M100-S15

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Subcommittee on Antimicrobial Susceptibility Testing Mission Statement

The Subcommittee on Antimicrobial Susceptibility Testing is composed of representatives from theprofessions, government, and industry, including microbiology laboratories, government agencies,healthcare providers and educators, and pharmaceutical and diagnostic microbiology industries. Usingthe CLSI voluntary consensus process, the subcommittee develops standards that promote accurateantimicrobial susceptibility testing and appropriate reporting.

The mission of the Subcommittee on Antimicrobial Susceptibility Testing is to:

• Develop standard reference methods for antimicrobial susceptibility tests.

• Provide quality control parameters for standard test methods.

• Establish interpretive criteria for the results of standard antimicrobial susceptibility tests.

• Provide suggestions for testing and reporting strategies that are clinically relevant and cost-effective.

• Continually refine standards and optimize the detection of emerging resistance mechanisms through the development of new or revised methods, interpretive criteria, and quality control parameters.

• Educate users through multimedia communication of standards and guidelines.

• Foster a dialogue with users of these methods and those who apply them.

The ultimate purpose of the subcommittee’s mission is to provide useful information to enablelaboratories to assist the clinician in the selection of appropriate antimicrobial therapy for patient care.The standards and guidelines are meant to be comprehensive and to include all antimicrobial agents forwhich the data meet established CLSI/NCCLS guidelines. The values that guide this mission are quality,accuracy, fairness, timeliness, teamwork, consensus, and trust.


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For Use With M2-A8–Disk Diffusion M100-S15

©Clinical and Laboratory Standards Institute. All rights reserved. 19

Introduction to Tables 1 Through 1A and 2A Through 2I for Use With M2-A8—Disk Diffusion

I. Selecting Antimicrobial Agents for Testing and Reporting

A. Selection of the most appropriate antimicrobial agents to test and to report is a decision best madeby each clinical laboratory in consultation with the infectious disease practitioners and thepharmacy, as well as the pharmacy and therapeutics and infection control committees of themedical staff. The recommendations here for each organism group comprise agents of provenefficacy that show acceptable in vitro test performance. Considerations in the assignment of agentsto specific test/report groups include clinical efficacy, prevalence of resistance, minimizingemergence of resistance, cost, FDA indications, and current consensus recommendations for first-choice and alternative drugs, in addition to the specific issues described. Tests of selected agentsmay be useful for infection control purposes.

B. The listing of drugs together in a single box designates clusters of comparable agents that need notbe duplicated in testing, because interpretive results are usually similar and clinical efficacycomparable. In addition, an “or” designates a related group of agents that has an almost identicalspectrum of activity and interpretive results, and for which cross-resistance and susceptibility arenearly complete. Therefore, usually only one of the agents within each selection box (cluster orrelated group) need be selected for testing. Agents reported must be tested, unless reporting basedon testing another agent provides a more accurate result (e.g., susceptibility of staphylococci tocefazolin or cephalothin based on oxacillin testing), and they usually should match those includedin the hospital formulary; or else the report should include footnotes indicating the agents thatusually show comparable interpretive results. Unexpected results should be considered forreporting (e.g., resistance of Enterobacteriaceae to third-generation cephalosporins or imipenem).

On the following pages, you will find:

1. Tables 1 and 1A—Suggested groupings of U.S. FDA-approved antimicrobial agentsthat should be considered for routine testing and reporting by clinical microbiologylaboratories.

2. For each organism group, an additional table (Tables 2A through 2I) that contains:a. Recommended testing conditions.b. Minimal QC recommendations. (See also the M2-A8 text document, Section 10.)c. General comments for testing the organism group and specific comments for testing

particular drug/organism combinations.d. Suggested agents that should be considered for routine testing and reporting by

clinical microbiology laboratories as specified in Tables 1 and 1A (test/reportgroups A, B, C, U; the latter for “urine”).

e. Additional drugs that have an approved indication for the respective organismgroup, but would generally not warrant routine testing by a clinical microbiologylaboratory in the United States (test/report group O for “other”; test/report groupInv. for “investigational” [not yet FDA approved]).

f. Zone diameter interpretive criteria and equivalent MIC values which represent MICbreakpoints used in determining approximate zone diameter interpretive criteria.They relate to MICs determined by M7 methodology. Occasional discrepancies mayexist between M2 and M7 due to methodological limitations.

January 2005 Vol. 25 No. 1

©Clinical and Laboratory Standards Institute. All rights reserved.20

C. Test/Report Groups

1. As listed in Tables 1 and 1A, agents in Group A are considered appropriate for inclusionin a routine, primary testing panel, as well as for routine reporting of results for thespecific organism groups.

2. Group B comprises agents that are important clinically, particularly for nosocomialinfections, and they may warrant primary testing. However, they may be reported onlyselectively, such as when the organism is resistant to agents of the same class, as in GroupA. Other indications for reporting the result might include a selected specimen source(e.g., a third-generation cephalosporin for enteric bacilli from cerebrospinal fluid [CSF]or trimethoprim-sulfamethoxazole for urinary tract isolates); a polymicrobial infection;infections involving multiple sites; on request in case of allergy, intolerance, or failure torespond to an agent in Group A; or for reporting to infection control as an epidemiologicaid.

3. Group C comprises alternative or supplemental antimicrobial agents that may requiretesting in those institutions that harbor endemic or epidemic strains resistant to several ofthe primary drugs (especially in the same class, e.g., β-lactams or aminoglycosides); fortreatment of patients allergic to primary drugs; for treatment of unusual organisms (e.g.,chloramphenicol for extraintestinal isolates of Salmonella spp. or some vancomycin-resistant enterococci); or for reporting to infection control as an epidemiologic aid.

4. Group U (“urine”) lists certain antimicrobial agents (e.g., nitrofurantoin and certainquinolones) that are used only or primarily for treating urinary tract infections. Theseagents should not be routinely reported against pathogens recovered from other sites ofinfection. Other agents with broader indications may be included in Group U for specificurinary pathogens (e.g., P. aeruginosa).

5. Group O (“other”) includes agents that have a clinical indication for the organism groupbut are generally not candidates for routine testing and reporting in the United States.

6. Group Inv. (“investigational”) includes agents that are investigational for the organismgroup and have not yet been approved by the FDA.

D. Selective Reporting

Each laboratory should decide which agents in the tables to report routinely (Group A) and whichmight be reported only selectively (from Group B), in consultation with the infectious diseasepractitioners and the pharmacy, as well as the pharmacy and therapeutics and infection controlcommittees of the medical staff of the hospital. Selective reporting should help improve theclinical relevance of test reports and help minimize the selection of multiresistant nosocomialstrains by overuse of broad-spectrum agents. Results for Group B agents not reported routinelyshould be available on request, or they may be reported for selected specimens. Unexpectedresistance, when confirmed, should be reported (e.g., resistance to a secondary agent butsusceptibility to a primary agent).



II. Reporting Results

Recommended interpretive criteria are based on usual dosage regimens and routes ofadministration in the U.S.

A. Susceptible, intermediate, or resistant interpretations of zone diameter measurements are reportedand defined as follows:

1. Susceptible (S)

The “susceptible” category implies that an infection due to the strain may be appropriatelytreated with the dosage of antimicrobial agent recommended for that type of infection andinfecting species, unless otherwise contraindicated.

2. Intermediate (I)

The “intermediate” category includes isolates with antimicrobial agent MICs thatapproach usually attainable blood and tissue levels and for which response rates may belower than for susceptible isolates. The “intermediate” category implies clinicalapplicability in body sites where the drugs are physiologically concentrated (e.g.,quinolones and ß-lactams in urine) or when a high dosage of a drug can be used (e.g., ß-lactams). The “intermediate” category also includes a “buffer zone” which should preventsmall, uncontrolled technical factors from causing major discrepancies in interpretations,especially for drugs with narrow pharmacotoxicity margins.

3. Resistant (R)

Resistant strains are not inhibited by the usually achievable systemic concentrations of theagent with normal dosage schedules and/or fall in the range where specific microbialresistance mechanisms are likely (e.g., ß-lactamases) and clinical efficacy has not beenreliable in treatment studies.

B. For organisms excluded from Tables 2A through 2I (e.g., Campylobacter spp., Corynebacteriumspp., Bacillus spp.) studies are not yet adequate to develop reproducible, definitive standards tointerpret results. These organisms may require different media, different atmospheres ofincubation, or show marked strain-to-strain variation in growth rate. For these microorganisms,consultation with an infectious disease specialist is recommended for guidance in determining theneed for susceptibility testing and in the interpretation of results. Published reports in the medicalliterature and current consensus recommendations for therapy of uncommon microorganisms mayobviate the need for testing. If necessary, a dilution method usually will be the most appropriatetesting method, and this may require submitting the organism to a reference laboratory. Physiciansshould be informed of the limitations of results and advised to interpret results with caution.

If only “S” criteria are specified:For some organism/antimicrobial combinations, the absence of resistant strains precludesdefining any results categories other than “susceptible.” For strains yielding resultssuggestive of a “nonsusceptible” category, organism identification and antimicrobialsusceptibility test results should be confirmed. Subsequently, the isolates should be savedand submitted to a reference laboratory that will confirm results using a CLSI/NCCLSreference dilution method.



C. Policies regarding the generation of cumulative antibiograms should be developed in concert withthe infectious disease service, infection control personnel, and the pharmacy and therapeuticscommittee. Under most circumstances, the percentage of susceptible and intermediate resultsshould not be combined into the same statistics.

III. Therapy-Related Comments

Some of the comments in the tables relate to therapy concerns. These are denoted with an Rxsymbol. It may be appropriate to include some of these comments (or modification thereof) on thepatient report. An example would be inclusion of a comment on enterococcus susceptibilityreports from blood cultures that “enterococcal endocarditis requires combined therapy with high-dose penicillin or high-dose ampicillin or vancomycin or teicoplanin plus gentamicin orstreptomycin for bactericidal action.”

Antimicrobial dosage regimens often vary widely among practitioners and institutions. In somecases, the MIC interpretive criteria rely on pharmacokinetic-pharmacodynamic data using specifichuman dosage regimens. In cases where specific dosage regimens are important for properapplication of breakpoints, a therapy-related comment is included.

IV. Verification of Patient Results

Multiple test parameters are monitored by following the quality control recommendationsdescribed in this standard. However, acceptable results derived from testing quality control strainsdo not guarantee accurate results when testing patient isolates. It is important to review all of theresults obtained from all drugs tested on a patient’s isolate prior to reporting the results. Thisshould include but not be limited to ensuring that: 1) the antimicrobial susceptibility results areconsistent with the identification of the isolate; 2) the results from individual agents within aspecific drug class follow established hierarchy of activity rules (e.g., third-generation cephemsare more active than first- or second-generation cephems against Enterobacteriaceae); and 3) theisolate is susceptible to those agents for which resistance has not been documented (e.g.,vancomycin and Streptococcus spp.) and for which only “susceptible” interpretive criteria exist inM100.

Unusual or inconsistent results should be verified by checking for the following: 1) transcriptionerrors; 2) contamination of the test (recheck purity plates, etc.); and 3) previous results on thepatient (e.g., Did the patient have the same isolate with an unusual antibiogram previously?) If areason for the unusual or inconsistent result cannot be ascertained, a repeat of the susceptibilitytest or the identification or both of these is in order. Sometimes it is helpful to use an alternativetest method for the repeat test. A suggested list of results that may require verification is includedin Table 4. Each laboratory must develop its own policies for verification of unusual orinconsistent antimicrobial susceptibility test results. This list should emphasize those results thatare highly likely to impact patient care.



V. Warning

Some of the comments in the tables relate to dangerously misleading results that can occur whencertain antimicrobial agents are tested and reported as susceptible against specific organisms.These are denoted with the word “Warning.”

“Warning”: The following antimicrobial agent/organism combinations may appear active invitro but are not effective clinically and should not be reported as susceptible.

Location Organism Antimicrobial Agents That Must Notbe Reported as Susceptible

Table 2A Salmonella spp., Shigella spp. 1st- and 2nd-generation cephalosporins,and aminoglycosides

Table 2C oxacillin-resistant Staphylococcus spp. all penems, cephems, and other ß-lactams such as amoxicillin-clavulanicacid, piperacillin-tazobactam, andimipenem

Table 2D Enterococcus spp. aminoglycosides (except highconcentrations), cephalosporins,clindamycin, and trimethoprim-sulfamethoxazole

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Table 1. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should Be Consideredfor Routine Testing and Reporting on Nonfastidious Organisms by Clinical Microbiology Laboratories

Amikacin Amikacin Azithromycinb or clarithromycinb orerythromycinb

Daptomycins

Linezolid Quinupristin-

dalfopristinrAmoxicillin-clavulanic acid

or ampicillin-sulbactamPiperacillin-tazobactamTicarcillin-clavulanic acid

AztreonamCefoperazone Clindamycinb Vancomycinp

DaptomycinCefamandole or

cefonicid orcefuroxime

Linezolid

Telithromycinb

Cefepime Cefepime Trimethoprim-sulfamethoxazole

CefmetazoleCefoperazoneg

CefotetanCefoxitin

CiprofloxacinLevofloxacin

Vancomycin

Cefotaximeg, h, i orceftizoxime g, i orceftriaxoneg, h, i

ImipenemMeropenem

Ciprofloxacing orlevofloxacing

Tobramycin

ErtapenemImipenem or

meropenemMezlocillin or

piperacillinTicarcillinTrimethoprim-

sulfamethoxazoleg

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Aztreonam Ceftazidime (Both are helpfulindicators of extended-spectrum β-lactamases.) i

Netilmicin Chloramphenicolb Gentamicin(high-levelresistance screen only)

Ciprofloxacin orlevofloxacin orofloxacin

Gatifloxacin ormoxifloxacin

Streptomycin(high-level resistance screen only)Chloramphenicol b, g

Kanamycin Quinupristin-dalfopristinm

Gentamicin Chloramphenicolb

Erythomycinb

Tetracyclinec

Rifampind

(These agents may betested for VRE)

q

Netilmicin

Tetracyclinec Rifampind

Tobramycin Tetracyclinec

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Enterobacteriaceaeg Pseudomonas aeruginosaj

Staphylococcus spp. Enterococcus spp.n

Ampicillin g Ceftazidime Oxacillinl Penicillino or ampicillinCefazolina

Cephalothina

Gentamicin Penicillinl

Gentamicin Mezlocillin or ticarcillin

Piperacillin

Carbenicillin Carbenicillin Lomefloxacin ornorfloxacin

CiprofloxacinLevofloxacinNorfloxacin

CinoxacinLomefloxacin or

norfloxacin orofloxacin

Lomefloxacin ornorfloxacin orofloxacin

Nitrofurantoin Nitrofurantoin

Gatifloxacin

Loracarbef Sulfisoxazole Tetracyclinec

Nitrofurantoin

SulfisoxazoleTrimethoprim Trimethoprim

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©Clinical and Laboratory Standards Institute. All rights reserved.

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For Use With M2-A8–Disk Diffusion M100-S15Table 1. (Continued)

Acinetobacter spp.j,k

Burkholderia cepaciaj,k

Stenotrophomonas maltophiliaj,k

Ceftazidime Trimethoprim-sulfamethoxazole

Trimethoprim-sulfamethoxazole

ImipenemMeropenem

GR

OU

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AmikacinGentamicinTobramycin

Ceftazidime Levofloxacin

Meropenem Minocycline

Minocycline

Ampicillin-sulbactamPiperacillin-tazobactamTicarcillin-clavulanate

Cefepime

CefotaximeCeftriaxone

CiprofloxacinGatifloxacinLevofloxacin

DoxycyclineMinocyclineTetracycline

MezlocillinPiperacillinTicarcillin


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Table 1. (Continued)

NOTE 1: Selection of the most appropriate antimicrobial agents to test and to report is a decision madebest by each clinical laboratory in consultation with the infectious disease practitioners and thepharmacy, as well as the pharmacy and therapeutics and infection control committees of themedical staff. The lists for each organism group comprise agents of proven efficacy that showacceptable in vitro test performance. Considerations in the assignment of agents to Groups A, B,C, and U include clinical efficacy, prevalence of resistance, minimizing emergence of resistance,cost, and current consensus recommendations for first-choice and alternative drugs, in addition tothe specific comments in footnotes ”e” and “f.” Tests on selected agents may be useful for infectioncontrol purposes.

NOTE 2: The boxes in the table designate clusters of comparable agents that need not be duplicatedin testing, because interpretive results are usually similar and clinical efficacy is comparable. Inaddition, an “or” designates a related group of agents that has an almost identical spectrum ofactivity and interpretive results, and for which cross-resistance and susceptibility are nearlycomplete. Therefore, usually only one of the agents within each selection box (cluster or relatedgroup) need be selected for testing. Agents that are reported must be tested, unless reportingbased on testing another agent provides a more accurate result (e.g., susceptibility of staphylococcito cefazolin or cephalothin based on oxacillin testing), and they should match those included in thehospital formulary; or else the report should include footnotes indicating the agents that usuallyshow comparable interpretive results. Unexpected results should be considered for reporting (e.g.,resistance of Enterobacteriaceae to third-generation cephalosporins or imipenem).

NOTE 3: Information in boldface type is considered tentative for one year.

FootnotesGeneral Comments

a. Cephalothin can be used to represent cephalothin, cephapirin, cephradine, cephalexin, cefaclor, andcefadroxil. Cefazolin, cefuroxime, cefpodoxime, cefprozil, and loracarbef (urinary isolates only) may betested individually, because some isolates may be susceptible to these agents when resistant tocephalothin.

b. Not routinely reported on organisms isolated from the urinary tract.

c. Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline andminocycline. However, some organisms that are intermediate or resistant to tetracycline may besusceptible to doxycycline or minocycline or both.

d. Rx: Rifampin should not be used alone for chemotherapy.

e. Group B represents agents that may warrant primary testing but which should be reported onlyselectively, such as when the organism is resistant to agents of the same class in Group A. Otherindications for reporting the result might include selected specimen sources (e.g., third-generationcephalosporin for isolates of enteric bacteria from cerebrospinal fluid or trimethoprim-sulfamethoxazolefor urinary tract isolates); stated allergy or intolerance, or failure to respond to an agent in Group A;polymicrobial infections; infections involving multiple sites with different microorganisms; or reports toinfection control as an epidemiologic aid.

“Warning”: The following antimicrobial agents should not be routinely reported forbacteria isolated from the CSF and which are included in this document. Theseantimicrobial agents are not the drugs of choice and may not be effective for treating CSFinfections caused by these organisms (i.e., the bacteria included in Tables 2A to 2I):

agents administered by oral route only1st- and 2nd-generation cephalosporins (except cefuroxime sodium)

clindamycinmacrolides

tetracyclinesfluoroquinolones

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f. Group C represents alternative or supplemental antimicrobial agents that may require testing in thoseinstitutions that harbor endemic or epidemic strains resistant to one or more of the primary drugs(especially in the same class, e.g., β-lactams or aminoglycosides), or for treatment of unusual organisms(e.g., chloramphenicol for some Pseudomonas spp., and chloramphenicol, erythromycin, rifampin, andtetracycline for some vancomycin-resistant enterococci), or reporting to infection control as anepidemiologic aid.

Enterobacteriaceae

g. For fecal isolates of Salmonella and Shigella spp., only ampicillin, a quinolone, and trimethoprim-sulfamethoxazole should be tested and reported routinely. In addition, chloramphenicol and a third-generation cephalosporin should be tested and reported for extraintestinal isolates of Salmonella spp.

h. Cefotaxime and ceftriaxone should be tested and reported on isolates from CSF in place of cephalothinand cefazolin.

i. Strains of Klebsiella spp. and E. coli that produce ESBLs may be clinically resistant to therapy withpenicillins, cephalosporins, or aztreonam, despite apparent in vitro susceptibility to some of these agents.Some of these strains will show zones of inhibition below the normal susceptible population but above thestandard breakpoints for certain extended-spectrum cephalosporins or aztreonam; such strains may bescreened for potential ESBL production by using the screening breakpoints listed in the table at the endof Table 2A, Initial Screen Test. Other strains may test intermediate or resistant by standard breakpointsto one or more of these agents. In all strains with ESBLs, the zone diameters for one or more of theextended-spectrum cephalosporins should increase in the presence of clavulanic acid as described at theend of Table 2A, Phenotypic Confirmatory Test. For all confirmed ESBL-producing strains, the testinterpretation should be reported as resistant for all penicillins, cephalosporins, and aztreonam. (SeeGlossary I for specific agents included in the antimicrobial class, penicillins, and antimicrobial subclass,cephalosporins.)

Pseudomonas aeruginosa, Acinetobacter spp., Burkholderia cepacia, and Stenotrophomonasmaltophilia

j. Non-Enterobacteriaceae except for P. aeruginosa, Acinetobacter spp., B. cepacia, and S. maltophiliashould be tested by the dilution method (see M7).

k. Other agents may be approved for therapy but their performance has not been sufficientlystudied to establish disk diffusion breakpoints.

Staphylococcus spp.

l. Penicillin-susceptible staphylococci are also susceptible to other penicillins, cephems, and carbapenemsapproved for use by the FDA for staphylococcal infections. Penicillin-resistant, oxacillin-susceptible strainsare resistant to penicillinase-labile penicillins but susceptible to other penicillinase-stable penicillins, β-lactam/β-lactamase inhibitor combinations, relevant cephems, and carbapenems. (See Glossary I forspecific agents included in the antimicrobial class or antimicrobial subclass indicated). Oxacillin-resistantstaphylococci are resistant to all currently available β-lactam antibiotics. Thus, susceptibility or resistanceto a wide array of β-lactam antibiotics may be deduced from testing only penicillin and oxacillin. Routinetesting of other penicillins, β-lactamase inhibitor combinations, cephems, and carbapenems is notadvised.

m.For reporting against methicillin-susceptible Staphylococcus aureus.

Enterococcus spp.

n. Warning: For Enterococcus spp., cephalosporins, aminoglycosides (except for high-level resistancescreening), clindamycin, and trimethoprim-sulfamethoxazole may appear active in vitro but are noteffective clinically, and isolates should not be reported as susceptible.

o. Penicillin susceptibility may be used to predict the susceptibility to ampicillin, amoxicillin, ampicillin-


28

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e 1

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usio

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sulbactam, amoxicillin-clavulanic acid, piperacillin, and piperacillin-tazobactam for non-β-lactamase-producing enterococci. For blood and cerebrospinal fluid isolates, a β-lactamase test is alsorecommended. Rx: Combination therapy of penicillin or ampicillin, plus an aminoglycoside, is usuallyindicated for serious enterococcal infections, such as endocarditis.

p. Rx: If vancomycin is used for serious enterococcal infections, such as endocarditis, combined therapy withan aminoglycoside is usually indicated.

q. Because of limited alternatives, chloramphenicol, erythromycin, tetracycline (or doxycycline orminocycline), and rifampin may be tested for vancomycin-resistant enterococci (VRE), and consultationwith an infectious disease practitioner is recommended.

r. For reporting against vancomycin-resistant Enterococcus faecium.

s. For reporting against vancomycin-susceptible Enterococcus faecalis.



29©Clinical and Laboratory Standards Institute. All rights reserved.

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30

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Table 1A. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should Be Consideredfor Routine Testing and Reporting on Fastidious Organisms by Clinical Microbiology Laboratories

GR

OU

PA

PRIM

ARY

TEST

A

ND

REP

OR

THaemophilus spp.e Neisseria

gonorrhoeaeStreptococcus pneumoniae j

Streptococcus spp.Other ThanStreptococcus pneumoniae

Ampicillin e, g Erythromycina Erythromycina,o,r


Penicillin (oxacillin disk)k Penicillinm, n, p or ampicillinn, p


Azithromycinf orclarithromycinf

Cefixime orcefotaxime orcefpodoxime orceftizoxime orceftriaxone

ChloramphenicoloCefepime or

cefotaxime orceftriaxone

Aztreonam Linezolid

Cefaclorf or cefprozilf orloracarbef f

CefmetazoleCefotetanCefoxitinCefuroxime

Rifampinl Daptomycinn

Levofloxacinn

Ofloxacinn

Cefdinirf orcefiximef orcefpodoximef

Linezolid

Cefonicid

Cefuroxime axetilf (oral) Ciprofloxacin orgatifloxacin or ofloxacin

Quinupristin-dalfopristinq

Ciprofloxacin orgatifloxacin orlevofloxacin or lomefloxacin ormoxifloxacin orofloxacin orsparfloxacin

Gemifloxacin

Penicillini

Ertapenem orimipenem

Spectinomycin

TetracyclineRifampin

Telithromycinf

Tetracyclined

GR

OU

PC

c

SUPP

LEM

ENTA

LR

EPO

RT

SELE

CTI

VELY

Cefotaximee orceftazidimee orceftizoximee orceftriaxonee

Clindamycin Chloramphenicolo

Gatifloxacin GemifloxacinLevofloxacinMoxifloxacinOfloxacinSparfloxacin

Cefuroxime sodium(parenteral)

Telithromycin

Tetracyclined

Chloramphenicole

Meropeneme,h Vancomycink

Clindamycino,r

Vancomycin

GR

OU

PB

b

PRIM

ARY

TEST

R

EPO

RT

SELE

CTI

VELY


31

Tabl

e 1A

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Table 1A. (Continued)

NOTE 1: Selection of the most appropriate antimicrobial agents to test and to report is a decision bestmade by each clinical laboratory in consultation with the infectious disease practitioners and thepharmacy, as well as the pharmacy and therapeutics and infection control committees of themedical staff. The lists for each organism group comprise agents of proven efficacy that showacceptable in vitro test performance. Considerations in the assignment of agents to Groups A, B,and C include clinical efficacy, prevalence of resistance, minimizing emergence of resistance, cost,and current consensus recommendations for first-choice and alternative drugs, in addition to thespecific comments in footnotes “b” and “c.” Tests on selected agents may be useful for infectioncontrol purposes.

NOTE 2: The boxes in the table designate clusters of comparable agents that need not be duplicated intesting, because interpretive results are usually similar and clinical efficacy is comparable. Inaddition, an “or” designates a related group of agents that has an almost identical spectrum ofactivity and interpretive results, and for which cross-resistance and susceptibility are nearlycomplete. Therefore, usually only one of the agents within each selection box (cluster or relatedgroup) need be selected for testing. Agents reported must be tested, unless reporting based ontesting another agent provides a more accurate result, and they should match those included in thehospital formulary; or else the report should include footnotes indicating the agents that usuallyhave comparable interpretive results. Unexpected results should be considered for reporting.


Footnotes

General Comments

a. Susceptibility and resistance to azithromycin, clarithromycin, and dirithromycin can be predicted bytesting erythromycin.

b. Group B represents agents that may warrant primary testing but which should be reported onlyselectively, such as when the organism is resistant to agents of the same class in Group A. Otherindications for reporting the result might include selected specimen sources (e.g., third-generationcephalosporin for isolates of Haemophilus influenzae from CSF); stated allergy or intolerance, orfailure to respond to an agent in Group A; polymicrobial infections; infections involving multiple siteswith different microorganisms; or reports to infection control as an epidemiologic aid.

c. Group C represents alternative or supplemental antimicrobial agents that may require testing in thoseinstitutions that harbor endemic or epidemic strains resistant to one or more of the primary drugs(especially in the same class, e.g., β-lactams), or for treatment of unusual organisms, or reporting toinfection control as an epidemiologic aid.

“Warning”: The following antimicrobial agents should not be routinely reported forbacteria isolated from the CSF and which are included in this document. Theseantimicrobial agents are not the drugs of choice and may not be effective for treatingCSF infections caused by these organisms (i.e., the bacteria included in Tables 2A to2I):





32

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d. Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline andminocycline.

Haemophilus spp.

e. Only results of testing with ampicillin, one of the third-generation cephalosporins, chloramphenicol,and meropenem should be reported routinely with CSF isolates of H. influenzae.

f. Amoxicillin-clavulanic acid, azithromycin, clarithromycin, cefaclor, cefprozil, loracarbef, cefdinir,cefixime, cefpodoxime, cefuroxime axetil, and telithromycin are oral agents that may be used asempiric therapy for respiratory tract infections due to Haemophilus spp. The results of susceptibilitytests with these antimicrobial agents are often not useful for management of individual patients.However, susceptibility testing of Haemophilus spp. with these compounds may be appropriate forsurveillance or epidemiologic studies.

g. The results of ampicillin susceptibility tests should be used to predict the activity of amoxicillin. Themajority of isolates of H. influenzae that are resistant to ampicillin and amoxicillin produce a TEM-typeβ-lactamase. In most cases, a direct β-lactamase test can provide a rapid means of detectingampicillin and amoxicillin resistance.

h. Clinical indications and relevant pathogens include bacterial meningitis and concurrent bacteremia inassociation with meningitis caused by H. influenzae (β-lactamase and non-β-lactamase-producingstrains).

Neisseria gonorrhoeae

i. A β-lactamase test will detect one form of penicillin resistance in N. gonorrhoeae and also may be usedto provide epidemiologic information. Strains with chromosomally mediated resistance can bedetected only by additional susceptibility testing, such as the disk diffusion method or the agar dilutionMIC method.

Streptococcus pneumoniae

j. Amoxicillin, ampicillin, cefepime, cefotaxime, ceftriaxone, cefuroxime, imipenem, and meropenem maybe used to treat pneumococcal infections; however, reliable disk diffusion susceptibility tests withthese agents do not yet exist. Their in vitro activity is best determined using an MIC method (see M7).

k. Penicillin, cefotaxime or ceftriaxone, and meropenem should be tested by a reliable MIC method (suchas that described in CLSI/NCCLS document M7) and reported routinely with CSF isolates of S.pneumoniae. Such isolates should also be tested against vancomycin using the MIC or disk method.With isolates from other sites, the oxacillin disk screening test may be used. If the oxacillin zone sizeis ≤ 19 mm, penicillin and cefotaxime or ceftriaxone MICs should be determined.

l. Rx: Rifampin should not be used alone for chemotherapy.

Streptococcus spp.

m. Viridans streptococci isolated from blood and normally sterile body sites (e.g., cerebrospinal fluid,blood, bone) should be tested for penicillin or ampicillin susceptibility using an MIC method.

n. Disk diffusion interpretive criteria for penicillin, ampicillin, levofloxacin, ofloxacin, and daptomycin arefor reporting against isolates of beta-hemolytic streptococci only.


33

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o. Not routinely reported on organisms isolated from the urinary tract.

p. Susceptibility testing of penicillins and other β-lactams approved by FDA for treatment ofStreptococcus pyogenes or Streptococcus agalactiae is not necessary for clinical purposes and neednot be done routinely, since as with vancomycin, resistant strains have not been recognized.Interpretive criteria are provided for pharmaceutical development, epidemiology, or monitoring foremerging resistance. Any strain found to be nonsusceptible should be referred to a referencelaboratory for confirmation.

q. Report against S. pyogenes.

r. Rx: Recommendations for intrapartum prophylaxis for Group B streptococci are penicillin orampicillin. While cefazolin is recommended for penicillin-allergic women at low risk foranaphylaxis, those at high risk for anaphylaxis may receive clindamycin or erythromycin.Group B streptococci are susceptible to ampicillin, penicillin, and cefazolin, but may beresistant to clindamycin and/or erythromycin. When a Group B streptococcus is isolated froma pregnant woman with severe penicillin allergy (high risk for anaphylaxis), clindamycin anderythromycin should be tested and reported.

Min

imal

QC

Rec

omm

enda

tions

(See

Tab

le 3

for a

ccep

tabl

e Q

C ra

nges

.)

Esch

eric

hia

coli

ATC

C®

2592

2Es

cher

ichi

a co

liAT

CC

®35

218

(for β

-lact

am/β

-lact

amas

e in

hibi

tor

com

bina

tions

)


34

Tabl

e 2A

Ente

roba

cter

iace

aeM

2-D

isk

Diff

usio

n


Tabl

e 2A

. Zo

ne D

iam

eter

Inte

rpre

tive

Stan

dard

s an

d Eq

uiva

lent

Min

imal

Inhi

bito

ry C

once

ntra

tion

(MIC

) Bre

akpo

ints

for

Ente

roba

cter

iace

ae

Gen

eral

Com

men

ts

(1)

For

feca

l iso

late

s of

Sal

mon

ella

and

Shig

ella

spp.

onl

y am

pici

llin,

a q

uino

lone

, and

trim

etho

prim

-sul

fam

etho

xazo

le s

houl

d be

test

ed a

nd re

porte

d ro

utin

ely.

Inad

ditio

n, c

hlor

amph

enic

ol a

nd a

third

-gen

erat

ion

ceph

alos

porin

sho

uld

be te

sted

and

repo

rted

for e

xtra

inte

stin

al is

olat

es o

f Sal

mon

ella

spp.

NO

TE:I

nfor

mat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.

Test

/Rep

ort

Gro

up

Ant

imic

robi

al A

gent

Dis

k C

onte

ntZo

ne D

iam

eter

, N

eare

st W

hole

mm

Equi

vale

nt M

IC

Bre

akpo

ints

(µµg/

mL)

C

omm

ents

RI

SR

S

PEN

ICIL

LIN

SA

Am

pici

llin

10 µ

g≤

13

14-1

6 ≥

17

≥32

≤

8 (2

) C

lass

repr

esen

tativ

e fo

ram

pici

llin

and

amox

icill

in.

B B B

Mez

loci

llin

or

pipe

raci

llin

Tica

rcill

in

75 µ

g10

0 µg

75 µ

g

≤17

≤17

≤14

18-2

018

-20

15-1

9

≥21

≥21

≥20

≥12

8≥

128

≥12

8

≤16

≤16

≤16

UC

arbe

nici

llin

100

µg≤

1920

-22

≥23

≥64

≤16

UM

ecill

inam

10

µg

≤11

12-1

4 ≥

15

≥32

≤

8 (3

) Fo

r use

aga

inst

E. c

oli u

rinar

ytra

ct is

olat

es o

nly.

ββ -

LAC

TAM

/ββ-L

AC

TAM

ASE

INH

IBIT

OR

CO

MB

INAT

ION

SB B B B

Am

oxic

illin

-cla

vula

nic

acid

or

ampi

cilli

n-su

lbac

tam

Pip

erac

illin

-tazo

bact

amTi

carc

illin

-cla

vula

nic

acid

20/1

0 µg

10/1

0 µg

100/

10 µ

g75

/10

µg

≤13

≤11

≤17

≤14

14-1

712

-14

18-2

015

-19

≥18

≥15

≥21

≥20

≥32

/16

≥32

/16

≥12

8/4

≥12

8/2

≤8/

4≤

8/4

≤16

/4≤

16/2

Test

ing

Con

ditio

ns

Med

ium

:M

uelle

r-H

into

n ag

ar

Inoc

ulum

:G

row

th m

etho

d or

dire

ct c

olon

y su

spen

sion

, eq

uiva

lent

to a

0.5

McF

arla

nd s

tand

ard

Incu

batio

n:35

° C ±

2 de

gree

s; a

mbi

ent a

ir; 1

6 to

18

hour

s



Tabl

e 2A

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

tsR

I

S R

S

CEP

HEM

S (P

AR

ENTE

RA

L) (

Incl

udin

g ce

phal

ospo

rins

I, II,

III,

and

IV. P

leas

e re

fer

to G

loss

ary

I.)

(4)

WA

RN

ING

:For

Sal

mon

ella

spp.

and

Shi

gella

spp.

, firs

t- an

d se

cond

-ge

nera

tion

ceph

alos

porin

s m

ay a

ppea

r act

ive

in v

itro

but a

re n

ot e

ffect

ive

clin

ical

ly a

nd s

houl

d no

t be

repo

rted

as s

usce

ptib

le.

(5)

Stra

ins

of K

lebs

iella

spp

. and

E. c

olit

hat p

rodu

ce e

xten

ded-

spec

trum

beta

-lact

amas

e (E

SB

Ls)

may

be

cl

inic

ally

re

sist

ant

to

ther

apy

with

peni

cilli

ns,

ceph

alos

porin

s,

or

aztre

onam

, de

spite

ap

pare

nt

in

vitro

susc

eptib

ility

to

som

e of

the

se a

gent

s. S

ome

of t

hese

stra

ins

will

sho

wzo

nes

of in

hibi

tion

belo

w th

e no

rmal

sus

cept

ible

pop

ulat

ion

but a

bove

the

stan

dard

bre

akpo

ints

for

cer

tain

ext

ende

d-sp

ectru

m c

epha

losp

orin

s or

aztre

onam

. S

uch

stra

ins

shou

ld

be

scre

ened

fo

r po

tent

ial

ES

BL

prod

uctio

n by

usi

ng th

e E

SB

Lsc

reen

ing

brea

kpoi

nts

liste

d at

the

end

ofth

is

tabl

e be

fore

re

porti

ng

resu

lts

for

peni

cilli

ns,

exte

nded

-spe

ctru

mce

phal

ospo

rins,

or

aztre

onam

. O

ther

stra

ins

may

tes

t in

term

edia

te o

rre

sist

ant b

y st

anda

rd b

reak

poin

ts to

one

or

mor

e of

thes

e ag

ents

. In

all

stra

ins

with

ES

BLs

, the

zon

e di

amet

ers

for o

ne o

r mor

e of

the

exte

nded

-sp

ectru

m c

epha

losp

orin

s or

azt

reon

am s

houl

d in

crea

se in

the

pres

ence

of

clav

ulan

ic a

cid

as d

eter

min

ed in

phe

noty

pic

conf

irmat

ory

test

ing.

Fo

r al

lco

nfirm

ed

ES

BL-

prod

ucin

g st

rain

s,

the

test

in

terp

reta

tion

shou

ld

bere

porte

d as

res

ista

nt f

or a

ll pe

nici

llins

, ce

phal

ospo

rins,

and

azt

reon

am.

(See

tab

le l

ocat

ed a

t th

e en

d of

thi

s ta

ble

for

ES

BL

scre

enin

g an

dco

nfirm

ator

y te

sts.

R

efer

to

glos

sary

for

def

initi

ons

of p

enic

illin

s an

dce

phal

ospo

rins.

) Th

e de

cisi

on t

o pe

rform

ES

BL

scre

enin

g te

sts

on a

llur

ine

isol

ates

sho

uld

be m

ade

on a

n in

stitu

tiona

l ba

sis,

con

side

ring

prev

alen

ce, t

hera

py, a

nd in

fect

ion

cont

rol i

ssue

s.

(6) R

outin

e sc

reen

ing

ofPr

oteu

s m

irabi

lisfo

r ESB

Lpr

oduc

tion

is n

otre

com

men

ded.

How

ever

, whe

n it

is d

eem

ed c

linic

ally

rele

vant

(e.g

., a

bact

erem

ic i

sola

te),

the

ESB

Lsc

reen

tes

ting

zone

s, c

efta

zidi

me

(≤≤22

mm

), ce

fota

xim

e (≤≤

27 m

m),

or c

efpo

doxi

me

(≤≤17

mm

) w

illid

entif

y pr

esum

ptiv

e ES

BL

prod

uctio

n. T

he p

heno

typi

c co

nfirm

ator

yte

st u

sing

cef

tazi

dim

e an

d ce

fota

xim

e al

one

and

in c

ombi

natio

n w

ithcl

avul

anic

ac

id

can

conf

irm

ES

BL-

prod

ucin

g st

rain

s.

For

all

conf

irm

ed

ESB

L-pr

oduc

ing

P.m

irabi

lis,

the

test

in

terp

reta

tion

shou

ld b

e re

port

ed a

s re

sist

ant

for

all

peni

cilli

ns,

ceph

alos

porin

s,an

d az

treo

nam

.

(7)

Ente

roba

cter

, Citr

obac

ter,

and

Serra

tiam

ay d

evel

op re

sist

ance

dur

ing

prol

onge

d th

erap

y w

ith

third

-gen

erat

ion

ceph

alos

porin

s.

Ther

efor

e,is

olat

es th

at a

re in

itial

ly s

usce

ptib

le m

ay b

ecom

e re

sist

ant w

ithin

thre

e to

four

day

s af

ter

initi

atio

n of

the

rapy

. Te

stin

g of

rep

eat

isol

ates

may

be

war

rant

ed.

A AC

efaz

olin

Cep

halo

thin

30

µg

30 µ

g≤

14≤

14

15-1

7 15

-17

≥18

≥

18

≥32

≥32

≤8

≤8

(8) C

epha

loth

in c

an b

e us

ed to

pre

dict

act

ivity

of c

epha

loth

in, c

epha

pirin

,ce

phra

dine

, ce

phal

exin

, ce

facl

or,

and

cefa

drox

il. C

efaz

olin

, ce

furo

xim

e,ce

fpod

oxim

e, c

efpr

ozil,

and

lor

acar

bef

(urin

ary

isol

ates

onl

y) m

ay b

ete

sted

indi

vidu

ally,

bec

ause

som

e is

olat

es m

ay b

e su

scep

tible

to

thes

eag

ents

whe

n re

sist

ant t

o ce

phal

othi

n.

T abl

e 2A

Ente

roba

cter

iace

aeM

2-D

isk

Diff

usio

n


36

Tabl

e 2A

Ente

roba

cter

iace

aeM

2-D

isk

Diff

usio

n


Tabl

e 2A

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

ts

R

I S

R

S C

EPH

EMS

(PA

REN

TER

AL)

(Con

tinue

d)B B B

Cef

aman

dole

or

cefo

nici

d or

cefu

roxi

me

sodi

um(p

aren

tera

l)

30 µ

g30

µg

30 µ

g

≤ 14

≤

14

≤ 14

15-1

715

-17

15-1

7

≥ 18

≥ 18

≥ 18

≥ 32

≥ 32

≥ 32

≤ 8

≤ 8

≤ 8

BC

efep

ime

30 µ

g≤

1415

-17

≥ 18

≥ 32

≤ 8

B B B B

Cef

met

azol

eC

efop

eraz

one

Cef

otet

anC

efox

itin

30 µ

g75

µg

30 µ

g30

µg

≤12

≤15

≤12

≤14

13-1

516

-20

13-1

515

-17

≥ 16

≥ 21

≥ 16

≥ 18

≥ 6

4≥

64

≥ 6

4≥

32

≤ 16

≤ 16

≤ 16

≤ 8

B B B

Cef

otax

ime

orce

ftizo

xim

e or

ceftr

iaxo

ne

30 µ

g30

µg

30 µ

g

≤ 14

≤

14≤

13

15-2

215

-19

14-2

0

≥ 23

≥ 20

≥ 21

≥ 6

4≥

32

≥ 6

4

≤ 8

≤ 8

≤ 8

(9) C

efot

axim

e an

d ce

ftria

xone

sho

uld

be te

sted

and

repo

rted

on is

olat

es fr

om C

SF

in p

lace

of c

epha

loth

in a

nd c

efaz

olin

.

See

com

men

t (5)

.C

Cef

tazi

dim

e30

µg

≤ 14

15-1

7 ≥

18

≥ 3

2≤

8S

ee c

omm

ent (

5).

OM

oxal

acta

m30

µg

≤ 14

15

-22

≥ 23

≥ 6

4≤

8C

EPH

EMS

(OR

AL)

BC

efur

oxim

e ax

etil

(ora

l)30

µg

≤ 14

15

-22

≥ 23

≥ 3

2≤

4U

Lora

carb

ef30

µg

≤ 14

15

-17

≥ 18

≥ 3

2≤

8(1

0) B

ecau

se c

erta

in s

train

s of

Citr

obac

ter,

Prov

iden

cia,

and

Ente

roba

cter

spp.

hav

e be

en re

porte

d to

giv

e fa

lse-

susc

eptib

lere

sults

with

cef

dini

r an

d lo

raca

rbef

dis

ks,

stra

ins

of t

hese

gene

ra s

houl

d no

t be

test

ed a

nd re

porte

d w

ith th

ese

disk

s.

OC

efac

lor

30 µ

g ≤

14

15-1

7≥

18≥

32≤

8

OC

efdi

nir

5 µg

≤

16

17-1

9≥

20≥

4≤

1S

ee c

omm

ent (

10).

OC

efix

ime

5 µg

≤

1516

-18

≥ 19

≥ 4

≤

1(1

1) N

ot a

pplic

able

for t

estin

g M

orga

nella

spp.

OC

efpo

doxi

me

10 µ

g ≤

1718

-20

≥ 21

≥ 8

≤

2S

ee c

omm

ents

(5) a

nd (1

1).

OC

efpr

ozil

30 µ

g ≤

1415

-17

≥ 18

≥ 3

2≤

8(1

2) B

ecau

se c

erta

in s

train

s of

Pro

vide

ncia

spp.

hav

e be

enre

porte

d to

giv

e fa

lse-

susc

eptia

ble

resu

lts w

ith c

efpr

oxil

disk

s,st

rain

s of

this

gen

us s

houl

d no

t be

test

ed a

nd re

porte

d w

ith th

isdi

sk.

Inv.

Cef

etam

et10

µg

≤ 14

15-1

7≥

18≥

16≤

4S

ee c

omm

ent (

11).

Inv.

Cef

tibut

en30

µg

≤ 17

18-2

0≥

21≥

32≤

8(1

3) In

dica

ted

for u

rine

isol

ates

onl

y.C

AR

BA

PEN

EMS

B B B

Erta

pene

mIm

ipen

em o

rm

erop

enem

10 µ

g 10

µg

10 µ

g

≤ 15

≤ 1

3 ≤

13

16-1

814

-15

14-1

5

≥ 19

≥ 16

≥ 16

≥ 8

≥ 16

≥ 16

≤ 2

≤ 4

≤ 4

MO

NO

BA

CTA

MS

CA

ztre

onam

30 µ

g ≤

15

16-2

1≥

22≥

32≤

8S

ee c

omm

ent (

5).


37

Tabl

e 2A

Ente

roba

cter

iace

aeM

2-D

isk

Diff

usio

n


Tabl

e 2A

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

ts

R

I S

R

S A

MIN

OG

LYC

OSI

DES

(14)

WA

RN

ING

:Fo

r Sa

lmon

ella

spp.

and

Shi

gella

spp.

, am

inog

lyco

side

s m

ay a

ppea

r act

ive

in v

itro

but

are

not e

ffect

ive

clin

ical

ly a

nd s

houl

d no

t be

repo

rted

as s

usce

ptib

le.

AG

enta

mic

in

10 µ

g ≤

1213

-14

≥15

≥8

≤4

BA

mik

acin

30 µ

g≤

1415

-16

≥17

≥32

≤16

C

Kan

amyc

in30

µg

≤13

14-1

7≥

18≥

25≤

6C

N

etilm

icin

30 µ

g≤

1213

-14

≥15

≥32

≤12

C

Tobr

amyc

in10

µg

≤12

13-1

4≥

15≥

8≤

4O

Stre

ptom

ycin

10 µ

g≤

1112

-14

≥15

--

TETR

AC

YCLI

NES

C

Tetra

cycl

ine

30 µ

g≤

1415

-18

≥19

≥16

≤4

(15)

Org

anis

ms

that

are

sus

cept

ible

to

tetra

cycl

ine

are

also

con

side

red

susc

eptib

le t

o do

xycy

clin

e an

dm

inoc

yclin

e.

How

ever

, so

me

orga

nism

s th

at a

rein

term

edia

te

or

resi

stan

t to

te

tracy

clin

e m

ay

besu

scep

tible

to d

oxyc

yclin

e or

min

ocyc

line

or b

oth.

OD

oxyc

yclin

e30

µg

≤12

13-1

5≥

16≥

16≤

4O

Min

ocyc

line

30 µ

g≤

1415

-18

≥19

≥16

≤4

FLU

OR

OQ

UIN

OLO

NES

(1

6) F

luor

oqui

nolo

ne-s

usce

ptib

le s

train

s of

Sal

mon

ella

that

test

res

ista

nt to

nal

idix

ic a

cid

may

be

asso

ciat

edw

ith

clin

ical

fa

ilure

or

de

laye

d re

spon

se

influ

oroq

uino

lone

-trea

ted

patie

nts

with

ex

train

test

inal

salm

onel

losi

s. E

xtra

inte

stin

al i

sola

tes

of S

alm

onel

lash

ould

als

o be

tes

ted

for

resi

stan

ce t

o na

lidix

ic a

cid.

For

isol

ates

tha

t te

st s

usce

ptib

le t

o flu

oroq

uino

lone

san

d re

sist

ant t

o na

lidix

ic a

cid,

the

phys

icia

n sh

ould

be

info

rmed

tha

t th

e is

olat

e m

ay n

ot b

e er

adic

ated

by

fluor

oqui

nolo

ne

treat

men

t. A

cons

ulta

tion

with

an

infe

ctio

us d

isea

se p

ract

ition

er is

reco

mm

ende

d.

B BC

ipro

floxa

cin

or

levo

floxa

cin

5 µg

5 µg

≤

15≤

13

16-2

014

-16

≥21

≥17

≥4

≥8

≤1

≤2

UG

atifl

oxac

in5

µg≤

1415

-17

≥18

≥8

≤2

BG

emifl

oxac

in5

µg≤

1516

-19

≥20

≥1

≤0.

25(1

7) F

DA

-app

rove

d fo

r Kle

bsie

lla p

neum

onia

e.

U U U

Lom

eflo

xaci

n or

norfl

oxac

in o

rof

loxa

cin

10 µ

g10

µg

5 µg

≤18

≤12

≤12

19-2

113

-16

13-1

5

≥22

≥17

≥16

≥8

≥16

≥8

≤2

≤4

≤2

OE

noxa

cin

10 µ

g≤

1415

-17

≥18

≥8

≤2

OG

repa

floxa

cin

5 µg

≤14

15-1

7≥

18≥

4≤

1In

v.Fl

erox

acin

5 µg

≤15

16-1

8≥

19≥

8≤

2


38

Tabl

e 2A

Ente

roba

cter

iace

aeM

2-D

isk

Diff

usio

n


Tabl

e 2A

. (C

ontin

ued)

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntD

isk

Con

tent

Zone

Dia

met

er,

Nea

rest

Who

le m

mEq

uiva

lent

MIC

Bre

akpo

ints

(µµg/

mL)

Com

men

tsR

IS

RS

QU

INO

LON

ES

UC

inox

acin

100

µg≤

1415

-18

≥19

≥64

≤16

ON

alid

ixic

aci

d30

µg

≤13

14-1

8≥

19≥

32≤

8S

ee c

omm

ent (

13)

(18)

In a

dditi

on to

test

ing

urin

e is

olat

es, n

alid

ixic

aci

dm

ay b

e us

ed t

o te

st f

or r

educ

ed f

luor

oqui

nolo

nesu

scep

tibili

ty

in

isol

ates

fro

m

patie

nts

with

extra

inte

stin

al S

alm

onel

la i

nfec

tions

. S

ee c

omm

ent

(16)

.FO

LATE

PAT

HW

AYIN

HIB

ITO

RS

BTr

imet

hopr

im-

su

lfam

etho

xazo

le1.

25/

23.7

5 µg

≤10

11-1

5≥

16≥

8/15

2≤

2/38

US

ulfo

nam

ides

250

or30

0 µg

≤12

13-1

6≥

17≥

350

≤

100

(19)

The

sul

fisox

azol

e di

sk c

an b

e us

ed to

repr

esen

tan

y of

th

e cu

rren

tly

avai

labl

e su

lfona

mid

epr

epar

atio

ns.

UTr

imet

hopr

im5

µg≤

1011

-15

≥16

≥16

≤

4

PHEN

ICO

LSC

Chl

oram

phen

icol

30 µ

g≤

1213

-17

≥18

≥32

≤8

(20)

Not

rou

tinel

y re

porte

d on

iso

late

s fro

m t

heur

inar

y tra

ct.

NIT

RO

FUR

AN

TOIN

SU

Nitr

ofur

anto

in30

0 µg

≤14

15-1

6≥

17≥

128

≤32

FOSF

OM

YCIN

SU

Fosf

omyc

in20

0 µg

≤12

13-1

5≥

16≥

256

≤64

(21)

Indi

cate

d fo

r us

e ag

ains

t E. c

olio

nly.

The

200

-µg

fos

fom

ycin

dis

k co

ntai

ns 5

0 µg

of

gluc

ose-

6-ph

osph

ate.


39

Tabl

e 2A

Ente

roba

cter

iace

aeM

2-D

isk

Diff

usio

n


Footnotea. Routine screening of Proteus mirabilis for ESBL production is not recommended. However, when it is

deemed clinically relevant (e.g., a bacteremic isolate) the ESBL screen testing zones, ceftazidime (≤≤ 22mm), cefotaxime (≤≤ 27 mm), or cefpodoxime (≤≤ 17 mm) will identify presumptive ESBL production. Thephenotypic confirmatory test using ceftazidime and cefotaxime alone and in combination withclavulanic acid can confirm ESBL-producing strains. For all confirmed ESBL-producing P. mirabilis,the test interpretation should be reported as resistant for all penicillins, cephalosporins, andaztreonam.

b. Preparation of ceftazidime-clavulanic acid (30 µg/10 µg) and cefotaxime-clavulanic acid (30 µg/10 µg) disks:Using a stock solution of clavulanic acid at 1000 µg/mL (either freshly prepared or taken from small aliquots thathave been frozen at -70 °C), add 10 µL of clavulanic acid to ceftazidime (30 µg) and cefotaxime (30 µg) disks.Use a micropipette to apply the 10 µL of stock solution to the ceftazidime and cefotaxime disks within one hourbefore they are applied to the plates, allowing about 30 minutes for the clavulanic acid to absorb and the disksto be dry enough for application. Use disks immediately after preparation or discard; do not store.


Screening and Confirmatory Tests for ESBLs in Klebsiella pneumoniae, K. oxytoca, Escherichia coli, and Proteus mirabilisa

Method Initial Screen Test Phenotypic Confirmatory Test

Medium Mueller-Hinton Agar Mueller-Hinton Agar

Antimicrobial DiskConcentration

Cefpodoxime 10 µg orceftazidime 30 µg oraztreonam 30 µg orcefotaxime 30 µg orceftriaxone 30 µg

(The use of more than one antimicrobialagent for screening improves the sensitivityof detection.)

ceftazidime 30 µgceftazidime-clavulanic acidb 30/10 µgand

cefotaxime 30 µgcefotaxime-clavulanic acidb 30/10 µg

(Confirmatory testing requires use of bothcefotaxime and ceftazidime, alone and incombination with clavulanic acid.)

Inoculum

Standard disk diffusion recommendations Standard disk diffusion recommendationsIncubation conditions

Incubation length

Results Cefpodoxime zone ≤ 17 mmCeftazidime zone ≤ 22 mmAztreonam zone ≤ 27 mmCefotaxime zone ≤ 27 mmCeftriaxone zone ≤ 25 mm= may indicate ESBL production

A ≥ 5-mm increase in a zone diameter for eitherantimicrobial agent tested in combination withclavulanic acid versus its zone when tested alone =ESBL (e.g., ceftazidime zone = 16; ceftazidime-clavulanic acid zone = 21).

QC Recommendations When testing ESBL- screeningantimicrobial agents, K. pneumoniaeATCC® 700603 is provided for qualityassessment (e.g., training, competency,or test evaluation). Either strain, K. pneumoniae ATCC® 700603 or E. coliATCC® 25922, may then be used forroutine QC (e.g., weekly or daily).E. coli ATCC® 25922 (see control limits inTable 3) K. pneumoniae ATCC® 700603:

cefpodoxime zone 9-16 mmceftazidime zone 10-18 mmaztreonam zone 9-17 mmcefotaxime zone 17-25 mmceftriaxone zone 16-24 mm

When performing the ESBL confirmatory tests,K. pneumoniae ATCC® 700603 and E. coliATCC® 25922 should be tested routinely (e.g.,weekly or daily).

E. coli ATCC® 25922: ≤ 2-mm increase in zonediameter for antimicrobial agent tested aloneversus its zone when tested in combination withclavulanic acidK. pneumoniae ATCC® 700603:≥5-mm increase in ceftazidime-clavulanic acidzone diameter; ≥ 3-mm increase in cefotaxime-clavulanic acidzone diameter.


40

Tabl

e 2B

Non

-Ent

erob

acte

riace

aeM

2-D

isk

Diff

usio

n


Min

imal

QC

Rec

omm

enda

tions

(See

Tab

le 3

for a

ccep

tabl

e Q

C ra

nges

.)

Esch

eric

hia

coli

ATC

C®

2592

2Ps

eudo

mon

as a

erug

inos

aAT

CC

®27

853

Esch

eric

hia

coli

ATC

C®

3521

8 (fo

r β-la

ctam

/β-la

ctam

ase

inhi

bito

rco

mbi

natio

ns)

Test

ing

Con

ditio

ns

Med

ium

: M

uelle

r-H

into

n ag

arIn

ocul

um:

Gro

wth

met

hod

or d

irect

col

ony

susp

ensi

on,

equi

vale

nt t

o a

0.5

McF

arla

nd s

tand

ard

Incu

batio

n: 3

5 ° C

±2

degr

ees;

am

bien

t air;

16

to 1

8 ho

urs;

20

to 2

4 ho

urs

for

Sten

otro

phom

onas

mal

toph

ilia a

nd B

urkh

olde

ria c

epac

ia

Tabl

e 2B

. Zo

ne D

iam

eter

Inte

rpre

tive

Stan

dard

s an

d Eq

uiva

lent

Min

imal

Inhi

bito

ry C

once

ntra

tion

(MIC

) Bre

akpo

ints

for P

seud

omon

as

aeru

gino

sa,A

cine

toba

cter

spp.

, Ste

notr

opho

mon

as m

alto

phili

a, a

ndB

urkh

olde

ria c

epac

ia

Gen

eral

Com

men

ts

(1)

Non

-Ent

erob

acte

riace

ae o

ther

than

P. a

erug

inos

a,Ac

inet

obac

ters

pp.,

S. m

alto

philia

,and

B. c

epac

ia(S

ee c

omm

ent (

5)) s

houl

d be

test

ed b

y th

e di

lutio

n m

etho

d.(S

ee M

7 Ta

ble

2B.)

(2)

The

susc

eptib

ility

of P

. aer

ugin

osa

isol

ated

from

pat

ient

s w

ith c

ystic

fibr

osis

can

be

relia

bly

dete

rmin

ed b

y th

e di

sk m

etho

d, b

ut m

ay re

quire

ext

ende

d in

cuba

tion

up to

24

hour

s be

fore

repo

rting

as

susc

eptib

le.

(3)

P. a

erug

inos

a m

ay d

evel

op r

esis

tanc

e du

ring

prol

onge

d th

erap

y w

ith a

ll an

tibio

tics.

The

refo

re, i

sola

tes

that

are

initi

ally

sus

cept

ible

may

bec

ome

resi

stan

t with

inth

ree

to fo

ur d

ays

afte

r ini

tiatio

n of

ther

apy.

Tes

ting

of re

peat

isol

ates

may

be

war

rant

ed.

(4)

Rx:

P. a

erug

inos

ain

fect

ions

in

gran

uloc

ytop

enic

pat

ient

s an

d se

rious

inf

ectio

ns i

n ot

her

patie

nts

shou

ld b

e tre

ated

with

max

imum

dos

es o

f th

e se

lect

edan

tipse

udom

onal

pen

icill

in (c

arbo

xype

nici

llin

or u

reid

open

icill

in) o

r cef

tazi

dim

e in

com

bina

tion

with

an

amin

ogly

cosi

de.

(5)

Onl

y m

inoc

yclin

e, le

voflo

xaci

n, a

nd tr

imet

hopr

im-s

ulfa

met

hoxa

zole

may

be

repo

rted

for

S. m

alto

philia

isol

ates

. Onl

y ce

ftazi

dim

e, m

erop

enem

, min

ocyc

line,

and

trim

etho

prim

-sul

fam

etho

xazo

le m

ay b

e re

porte

d fo

rB. c

epac

iais

olat

es.

NO

TE:

Info

rmat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

tsR

I

S R

S

PEN

ICIL

LIN

SA A A

Mez

loci

llin

or

ticar

cilli

n

Pip

erac

illin

75 µ

g

75 µ

g

100

µg

≤15

≤17

≤14

≤14

≤17

≤17

-18

-20

-15

-19

-18

-20

≥16

≥21

≥15

≥20

≥18

≥21

≥12

8≥

128

≥12

8≥

128

≥12

8≥

128

≤64

≤16

≤64

≤16

≤64

≤16

For P

. aer

ugin

osa

For A

cine

toba

cter

spp.

For P

. aer

ugin

osa

For A

cine

toba

cter

spp.

For P

. aer

ugin

osa

For A

cine

toba

cter

spp.

UC

arbe

nici

llin

100

µg≤

13≤

1914

-16

20-2

2≥

17≥

23≥

512

≥64

≤12

8≤

16Fo

r P. a

erug

inos

aFo

r Aci

neto

bact

ersp

p.O

Azl

ocill

in75

µg

≤17

- ≥

18≥

128

≤64

For P

. aer

ugin

osa


41

Tabl

e 2B

Non

-Ent

erob

acte

riace

aeM

2-D

isk

Diff

usio

n


Tabl

e 2B

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

tsR

I

S R

S

ββ -LA

CTA

M/ββ

-LA

CTA

MA

SE IN

HIB

ITO

R C

OM

BIN

ATIO

NS

OA

mpi

cilli

n-su

lbac

tam

10/1

0 µg

≤11

12-1

4≥

15≥

32/1

6≤

8/4

(6) M

ay b

e re

porte

d fo

r Aci

neto

bact

ersp

p. re

sist

ant

to o

ther

age

nts.

OP

iper

acill

in-ta

zoba

ctam

100/

10 µ

g10

0/10

µg

≤17

≤17

-18

-20

≥18

≥21

≥12

8/4

≥12

8/4

≤64

/4≤

16/4

For P

. aer

ugin

osa

For A

cine

toba

cter

spp.

OTi

carc

illin

-cla

vula

nic

acid

75/1

0 µg

75/1

0 µg

≤14

≤14

-15

-19

≥15

≥20

≥12

8/2

≥12

8/2

≤64

/2≤

16/2

For P

. aer

ugin

osa

For A

cine

toba

cter

spp.

CEP

HEM

S (P

AR

ENTE

RA

L) (

Incl

udin

g ce

phal

ospo

rins

I, II,

III,

and

IV. P

leas

e re

fer

to G

loss

ary

I.)A

Cef

tazi

dim

e30

µg

≤14

≤17

15-1

718

-20

≥18

≥21

≥32 -

≤8

-Fo

r B. c

epac

iaB

Cef

epim

e30

µg

≤14

15-1

7≥

18≥

32≤

8B

C

efop

eraz

one

75 µ

g≤

15

16-2

0≥

21≥

64≤

16C C

Cef

otax

ime

orce

ftria

xone

30

µg

30 µ

g≤

14≤

1315

-22

14-2

0≥

23≥

21≥

64≥

64≤

8≤

8U

Cef

tizox

ime

30 µ

g≤

1415

-19

≥20

≥32

≤8

OM

oxal

acta

m

30 µ

g≤

1415

-22

≥23

≥64

≤8

CA

RB

APE

NEM

SB

Imip

enem

10 µ

g≤

1314

-15

≥16

≥16

≤4

BM

erop

enem

10 µ

g≤

13≤

15

14-1

516

-19

≥16

≥20

≥16 -

≤4

-Fo

r B. c

epac

iaM

ON

OB

AC

TAM

SB

Azt

reon

am30

µg

≤15

16-2

1≥

22≥

32≤

8A

MIN

OG

LYC

OSI

DES

AG

enta

mic

in10

µg

≤12

13-1

4≥

15≥

8≤

4B

Am

ikac

in30

µg

≤14

15-1

6≥

17≥

32≤

16B

Tobr

amyc

in10

µg

≤12

13-1

4≥

15≥

8≤

4C

Net

ilmic

in30

µg

≤12

13-1

4≥

15≥

32≤

12TE

TRA

CYC

LIN

ESU

Tetra

cycl

ine

30 µ

g≤

1415

-18

≥19

≥16

≤4

(7)

Org

anis

ms

that

are

sus

cept

ible

to

tetra

cycl

ine

are

also

con

side

red

susc

eptib

le to

dox

ycyc

line

and

min

ocyc

line.

H

owev

er,

som

e or

gani

sms

that

are

inte

rmed

iate

or

resi

stan

t to

tet

racy

clin

e m

ay b

esu

scep

tible

to d

oxyc

yclin

e or

min

ocyc

line

or b

oth.

OD

oxyc

yclin

e30

µg

≤12

13-1

5≥

16≥

16≤

4 O

Min

ocyc

line

30 µ

g≤

1415

-18

≥19

≥16

≤4

42

Tabl

e 2B

Non

-Ent

erob

acte

riace

aeM

2-D

isk

Diff

usio

n



Tabl

e 2B

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

ts

R

I S

R

S FL

UO

RO

QU

INO

LON

ESB B

Cip

roflo

xaci

nLe

voflo

xaci

n5

µg5

µg≤

15≤

1316

-20

14-1

6≥

21≥

17≥

4≥

8≤

1≤

2U U U

Lom

eflo

xaci

n or

norfl

oxac

in o

rof

loxa

cin

10 µ

g10

µg

5 µg

≤18

≤12

≤12

19-2

113

-16

13-1

5

≥22

≥17

≥16

≥8

≥16

≥8

≤2

≤4

≤2

O

Gat

iflox

acin

5 µg

≤

1415

-17

≥18

≥8

≤2

(8)

This

bre

akpo

int

appl

ies

to i

sola

tes

from

the

urin

ary

tract

onl

y.

PHEN

ICO

LS

CC

hlor

amph

enic

ol30

µg

≤12

13-1

7≥

18≥

32≤

8(9

) N

ot

rout

inel

y re

porte

d on

is

olat

es

from

th

eur

inar

y tra

ct.

FOLA

TE P

ATH

WAY

INH

IBIT

OR

SC

Trim

etho

prim

-sul

fam

etho

xazo

le1.

25/2

3.75

µg

≤10

11-1

5≥

16≥

8/15

2≤

2/38

US

ulfo

nam

ides

250

µg o

r30

0 µg

≤12

13-1

6≥

17≥

350

≤10

0(1

0)

The

sulfi

soxa

zole

di

sk

can

be

used

to

repr

esen

t an

y of

th

e cu

rren

tly

avai

labl

esu

lfona

mid

e pr

epar

atio

ns.


44

Tabl

e 2C

Stap

hylo

cocc

ussp

p.M

2-D

isk

Diff

usio

n


Tabl

e 2C

. Zo

ne D

iam

eter

Inte

rpre

tive

Stan

dard

s an

d Eq

uiva

lent

Min

imal

Inhi

bito

ry C

once

ntra

tion

(MIC

) Bre

akpo

ints

for S

taph

yloc

occu

ssp

p.

Test

ing

Con

ditio

ns

Med

ium

:M

uelle

r-H

into

n ag

arIn

ocul

um:

Dire

ct c

olon

y su

spen

sion

, equ

ival

ent t

o a

0.5

McF

arla

nd s

tand

ard

Incu

batio

n:33

to35

°C

(do

not e

xcee

d 35

°C

); am

bien

t air;

16

to 1

8 ho

urs;

24

hour

s fo

r oxa

cilli

n, m

ethi

cilli

n,na

fcill

in, a

nd v

anco

myc

in

Min

imal

QC

Rec

omm

enda

tions

(See

Tab

le 3

for a

ccep

tabl

e Q

C ra

nges

.)

Stap

hylo

cocc

us a

ureu

sAT

CC

®25

923

Esch

eric

hia

coli

ATC

C®

352

18 (f

or β

-lact

am/β

-lact

amas

e in

hibi

tor

com

bina

tions

)

Stap

hylo

cocc

us a

ureu

sAT

CC

® B

AA

-977

and

Sta

phyl

ococ

cus

aure

usAT

CC

® B

AA

-976

(for

qua

lity

asse

ssm

ent o

f the

clin

dam

ycin

indu

ctio

n te

st)

Gen

eral

Com

men

ts(1

)H

isto

rical

ly, r

esis

tanc

e to

the

pen

icill

inas

e-st

able

pen

icill

ins

(see

Glo

ssar

y I)

has

bee

n re

ferr

ed t

o as

“m

ethi

cilli

n re

sist

ance

,” th

us t

he a

cron

yms

MR

SA

(for

“met

hici

llin-

resi

stan

tS. a

ureu

s”) o

r MR

S (f

or “m

ethi

cilli

n-re

sist

ant s

taph

yloc

occi

”) a

re s

till c

omm

only

use

d ev

en th

ough

met

hici

llin

is n

o lo

nger

the

agen

t of c

hoic

efo

r te

stin

g or

trea

tmen

t. In

this

doc

umen

t, re

sist

ance

to th

ese

agen

ts m

ay b

e re

ferr

ed to

usi

ng s

ever

al te

rms

(e.g

., “M

RS

,” “m

ethi

cilli

n re

sist

ance

,” or

“ox

acill

inre

sist

ance

”).

(2)

For o

xaci

llin-

susc

eptib

le S

taph

yloc

occu

s au

reus

and

coag

ulas

e-ne

gativ

e st

aphy

loco

cci,

resu

lts fo

r par

ente

ral a

nd o

ral c

ephe

ms,

ββ-la

ctam

/ββ-la

ctam

ase

inhi

bito

r co

mbi

natio

ns, a

nd c

arba

pene

ms,

if t

este

d, s

houl

d be

rep

orte

d ac

cord

ing

to t

he r

esul

ts g

ener

ated

usi

ng r

outin

e in

terp

retiv

e cr

iteria

. See

com

men

t (3)

for

repo

rtin

g ββ -

lact

am r

esul

ts o

n ox

acill

in-r

esis

tant

str

ains

.

(3)

WA

RN

ING

:Fo

r ox

acill

in-r

esis

tant

Sta

phyl

ococ

cus

aure

usan

d co

agul

ase-

nega

tive

stap

hylo

cocc

i (M

RS

), ot

her

ββ -la

ctam

age

nts,

i.e.

, pen

icill

ins,

ββ-la

ctam

/ββ-

lact

amas

e in

hibi

tor

com

bina

tions

,cep

hem

s, a

nd c

arba

pene

ms,

may

app

ear a

ctiv

e in

vitr

obu

t are

not

effe

ctiv

e cl

inic

ally.

Res

ults

for t

hese

dru

gs s

houl

d be

repo

rted

as r

esis

tant

or

shou

ld n

ot b

e re

porte

d. T

his

is b

ecau

se m

ost

case

s of

doc

umen

ted

MR

S in

fect

ions

hav

e re

spon

ded

poor

ly t

o β-

lact

am t

hera

py,

orbe

caus

e co

nvin

cing

clin

ical

dat

a ha

ve y

et to

be

pres

ente

d th

at d

ocum

ent c

linic

al e

ffica

cy fo

r tho

se a

gent

s.

(4)

Det

ectio

n of

oxa

cilli

n re

sist

ance

: Tes

ts fo

r m

ecA

or fo

r th

e pr

otei

n ex

pres

sed

by m

ecA

, the

pen

icill

in-b

indi

ng p

rote

in 2

a (P

BP

2a, a

lso

calle

d PB

P2')

are

the

mos

t acc

urat

e m

etho

ds fo

r pre

dict

ion

of re

sist

ance

to o

xaci

llin

and

can

be u

sed

to c

onfir

m d

isk

test

resu

lts fo

r iso

late

s of

sta

phyl

ococ

ci fr

omse

rious

infe

ctio

ns. I

sola

tes

of s

taph

yloc

occi

tha

t ca

rry

the

mec

Age

ne, o

r th

at p

rodu

ce P

BP

2a (

the

mec

Age

ne p

rodu

ct),

shou

ld b

e re

port

ed a

sox

acill

in r

esis

tant

. Is

olat

es t

hat

do n

ot c

arry

mec

Aor

do

not

prod

uce

PBP

2a s

houl

d be

rep

orte

d as

oxa

cilli

n su

scep

tible

. B

ecau

se o

f th

e ra

reoc

curr

ence

of r

esis

tanc

e m

echa

nism

s ot

her t

han

mec

A, i

f MIC

test

s ar

e pe

rfor

med

in a

dditi

on to

dis

k di

ffusi

on, i

sola

tes

for w

hich

oxa

cilli

n M

ICs

are

≥≥4

µg/m

Lan

d ar

e m

ecA

nega

tive

or P

BP

2a n

egat

ive

shou

ld b

e re

port

ed a

s ox

acill

in r

esis

tant

.

(5)

Rou

tine

test

ing

of u

rine

isol

ates

of

S. s

apro

phyt

icus

is n

ot a

dvis

ed,

beca

use

infe

ctio

ns r

espo

nd t

o co

ncen

tratio

ns a

chie

ved

in u

rine

of a

ntim

icro

bial

age

nts

com

mon

ly u

sed

to tr

eat a

cute

, unc

ompl

icat

ed u

rinar

y tra

ct in

fect

ions

(e.g

., ni

trofu

rant

oin,

trim

etho

prim

± s

ulfa

met

hoxa

zole

, or a

fluo

roqu

inol

one)

.

(6)

For

som

e or

gani

sm/a

ntim

icro

bial

age

nt c

ombi

natio

ns, t

he a

bsen

ce o

f res

ista

nt s

train

s pr

eclu

des

defin

ing

any

resu

lts c

ateg

orie

s ot

her

than

“su

scep

tible

.” Fo

rst

rain

s yi

eldi

ng r

esul

ts s

ugge

stiv

e of

a “

nons

usce

ptib

le”

cate

gory

, or

gani

sm i

dent

ifica

tion

and

antim

icro

bial

sus

cept

ibili

ty t

est

resu

lts s

houl

d be

con

firm

ed.

Sub

sequ

ently

, the

isol

ates

sho

uld

be s

aved

and

sub

mitt

ed to

a re

fere

nce

labo

rato

ry th

at w

ill c

onfir

m re

sults

usi

ng a

CLS

I/NC

CLS

refe

renc

e di

lutio

n m

etho

d.

NO

TE:

Info

rmat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.


45

Tabl

e 2C

Stap

hylo

cocc

ussp

p.M

2-D

isk

Diff

usio

n


Tabl

e 2C

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

tsR

I

S R

S

PEN

ICIL

LIN

S(7

) P

enic

illin

-sus

cept

ible

st

aphy

loco

cci

are

also

susc

eptib

le

to

othe

r pe

nici

llins

, β-

lact

am/β

-lact

amas

ein

hibi

tor

com

bina

tions

, ce

phem

s,

and

carb

apen

ems

appr

oved

fo

r us

e by

th

e FD

Afo

r st

aphy

loco

ccal

infe

ctio

ns.

Pen

icill

in-r

esis

tant

, ox

acill

in-s

usce

ptib

lest

rain

s ar

e re

sist

ant

to p

enic

illin

ase-

labi

le p

enic

illin

s bu

tsu

scep

tible

to

othe

r pe

nici

llina

se-s

tabl

e pe

nici

llins

, β-

lact

am/β

-lact

amas

e in

hibi

tor

com

bina

tions

, re

leva

ntce

phem

s,

and

carb

apen

ems.

O

xaci

llin-

resi

stan

tst

aphy

loco

cci

are

resi

stan

t to

all

curr

ently

ava

ilabl

e β-

lact

am a

ntib

iotic

s. T

hus,

sus

cept

ibili

ty o

r re

sist

ance

to a

wid

e ar

ray

of β

-lact

am a

ntib

iotic

s m

ay b

e de

duce

d fro

mte

stin

g on

ly p

enic

illin

and

oxa

cilli

n. R

outin

e te

stin

g of

othe

r pe

nici

llins

, β-

lact

am/β

-lact

amas

e in

hibi

tor

com

bina

tions

, ce

phem

s,

and

carb

apen

ems

is

not

advi

sed.

See

com

men

t (3)

. A

Pen

icill

in10

uni

ts≤

28-

≥29

β-la

ctam

ase

≤0.

12(8

) P

enic

illin

-res

ista

nt,

oxac

illin

-sus

cept

ible

stra

ins

ofSt

aphy

loco

ccus

aur

eus

prod

uce

β-la

ctam

ase,

and

the

test

ing

of

the

10-u

nit

peni

cilli

n di

sk

inst

ead

of

the

ampi

cilli

n di

sk is

pre

ferr

ed.

Pen

icill

in s

houl

d be

use

d to

test

the

susc

eptib

ility

of a

ll β-

lact

amas

e-la

bile

pen

icill

ins,

such

as

am

pici

llin,

am

oxic

illin

, az

loci

llin,

ca

rben

icill

in,

mez

loci

llin,

pip

erac

illin

, and

tica

rcill

in. L

ikew

ise,

a p

ositi

veβ-

lact

amas

e te

st

(see

M

2-A

8,

Sec

tion

8)

pred

icts

resi

stan

ce

to

thes

e ag

ents

. Fo

r ox

acill

in-r

esis

tant

stap

hylo

cocc

i, re

port

as re

sist

ant o

r do

not r

epor

t.


46

Tabl

e 2C

Stap

hylo

cocc

ussp

p.M

2-D

isk

Diff

usio

n


Tabl

e 2C

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

IC B

reak

poin

ts(µµ

g/m

L)

Com

men

ts

R

I S

R

S PE

NIC

ILLI

NS

(Con

tinue

d)A

Oxa

cilli

n30

µµg

cefo

xitin

1 µg

oxa

cilli

n

30 µµ

g ce

foxi

tin

1 µg

oxa

cilli

n

≤≤19

≤10

≤≤24

≤17

-

11-1

2 - -

≥≥20

≥13

≥≥25

≥18

≥≥4

(oxa

cilli

n)

≥4

≥0.

5 (o

xaci

llin)

≥0.

5

≤2

≤2

≤0.

25

≤0.

25

For

S. a

ureu

san

d S.

lugd

unen

sis

For S

. aur

eus

and

S. lu

gdun

ensi

s

(9)

For

S. a

ureu

san

d S.

lugd

unen

sis,

the

cefo

xitin

dis

k te

stis

com

para

ble

to th

e ox

acill

in d

isk

test

for p

redi

ctio

n of

mec

A-

med

iate

d re

sist

ance

to

oxac

illin

; ho

wev

er, t

he c

efox

itin

disk

test

is e

asie

r to

rea

d an

d th

us is

the

pref

erre

d m

etho

d.

(10)

If in

term

edia

te re

sults

are

obt

aine

d fo

r S. a

ureu

s,pe

rfor

mte

stin

g fo

r mec

Aor

PB

P2a

, the

cef

oxiti

n di

sk te

st, a

n ox

acill

inM

IC te

st, o

r th

e ox

acill

in-s

alt a

gar

scre

enin

g te

st. R

epor

t the

resu

lt of

the

alte

rnat

ive

test

rat

her

than

the

int

erm

edia

tere

sult.

For

coag

ulas

e-ne

gativ

e st

aphy

loco

cci e

xcep

tS. l

ugdu

nens

is

For c

oagu

lase

-neg

ativ

e st

aphy

loco

cci e

xcep

tS. l

ugdu

nens

is

(11)

The

cef

oxiti

n di

sk te

st is

the

pref

erre

d m

etho

d fo

r tes

ting

coag

ulas

e-ne

gativ

e st

aphy

loco

cci.

Alth

ough

ox

acill

inin

terp

retiv

e cr

iteria

fo

r co

agul

ase-

nega

tive

stap

hylo

cocc

ico

rrel

ate

with

the

pres

ence

or

abse

nce

of th

e ge

ne e

ncod

ing

met

hici

llin/

oxac

illin

re

sist

ance

(m

ecA

) in

S.

epi

derm

idis

,th

ese

inte

rpre

tive

crite

ria m

ay o

verc

all

resi

stan

ce f

or o

ther

coag

ulas

e-ne

gativ

e st

aphy

loco

cci,

e.g.

, S.

sap

roph

ytic

us.

The

cefo

xitin

dis

k te

st h

as h

ighe

r sp

ecifi

city

and

equ

alse

nsiti

vity

to

the

oxac

illin

dis

k te

st f

or c

oagu

lase

-neg

ativ

est

aphy

loco

cci.

(12)

If

a pe

nici

llina

se-s

tabl

e pe

nici

llin

is t

este

d, o

xaci

llin

isth

e pr

efer

red

agen

t an

d re

sults

can

be

appl

ied

to t

he o

ther

peni

cilli

nase

-sta

ble

peni

cilli

ns,

clox

acill

in,

dicl

oxac

illin

, an

dflu

clox

acill

in.

Oxa

cilli

n is

mor

e re

sist

ant

to d

egra

datio

n in

stor

age

and

is

mor

e lik

ely

to

dete

ct

hete

rore

sist

ant

stap

hylo

cocc

al s

trai

ns. C

loxa

cilli

n di

sks

shou

ld n

ot b

e us

ed,

beca

use

they

may

not

det

ect

oxac

illin

-res

ista

nt S

. au

reus

.C

efox

itin

may

be

test

ed in

stea

d of

oxa

cilli

n. S

ee c

omm

ents

(9),

(10)

, (11

), an

d (1

3).

(13)

Fo

r al

l st

aphy

loco

cci,

read

the

oxa

cilli

n di

sk f

or l

ight

grow

th w

ithin

the

zon

e of

inh

ibiti

on u

sing

tra

nsm

itted

lig

ht(p

late

hel

d up

to

light

); an

y di

scer

nabl

e gr

owth

with

in t

hezo

ne o

f in

hibi

tion

is in

dica

tive

of o

xaci

llin

resi

stan

ce.

Rea

dth

e ce

foxi

tin d

isk

usin

g re

flect

ed li

ght.


47

Tabl

e 2C

Stap

hylo

cocc

ussp

p.M

2-D

isk

Diff

usio

n


Tabl

e 2C

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

tsR

I

S R

S

PEN

ICIL

LIN

S (C

ontin

ued)

OA

mpi

cilli

n10

µg

≤28

- ≥

29β-

lact

amas

e≤

0.25

(14)

Cla

ss re

pres

enta

tive

for a

mpi

cilli

n an

d am

oxic

illin

. (1

5) F

or o

xaci

llin-

resi

stan

t sta

phyl

ococ

ci, r

epor

t as

resi

stan

t or

do n

ot re

port.

OM

ethi

cilli

n5

µg

≤9

10-1

3≥

14≥

16≤

8(1

6) D

isk

diffu

sion

bre

akpo

ints

are

for u

se w

ith S

. aur

eus

only.

See

com

men

t (12

).O

Naf

cilli

n 1

µg≤

1011

-12

≥13

- ≤

1(1

7) D

isk

diffu

sion

bre

akpo

ints

are

for u

se w

ith S

. aur

eus

only.

See

com

men

t (12

).ββ -

LAC

TAM

/ββ-L

AC

TAM

ASE

INH

IBIT

OR

CO

MB

INAT

ION

SS

ee c

omm

ents

(3) a

nd (7

).(1

8) F

or o

xaci

llin-

resi

stan

t sta

phyl

ococ

ci, r

epor

t as

resi

stan

t or

do n

ot re

port.

OA

mox

icill

in-c

lavu

lani

c ac

id

20/1

0 µg

≤19

- ≥

20≥

8/4

≤4/

2O

Am

pici

llin-

sulb

acta

m10

/10

µg≤

1112

-14

≥15

≥32

/16

≤8/

4O

Pip

erac

illin

-tazo

bact

am10

0/10

µg

≤17

- ≥

18≥

16/4

≤8/

4O

Tica

rcill

in-c

lavu

lani

c ac

id75

/10

µg≤

22-

≥23

≥16

/2≤

8/2

CEP

HEM

S (P

AR

ENTE

RA

L) (

Incl

udin

g ce

phal

ospo

rins

I, II,

III,

and

IV. P

leas

e re

fer

to G

loss

ary

I.)S

ee c

omm

ent (

7).

(19)

For

oxa

cilli

n-re

sist

ant s

taph

yloc

occi

, rep

ort a

s re

sist

ant o

rdo

not

repo

rt.O

Cef

aman

dole

30 µ

g≤

1415

-17

≥18

≥32

≤8

OC

efaz

olin

30

µg

≤14

15-1

7≥

18≥

32≤

8O

Cef

epim

e 30

µg

≤14

15-1

7≥

18≥

32≤

8O

Cef

met

azol

e30

µg

≤12

13-1

5≥

16≥

64≤

16O

Cef

onic

id30

µg

≤14

15-1

7≥

18≥

32≤

8O

Cef

oper

azon

e75

µg

≤15

16-2

0≥

21≥

64≤

16O

Cef

otax

ime

30 µ

g ≤

1415

-22

≥23

≥64

≤8

OC

efot

etan

30 µ

g≤

1213

-15

≥16

≥64

≤16

OC

efta

zidi

me

30 µ

g≤

1415

-17

≥18

≥32

≤8

OC

eftiz

oxim

e30

µg

≤14

15-1

9≥

20≥

32≤

8O

Cef

triax

one

30 µ

g≤

1314

-20

≥21

≥64

≤8

OC

efur

oxim

e so

dium

(par

ente

ral)

30 µ

g≤

1415

-17

≥18

≥32

≤

8O

Cep

halo

thin

30 µ

g≤

1415

-17

≥18

≥32

≤8

OM

oxal

acta

m

30 µ

g≤

1415

-22

≥23

≥64

≤

8C

EPH

EMS

(OR

AL)

S

ee c

omm

ent (

7).

(20)

For

oxa

cilli

n-re

sist

ant s

taph

yloc

occi

, rep

ort a

s re

sist

ant o

r do

not

repo

rt.O

Cef

aclo

r 30

µg

≤14

15

-17

≥18

≥

32≤

8O

Cef

dini

r 5

µg≤

1617

-19

≥20

≥4

≤1

OC

efpo

doxi

me

10 µ

g≤

17

18-2

0 ≥

21

≥8

≤2

O

Cef

proz

il 30

µg

≤14

15-1

7 ≥

18≥

32≤

8O

Cef

urox

ime

axet

il (o

ral)

30 µ

g≤

1415

-22

≥23

≥32

≤

4O

Lora

carb

ef

30 µ

g≤

1415

-17

≥18

≥32

≤8


48

Tabl

e 2C

Stap

hylo

cocc

ussp

p.M

2-D

isk

Diff

usio

n

Tabl

e 2C

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

tsR

I

S R

S

CA

RB

APE

NEM

SS

ee c

omm

ent (

7)(2

1) F

or o

xaci

llin-

resi

stan

t sta

phyl

ococ

ci, r

epor

t as

resi

stan

t or

do n

ot re

port.

O

Erta

pene

m

10 µ

g ≤

1516

-18

≥19

≥8

≤2

OIm

ipen

em

10 µ

g≤

1314

-15

≥16

≥16

≤4

OM

erop

enem

10

µg

≤13

14-1

5 ≥

16≥

16≤

4G

LYC

OPE

PTID

ESB

Va

ncom

ycin

30 µ

g-

- ≥

15-

≤4

(22)

A

ll st

aphy

loco

ccal

iso

late

s fo

r w

hich

van

com

ycin

zon

edi

amet

ers

are

14 m

m o

r les

s sh

ould

be

test

ed b

y a

refe

renc

e M

ICm

etho

d.

The

disk

di

ffusi

on

proc

edur

e w

ill

not

diffe

rent

iate

stra

ins

with

red

uced

sus

cept

ibili

ty t

o va

ncom

ycin

(M

ICs

4-8

µµ g/m

L) f

rom

sus

cept

ible

str

ains

(M

IC r

ange

0.5

-2 µµ

g/m

L) e

ven

whe

n in

cuba

ted

for 2

4 ho

urs.

Add

ition

ally

, van

com

ycin

-res

ista

ntS.

aur

eus

(VR

SA)

stra

ins

(MIC

s ≥≥ 3

2 µµ g

/mL)

may

pro

duce

onl

ysu

btle

gro

wth

aro

und

a va

ncom

ycin

dis

k. A

BH

I van

com

ycin

aga

rsc

reen

pla

te c

onta

inin

g 6

µµ g/m

Lof

van

com

ycin

, su

ch a

s th

atus

ed fo

r det

ectio

n of

van

com

ycin

-res

ista

nt e

nter

ococ

ci (s

ee M

7,Ta

ble

2D),

may

be

inoc

ulat

ed t

o en

hanc

e th

e se

nsiti

vity

of

dete

ctin

g va

ncom

ycin

-inte

rmed

iate

an

d va

ncom

ycin

-res

ista

ntst

rain

s of

S. a

ureu

s. S

end

any

stap

hylo

cocc

i det

erm

ined

to h

ave

anel

evat

ed M

IC to

van

com

ycin

(≥4

µg/m

L) to

a re

fere

nce

labo

rato

ry.

Inv.

Teic

opla

nin

30 µ

g≤

1011

-13

≥14

≥32

≤

8LI

POPE

PTID

ESB

Dap

tom

ycin

30 µµ

g-

-≥≥

16-

≤≤1

See

com

men

t (6)

.

AM

INO

GLY

CO

SID

ESC

Gen

tam

icin

10 µ

g≤

1213

-14

≥15

≥8

≤4

OA

mik

acin

30 µ

g≤

1415

-16

≥17

≥32

≤16

OK

anam

ycin

30 µ

g≤

1314

-17

≥18

≥25

≤6

ON

etilm

icin

30 µ

g≤

1213

-14

≥15

≥32

≤12

OTo

bram

ycin

10 µ

g≤

1213

-14

≥15

≥8

≤4

MA

CR

OLI

DES

B B B

Azi

thro

myc

in o

rcl

arith

rom

ycin

or

eryt

hrom

ycin

15 µ

g15

µg

15 µ

g

≤13

≤13

≤13

14-1

714

-17

14-2

2

≥18

≥18

≥23

≥8

≥8

≥8

≤2

≤2

≤0.

5

(23)

Not

rout

inel

y re

porte

d on

isol

ates

from

the

urin

ary

tract

.

O

Diri

thro

myc

in15

µg

≤15

16-1

8≥

19≥

8≤

2K

ETO

LID

ESB

Telit

hrom

ycin

15 µ

g≤

1819

-21

≥22

≥4

≤1



49

Tabl

e 2C

Stap

hylo

cocc

ussp

p.M

2-D

isk

Diff

usio

n


Tabl

e 2C

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

ts

R

I S

R

S TE

TRA

CYC

LIN

ES

C

Tetra

cycl

ine

30 µ

g≤

1415

-18

≥19

≥16

≤4

(24)

Org

anis

ms

that

are

sus

cept

ible

to

tetra

cycl

ine

are

also

cons

ider

ed s

usce

ptib

le to

dox

ycyc

line

and

min

ocyc

line.

How

ever

,so

me

orga

nism

s th

at a

re in

term

edia

te o

r re

sist

ant t

o te

tracy

clin

em

ay b

e su

scep

tible

to d

oxyc

yclin

e or

min

ocyc

line

or b

oth.

O

Dox

ycyc

line

30 µ

g ≤

1213

-15

≥16

≥16

≤4

O

Min

ocyc

line

30 µ

g≤

1415

-18

≥19

≥16

≤4

FLU

OR

OQ

UIN

OLO

NES

(25)

St

aphy

loco

ccus

spp.

m

ay

deve

lop

resi

stan

ce

durin

gpr

olon

ged

ther

apy

with

qui

nolo

nes.

The

refo

re,

isol

ates

tha

t ar

ein

itial

ly s

usce

ptib

le m

ay b

ecom

e re

sist

ant w

ithin

thre

e to

four

day

saf

ter

initi

atio

n of

the

rapy

. Te

stin

g of

rep

eat

isol

ates

may

be

war

rant

ed.

C C C C C

Cip

roflo

xaci

n or

le

voflo

xaci

n or

oflo

xaci

nG

atifl

oxac

in o

rm

oxifl

oxac

in

5 µg

5 µg

5 µg

5 µg

5

µµ g

≤15

≤≤15

≤≤14

≤≤19

≤≤20

16-2

016

-18

15-1

720

-22

21-2

3

≥21

≥≥19

≥≥18

≥≥23

≥≥24

≥4

≥4

≥4

≥≥2

≥≥2

≤1

≤1

≤1

≤≤0.

5 ≤≤

0.5

U U

Lom

eflo

xaci

n or

norfl

oxac

in

10 µ

g10

µg

≤18

≤12

19-2

113

-16

≥22

≥17

≥8

≥16

≤

2≤

4

O

Eno

xaci

n 10

µg

≤14

15-1

7≥

18

≥8

≤2

(26)

FD

A-a

ppro

ved

for S

. sap

roph

ytic

usan

d S.

epi

derm

idis

(not

S. a

ureu

s)O

G

repa

floxa

cin

5 µg

≤

1415

-17

≥18

≥4

≤1

OSp

arflo

xaci

n 5

µg

≤15

16-1

8 ≥

19≥

2 ≤

0.5

Inv.

Fler

oxac

in5

µg

≤15

16-1

8≥

19

≥8

≤2

NIT

RO

FUR

AN

TOIN

S U

Nitr

ofur

anto

in30

0 µg

≤14

15

-16

≥17

≥12

8≤

32



Tabl

e 2C

Stap

hylo

cocc

ussp

p.M

2-D

isk

Diff

usio

n

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

ts

R

I S

R

S LI

NC

OSA

MID

ES

B

Clin

dam

ycin

2 µg

≤

14

15-2

0 ≥

21

≥4

≤0.

5(2

7) M

acro

lide-

resi

stan

t is

olat

es o

f S.

aur

eus

and

coag

ulas

e-ne

gativ

e St

aphy

loco

ccus

spp.

may

hav

e co

nstit

utiv

e or

indu

cibl

ere

sist

ance

to c

linda

myc

in [m

ethy

latio

n of

the

23S

rR

NA

enco

ded

by

the

erm

gene

al

so

refe

rred

to

as

M

LSB

(mac

rolid

e,lin

coso

mid

e, a

nd t

ype

B s

trept

ogra

min

) re

sist

ance

] or

may

be

resi

stan

t on

ly t

o m

acro

lides

(ef

flux-

mec

hani

sm e

ncod

ed b

y th

em

srA

gene

). I

nduc

ible

clin

dam

ycin

res

ista

nce

can

be d

etec

ted

usin

g a

disk

app

roxi

mat

ion

test

by

plac

ing

a 2-

µg c

linda

myc

indi

sk f

rom

15

mm

to

26 m

m a

way

fro

m t

he e

dge

of a

15-

µger

ythr

omyc

in d

isk

as p

art o

f the

nor

mal

dis

k di

ffusi

on p

roce

dure

.Fo

llow

ing

incu

batio

n, o

rgan

ism

s th

at d

o no

t sho

w fl

atte

ning

of t

hecl

inda

myc

in z

one

shou

ld b

e re

porte

d as

clin

dam

ycin

sus

cept

ible

.O

rgan

ism

s th

at s

how

flat

teni

ng o

f the

clin

dam

ycin

zon

e ad

jace

ntto

the

ery

thro

myc

in d

isk

(ref

erre

d to

as

a “D

” zo

ne)

indi

cate

indu

cibl

e cl

inda

myc

in

resi

stan

ce.

Suc

h is

olat

es

shou

ld

bere

porte

d as

“cl

inda

myc

in r

esis

tant

.” A

com

men

t tha

t “Th

is is

olat

eis

pre

sum

ed t

o be

res

ista

nt b

ased

on

dete

ctio

n of

ind

ucib

lecl

inda

myc

in re

sist

ance

. Clin

dam

ycin

may

stil

l be

effe

ctiv

e in

som

epa

tient

s.”

may

be

in

clud

ed.

For

qual

ity

cont

rol/q

ualit

yas

sess

men

t rec

omm

enda

tions

, ref

er to

Tab

le 3

.S

ee c

omm

ent (

23).

FOLA

TE P

ATH

WAY

INH

IBIT

OR

SB

Trim

etho

prim

-sul

fam

etho

xazo

le

1.25

/23.

75 µ

g≤

10

11-1

5 ≥

16

≥8/

152

≤2/

38

U

Sul

fona

mid

es

250

or 3

00 µ

g ≤

12

13-1

6 ≥

17

≥35

0≤

100

(28)

The

sul

fisox

azol

e di

sk c

an b

e us

ed to

rep

rese

nt a

ny o

f the

curr

ently

ava

ilabl

e su

lfona

mid

e pr

epar

atio

ns.

U

Trim

etho

prim

5

µg

≤10

11

-15

≥16

≥16

≤

4 PH

ENIC

OLS

CC

hlor

amph

enic

ol30

µg

≤12

13

-17

≥18

≥32

≤8

See

com

men

t (23

).

AN

SAM

YCIN

SC

R

ifam

pin

5 µg

≤16

17-1

9≥

20≥

4≤

1(2

9)R

x:R

ifam

pin

shou

ld n

ot b

e us

ed a

lone

for c

hem

othe

rapy

.ST

REP

TOG

RA

MIN

S

CQ

uinu

pris

tin-d

alfo

pris

tin15

µg

≤15

16

-18

≥19

≥

4≤

1O

XAZO

LID

INO

NES

BLi

nezo

lid30

µg

- -

≥21

- ≤

4S

ee c

omm

ent (

6).

Tabl

e 2C

. (C

ontin

ued)



Table 2C. (Continued)

Disk Diffusion Testa for Prediction of mecA-mediated Resistance in Staphylococci

Antimicrobial Agent

(Disk Content)

Organism Group Zone Diameter,Nearest Whole mm

Comments

Cefoxitin (30 µg) S. aureus and S.lugdunensis

≤ 19 ≥ 20 (30) S. aureus for which cefoxitindisk diffusion zones are ≤ 19 mmshould be reported as oxacillinresistant. Those for whichcefoxitin zones are ≥ 20 mmshould be reported as oxacillinsusceptible.

Coagulase-negativestaphylococci exceptS. lugdunensis

≤ 24 ≥ 25 (31) Coagulase-negativestaphylococci for which cefoxitindisk diffusion zones are ≤ 24 mmshould be reported as oxacillinresistant. Those for whichcefoxitin zones are ≥ 25 mmshould be reported as oxacillinsusceptible.

a Use standard disk diffusion testing conditions and incubate for 24 hours; however, results may be reported after 18hours incubation if resistant. Read the cefoxitin disk test using reflected light.

Tabl

e 2C

Stap

hylo

cocc

ussp

p.M

2-D

isk

Diff

usio

n


Tabl

e 2D

Ente

roco

ccus

spp.

M2-

Dis

k D

iffus

ion

52 ©Clinical and Laboratory Standards Institute. All rights reserved.

Tabl

e 2D

. Zo

ne D

iam

eter

Inte

rpre

tive

Stan

dard

s an

d Eq

uiva

lent

Min

imal

Inhi

bito

ry C

once

ntra

tion

(MIC

) Bre

akpo

ints

forE

nter

ococ

cus

spp.

Test

ing

Con

ditio

ns

Med

ium

:M

uelle

r-H

into

n ag

arIn

ocul

um:

Gro

wth

m

etho

d or

di

rect

co

lony

su

spen

sion

,eq

uiva

lent

to a

0.5

McF

arla

nd s

tand

ard

Incu

batio

n:35

°C

±2

degr

ees;

am

bien

t air;

16

to 1

8 ho

urs;

24

hour

s fo

r van

com

ycin

Min

imal

QC

Rec

omm

enda

tions

(See

Tab

le 3

for a

ccep

tabl

e Q

C ra

nges

.)

Stap

hylo

cocc

us a

ureu

s AT

CC

® 2

5923

Gen

eral

Com

men

ts

(1)

WA

RN

ING

:Fo

r En

tero

cocc

us

spp.

, ce

phal

ospo

rins,

am

inog

lyco

side

s (e

xcep

t fo

r hi

gh-le

vel

resi

stan

ce

scre

enin

g),

clin

dam

ycin

, an

d tri

met

hopr

im-

sulfa

met

hoxa

zole

may

app

ear a

ctiv

e in

vitr

obu

t are

not

effe

ctiv

e cl

inic

ally,

and

isol

ates

sho

uld

not b

e re

porte

d as

sus

cept

ible

.

(2)

Syn

ergy

bet

wee

n am

pici

llin,

pen

icill

in, o

r van

com

ycin

and

an

amin

ogly

cosi

de c

an b

e pr

edic

ted

for e

nter

ococ

ci b

y us

ing

a hi

gh-le

vel a

min

ogly

cosi

de (g

enta

mic

inan

d st

rept

omyc

in)

scre

enin

g te

st. O

ther

am

inog

lyco

side

s ne

ed n

ot b

e te

sted

, bec

ause

thei

r ac

tiviti

es a

gain

st e

nter

ococ

ci a

re n

ot s

uper

ior

to g

enta

mic

in a

ndst

rept

omyc

in.

(3)

Bec

ause

of l

imite

d al

tern

ativ

es, c

hlor

amph

enic

ol, e

ryth

rom

ycin

, tet

racy

clin

e (o

r dox

ycyc

line

or m

inoc

yclin

e), a

nd ri

fam

pin

may

be

used

for v

anco

myc

in-r

esis

tant

ente

roco

cci (

VR

E),

and

cons

ulta

tion

with

an

infe

ctio

us d

isea

se p

ract

ition

er is

reco

mm

ende

d.

(4)

For

som

e or

gani

sm/a

ntim

icro

bial

age

nt c

ombi

natio

ns,

the

abse

nce

of r

esis

tant

str

ains

pre

clud

es d

efin

ing

any

resu

lts c

ateg

orie

s ot

her

than

“sus

cept

ible

.” F

or s

trai

ns y

ield

ing

resu

lts s

ugge

stiv

e of

a “

nons

usce

ptib

le”

cate

gory

, org

anis

m id

entif

icat

ion

and

antim

icro

bial

sus

cept

ibili

ty te

stre

sults

sho

uld

be c

onfir

med

. Sub

sequ

ently

, the

isol

ates

sho

uld

be s

aved

and

sub

mitt

ed to

a r

efer

ence

labo

rato

ry th

at w

ill c

onfir

m r

esul

ts u

sing

aC

LSI/N

CC

LS r

efer

ence

dilu

tion

met

hod.

NO

TE:

Info

rmat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.



Tabl

e 2D

Ente

roco

ccus

spp.

M2-

Dis

k D

iffus

ion

Tabl

e 2D

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

tsR

I

S R

S

PEN

ICIL

LIN

SA A

Pen

icill

in o

r am

pici

llin

10 u

nits

10 µ

g≤

14≤

16

- - ≥

15≥

17≥

16≥

16

≤8

≤8

(5)

Am

pici

llin

is t

he c

lass

rep

rese

ntat

ive

for

ampi

cilli

n an

dam

oxic

illin

. A

mpi

cilli

n re

sults

m

ay

be

used

to

pr

edic

tsu

scep

tibili

ty

to

amox

icill

in-c

lavu

lani

c ac

id,

ampi

cilli

n-su

lbac

tam

, pi

pera

cilli

n,

and

pipe

raci

llin-

tazo

bact

am

amon

gno

n-β-

lact

amas

e-pr

oduc

ing

ente

roco

cci.

(6)

P

enic

illin

su

scep

tibili

ty

may

be

us

ed

to

pred

ict

the

susc

eptib

ility

to

am

pici

llin,

am

oxic

illin

, am

pici

llin-

sulb

acta

m,

amox

icill

in-c

lavu

lani

c ac

id,

pipe

raci

llin,

an

d pi

pera

cilli

n-ta

zoba

ctam

fo

r no

n-β-

lact

amas

e-pr

oduc

ing

ente

roco

cci.

Am

pici

llin

susc

eptib

ility

ca

n be

us

ed

to

pred

ict

imip

enem

susc

eptib

ility

, pr

ovid

ed

the

spec

ies

is

conf

irmed

to

be

E.

faec

alis

.

(7)

Rx:

The

“sus

cept

ible

” ca

tego

ry f

or p

enic

illin

or

ampi

cilli

nim

plie

s th

e ne

ed fo

r hig

h-do

se th

erap

y fo

r ser

ious

ent

eroc

occa

lin

fect

ions

. E

nter

ococ

cal

endo

card

itis

requ

ires

com

bine

dth

erap

y w

ith h

igh-

dose

pen

icill

in o

r hi

gh-d

ose

ampi

cilli

n, o

rva

ncom

ycin

or

teic

opla

nin

plus

gen

tam

icin

or

stre

ptom

ycin

for

bact

eric

idal

act

ion.

(8)

B

ecau

se

ampi

cilli

n or

pe

nici

llin

resi

stan

ce

amon

gen

tero

cocc

i du

e to

β-

lact

amas

e pr

oduc

tion

is

not

relia

bly

dete

cted

us

ing

rout

ine

disk

or

di

lutio

n m

etho

ds,

a di

rect

,ni

troce

fin-b

ased

β-la

ctam

ase

test

is

reco

mm

ende

d fo

r bl

ood

and

cere

bros

pina

l flu

id i

sola

tes.

Apo

sitiv

e β-

lact

amas

e te

stpr

edic

ts r

esis

tanc

e to

pen

icill

in,

as w

ell

as a

min

o-,

carb

oxy-

,an

d ur

eido

peni

cilli

ns.

GLY

CO

PEPT

IDES

B

Vanc

omyc

in

30 µ

g ≤

14

15-1

6≥

17

≥32

≤

4 (9

) W

hen

test

ing

vanc

omyc

in a

gain

st e

nter

ococ

ci,

plat

essh

ould

be

held

a fu

ll 24

hou

rs a

nd e

xam

ined

usi

ng tr

ansm

itted

light

; the

pre

senc

e of

a h

aze

or a

ny g

row

th w

ithin

the

zone

of

inhi

bitio

n in

dica

tes

resi

stan

ce.

Org

anis

ms

with

int

erm

edia

tezo

nes

shou

ld b

e te

sted

by

an M

IC m

etho

d as

des

crib

ed i

nC

LSI/N

CC

LS d

ocum

ent

M7.

See

als

o th

e va

ncom

ycin

aga

rsc

reen

test

des

crib

ed in

M7,

Tab

le 2

D.

See

com

men

ts (2

) and

(7).

Inv.

Teic

opla

nin

30 µ

g≤

1011

-13

≥14

≥32

≤8

See

com

men

ts (2

) and

(7).

LIPO

PEPT

IDES

BD

apto

myc

in30

µµg

--

≥≥11

-≤≤

4 Se

e co

mm

ent (

4).

MA

CR

OLI

DES

C

Ery

thro

myc

in15

µg

≤13

14

-22

≥23

≥8

≤0.

5(1

0) N

ot ro

utin

ely

repo

rted

on is

olat

es fr

om th

e ur

inar

y tra

ct.


Tabl

e 2D

Ente

roco

ccus

spp.

M2-

Dis

k D

iffus

ion


Tabl

e 2D

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

tsR

I

S R

S

TETR

AC

YCLI

NES

Se

e co

mm

ent (

3).

CTe

tracy

clin

e30

µg

≤14

15-1

8≥

19≥

16≤

4 (1

1)

Org

anis

ms

that

ar

e su

scep

tible

to

tetra

cycl

ine

are

also

con

side

red

susc

eptib

le t

odo

xycy

clin

e an

d m

inoc

yclin

e.

How

ever

, so

me

orga

nism

s th

at a

re in

term

edia

te o

r re

sist

ant

tote

tracy

clin

e m

ay b

e su

scep

tible

to

doxy

cycl

ine

or m

inoc

yclin

e or

bot

h.O

D

oxyc

yclin

e30

µg

≤12

13-1

5≥

16≥

16≤

4 O

M

inoc

yclin

e30

µg

≤14

15

-18

≥19

≥16

≤4

FLU

OR

OQ

UIN

OLO

NES

U U U

Cip

roflo

xaci

nLe

voflo

xaci

nN

orflo

xaci

n

5 µg

5 µg

10 µ

g

≤15

≤13

≤12

16-2

014

-16

13-1

6

≥21

≥17

≥17

≥4

≥

8≥

16

≤1

≤2

≤4

OG

atifl

oxac

in5

µg

≤14

15-1

7 ≥

18

≥8

≤2

(12)

Thi

s br

eakp

oint

app

lies

to u

rinar

y tra

ctis

olat

es o

nly.

NIT

RO

FUR

AN

TOIN

SU

N

itrof

uran

toin

30

0 µg

≤

14

15-1

6 ≥

17

≥12

8≤

32

AN

SAM

YCIN

SC

R

ifam

pin

5 µg

≤

16

17-1

9≥

20≥

4 ≤

1 (1

3)

Rx:

R

ifam

pin

shou

ld n

ot b

e us

ed a

lone

for c

hem

othe

rapy

.

See

com

men

t (3)

.

FOSF

OM

YCIN

SU

Fo

sfom

ycin

20

0 µg

≤

12

13-1

5≥

16

≥25

6≤

64(1

4)

For

use

with

E. fa

ecal

ison

ly. T

he 2

00-µ

gfo

sfom

ycin

dis

k co

ntai

ns 5

0 µg

of

gluc

ose-

6-ph

osph

ate.

PH

ENIC

OLS

CC

hlor

amph

enic

ol

30 µ

g≤

12

13-1

7 ≥

18

≥32

≤8

See

com

men

t (3)

.S

ee c

omm

ent (

10).

STR

EPTO

GR

AM

INS

B

Qui

nupr

istin

-dal

fopr

istin

15 µ

g≤

1516

-18

≥19

≥

4≤

1O

XAZO

LID

INO

NES

BLi

nezo

lid30

µg

≤20

21-2

2≥

23

≥8

≤2



Disk Diffusion Screening Tests for High-Level Aminoglycoside Resistance (HLAR)a

Test/ResultGroup

AntimicrobialAgent

DiskContent

Zone Diameter,Nearest Whole mm

Equivalent MICBreakpoints (µµg/mL) Comments

R I S R SC Gentamicin

(HLAR) 120 µg 6 7-9 ≥ 10 > 500 ≤ 500 (15) If the zone is 7 to 9 mm, the

test is inconclusive, and an agardilution or broth microdilutionscreen test should be performedto confirm resistance. Seecomments (2) and (7).

C Streptomycin(HLAR)

300 µg 6 7-9 ≥ 10 - - (16) MIC correlates forstreptomycin broth microdilutionare resistant >1000 µg/mL andfor agar dilution > 2000 µg/mL.See comments (2), (7), and (15).

Footnote

a. For QC of HLAR screen tests, use Enterococcus faecalis ATCC® 29212 (see Table 3, Footnote f [Disk Testing] foracceptable QC ranges).

See M7,Table 2D (MIC Testing) which summarizes additional screening tests for vancomycin, high-levelaminoglycoside resistance, and supplemental tests for identification that may be helpful for vancomycin-resistant enterococci.

Table 2D. (Continued)

Tabl

e 2D

Ente

roco

ccus

spp.

M2-

Dis

k D

iffus

ion


Tabl

e 2E

Hae

mop

hilu

sspp

.M

2-D

isk

Diff

usio

n


Tabl

e 2E

. Zo

ne D

iam

eter

Inte

rpre

tive

Stan

dard

s an

d Eq

uiva

lent

Min

imal

Inhi

bito

ry C

once

ntra

tion

(MIC

) Bre

akpo

ints

for H

aem

ophi

lus

spp.

Test

ing

Con

ditio

ns

Med

ium

:H

aem

ophi

lus

Test

Med

ium

(HTM

)In

ocul

um:

Dire

ct c

olon

y su

spen

sion

, equ

ival

ent t

o a

0.5

McF

arla

nd s

tand

ard

Incu

batio

n:35

°C

±2

degr

ees;

5%

CO

2; 1

6 to

18

hour

s

Min

imal

QC

Rec

omm

enda

tions

(See

Tab

le 3

Afo

r acc

epta

ble

QC

rang

es.)

Hae

mop

hilu

s in

fluen

zae

ATC

C®

4924

7H

aem

ophi

lus

influ

enza

e AT

CC

®49

766

Esch

eric

hia

coli

ATC

C®

352

18 (w

hen

test

ing

amox

icill

in-c

lavu

lani

c ac

id)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

tsR

I

S R

S

PEN

ICIL

LIN

SA

Am

pici

llin

10 µ

g≤

1819

-21

≥22

≥4

≤1

(5)

The

resu

lts o

f am

pici

llin

susc

eptib

ility

tes

ts s

houl

d be

used

to p

redi

ct th

e ac

tivity

of a

mox

icill

in. I

n m

ost c

ases

, adi

rect

β-la

ctam

ase

test

can

pro

vide

a r

apid

mea

ns o

fde

tect

ing

ampi

cilli

n an

d am

oxic

illin

resi

stan

ce. T

he m

ajor

ityof

isol

ates

of

H.

influ

enza

e th

at a

re r

esis

tant

to

ampi

cilli

nan

d am

oxic

illin

pro

duce

a T

EM

-type

β-la

ctam

ase.

(6)

R

are

β-la

ctam

ase-

nega

tive,

am

pici

llin-

resi

stan

t(B

LNA

R)

stra

ins

of H

. in

fluen

zae

shou

ld b

e co

nsid

ered

resi

stan

t to

am

oxic

illin

-cla

vula

nic

acid

, am

pici

llin-

sulb

acta

m,

cefa

clor

, ce

feta

met

, ce

foni

cid,

ce

fpro

zil,

cefu

roxi

me,

an

d lo

raca

rbef

de

spite

ap

pare

nt

in

vitro

susc

eptib

ility

of s

ome

BLN

AR

stra

ins

to th

ese

agen

ts.

Gen

eral

Com

men

ts

(1)O

nly

resu

lts o

f tes

ting

with

am

pici

llin,

one

of t

he th

ird-g

ener

atio

n ce

phal

ospo

rins,

chl

oram

phen

icol

, and

mer

open

em s

houl

d be

repo

rted

rout

inel

y w

ith C

SF

isol

ates

of H

aem

ophi

lus

influ

enza

e.

(2)A

mox

icill

in-c

lavu

lani

c ac

id, a

zith

rom

ycin

, cla

rithr

omyc

in, c

efac

lor,

cefp

rozi

l, lo

raca

rbef

, cef

dini

r, ce

fixim

e, c

efpo

doxi

me,

and

cef

urox

ime

axet

il ar

e or

al a

gent

s th

atm

ay b

e us

ed a

s em

piric

ther

apy

for r

espi

rato

ry tr

act i

nfec

tions

due

to H

aem

ophi

lus

spp.

The

resu

lts o

f sus

cept

ibili

ty te

sts

with

thes

e an

timic

robi

al a

gent

s ar

e of

ten

not u

sefu

l for

man

agem

ent o

f ind

ivid

ual p

atie

nts.

How

ever

, sus

cept

ibili

ty te

stin

g of

Hae

mop

hilu

ssp

p. w

ith th

ese

com

poun

ds m

ay b

e ap

prop

riate

for s

urve

illan

ceor

epi

dem

iolo

gic

stud

ies.

(3)T

o m

ake

HTM

: a fr

esh

hem

atin

sto

ck s

olut

ion

is p

repa

red

by d

isso

lvin

g 50

mg

of h

emat

in p

owde

r in

100

mL

of 0

.01

mol

/LN

aOH

with

hea

t and

stir

ring

until

the

pow

der

is t

horo

ughl

y di

ssol

ved.

The

n 30

mL

of t

he h

emat

in s

tock

sol

utio

n is

add

ed t

o 1

Lof

Mue

ller-

Hin

ton

agar

with

5 g

of

yeas

t ex

tract

als

o ad

ded.

Afte

rau

tocl

avin

g an

d co

olin

g, 3

mL

of a

n N

AD

sto

ck s

olut

ion

(50

mg

of N

AD

dis

solv

ed in

10

mL

of d

istil

led

wat

er, f

ilter

ste

riliz

ed) i

s ad

ded

asep

tical

ly.

(4) F

or s

ome

orga

nism

/ant

imic

robi

al a

gent

com

bina

tions

, th

e ab

senc

e of

res

ista

nt s

train

s pr

eclu

des

defin

ing

any

resu

lts c

ateg

orie

s ot

her

than

“su

scep

tible

.” F

orst

rain

s yi

eldi

ng r

esul

ts s

ugge

stiv

e of

a “

nons

usce

ptib

le”

cate

gory

, or

gani

sm i

dent

ifica

tion

and

antim

icro

bial

sus

cept

ibili

ty t

est

resu

lts s

houl

d be

con

firm

ed.

Sub

sequ

ently

, the

isol

ates

sho

uld

be s

aved

and

sub

mitt

ed to

a re

fere

nce

labo

rato

ry th

at w

ill c

onfir

m re

sults

usi

ng a

CLS

I/NC

CLS

refe

renc

e di

lutio

n m

etho

d .

NO

TE:I

nfor

mat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.


57

Tabl

e 2E

Hae

mop

hilu

sspp

.M

2-D

isk

Diff

usio

n


Tabl

e 2E

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

tsR

I

S R

S

ββ -LA

CTA

M/ββ

-LA

CTA

MA

SE IN

HIB

ITO

R C

OM

BIN

ATIO

NS

See

com

men

t (6)

.O O

Am

oxic

illin

-cla

vula

nic

acid

Am

pici

llin-

sulb

acta

m20

/10

µg10

/10

µg≤

19≤

19- -

≥20

≥20

≥8/

4≥

4/2

≤4/

2≤

2/1

CEP

HEM

S (P

AR

ENTE

RA

L) (

Incl

udin

g ce

phal

ospo

rins

I, II,

III,

and

IV. P

leas

e re

fer

to G

loss

ary

I.)S

ee c

omm

ent (

6).

B B B B

Cef

otax

ime

orce

ftazi

dim

e or

cefti

zoxi

me

orce

ftria

xone

30 µ

g30

µg

30 µ

g30

µg

- - - -

- - - -

≥26

≥26

≥26

≥26

- - - -

≤2

≤2

≤2

≤2

See

com

men

t (4)

.

B

Cef

urox

ime

sodi

um

(par

ente

ral)

30 µ

g≤

1617

-19

≥20

≥16

≤4

C

Cef

onic

id30

µg

≤16

17-1

9≥

20≥

16≤

4O

Cef

epim

e30

µg

- -

≥26

- ≤

2S

ee c

omm

ent (

4).

CEP

HEM

S (O

RA

L)S

ee c

omm

ent (

6).

C C C

Cef

aclo

r or

cefp

rozi

l or

lora

carb

ef

30 µ

g30

µg

30 µ

g

≤16

≤14

≤15

17-1

915

-17

16-1

8

≥20

≥18

≥19

≥32

≥32

≥32

≤8

≤8

≤8

C C C

Cef

dini

r or

cefix

ime

orce

fpod

oxim

e

5 µg

5 µg

10 µ

g

- - -

- - -

≥20

≥21

≥21

- - -

≤1

≤1

≤2

See

com

men

t (4)

.

CC

efur

oxim

e ax

etil

(ora

l)30

µg

≤16

17-1

9≥

20≥

16≤

4O

Cef

tibut

en30

µg

- -

≥28

- ≤

2S

ee c

omm

ent (

4).

Inv.

Cef

etam

et10

µg

≤14

15-1

7≥

18≥

16≤

4C

AR

BA

PEN

EMS

BM

erop

enem

10 µ

g-

- ≥

20-

≤0.

5S

ee c

omm

ent (

4).

C C

Erta

pene

m o

r im

ipen

em

10 µ

g10

µg

- -- -

≥19

≥16

- - ≤

0.5

≤4

See

com

men

t (4)

.

MO

NO

BA

CTA

MS

CA

ztre

onam

30 µ

g-

- ≥

26-

≤2

See

com

men

t (4)

.M

AC

RO

LID

ESC C

Azi

thro

myc

in o

rcl

arith

rom

ycin

15 µ

g15

µg

-≤

10-

11-1

2≥

12≥

13-

≥32

≤4

≤8

See

com

men

t (4)

.

KET

OLI

DES

CTe

lithr

omyc

in15

µg

≤11

12-1

4≥

15≥

16≤

4TE

TRA

CYC

LIN

ESC

Tetra

cycl

ine

30 µ

g≤

2526

-28

≥29

≥8

≤2

(7)

Org

anis

ms

that

are

sus

cept

ible

to te

tracy

clin

e ar

e al

soco

nsid

ered

sus

cept

ible

to d

oxyc

yclin

e an

d m

inoc

yclin

e.


Tabl

e 2E

Hae

mop

hilu

sspp

.M

2-D

isk

Diff

usio

n


Tabl

e 2E

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

ts

R

I S

R

S FL

UO

RO

QU

INO

LON

ES

C C C C C C C

Cip

roflo

xaci

n or

gatif

loxa

cin

orle

voflo

xaci

n or

lom

eflo

xaci

n or

mox

iflox

acin

or

oflo

xaci

nG

emifl

oxac

in

5 µg

5 µg

5 µg

10 µ

g5

µg5

µg5

µg

- - - - - - -

- - - - - - -

≥21

≥18

≥17

≥22

≥18

≥16

≥18

- - - - - - -

≤1

≤1

≤2

≤2

≤1

≤2

≤0.

12

See

com

men

t (4)

.

OG

repa

floxa

cin

5 µg

- -

≥24

- ≤

0.5

OTr

ovaf

loxa

cin

10 µ

g-

- ≥

22-

≤1

Inv.

Fler

oxac

in

5 µg

- -

≥19

-≤

2

FOLA

TE P

ATH

WAY

INH

IBIT

OR

SA

Trim

etho

prim

-su

lfam

etho

xazo

le1.

25/2

3.75

µg

≤10

11-1

5≥

16≥

4/76

≤0.

5/9.

5

PHEN

ICO

LS

BC

hlor

amph

enic

ol30

µg

≤25

26-2

8≥

29≥

8≤

2A

NSA

MYC

INS

CR

ifam

pin

5 µg

≤16

17-1

9≥

20≥

4 ≤

1


60

Tabl

e 2F

Nei

sser

ia g

onor

rhoe

aeM

2-D

isk

Diff

usio

n


Tabl

e 2F

. Zo

ne D

iam

eter

Inte

rpre

tive

Stan

dard

s an

d Eq

uiva

lent

Min

imal

Inhi

bito

ry C

once

ntra

tion

(MIC

) Bre

akpo

ints

for N

eiss

eria

gon

orrh

oeae

Test

ing

Con

ditio

ns

Med

ium

:G

C a

gar b

ase

and

1% d

efin

ed g

row

th s

uppl

emen

t.

The

use

of a

cys

tein

e-fre

e gr

owth

sup

plem

ent i

sno

t req

uire

d fo

r dis

k di

ffusi

on te

stin

g.In

ocul

um:

Dire

ct c

olon

y su

spen

sion

, equ

ival

ent t

o a

0.5

McF

arla

nd s

tand

ard.

Incu

batio

n:35

°C

±2

degr

ees;

5%

CO

2; 2

0 to

24

hour

s

Min

imal

QC

Rec

omm

enda

tions

(See

Tab

le 3

Afo

r acc

epta

ble

QC

rang

es.)

Nei

sser

ia g

onor

rhoe

aeAT

CC

®49

226

Gen

eral

Com

men

ts

(1)

For N

. gon

orrh

oeae

, an

inte

rmed

iate

resu

lt fo

r an

antim

icro

bial

age

nt in

dica

tes

eith

er a

tech

nica

l pro

blem

that

sho

uld

be re

solv

ed b

y re

peat

test

ing

or a

lack

of

clin

ical

exp

erie

nce

in tr

eatin

g or

gani

sms

with

thes

e zo

nes.

The

latte

r see

ms

to b

e th

e ca

se fo

r cef

met

azol

e, c

efot

etan

, cef

oxiti

n, a

nd s

pect

inom

ycin

. Stra

ins

with

inte

rmed

iate

zon

es w

ith th

e ot

her a

gent

s ha

ve a

doc

umen

ted

low

er c

linic

al c

ure

rate

(85

to 9

5%) c

ompa

red

to >

95%

for s

usce

ptib

le s

train

s.

(2)

Dis

k di

ffusi

on te

sts

with

am

pici

llin,

pen

icill

in, a

nd ri

fam

pin

for N

eiss

eria

men

ingi

tidis

are

unre

liabl

e. M

inim

al in

hibi

tory

con

cent

ratio

n (M

IC) t

ests

sho

uld

be u

sed

for t

hese

org

anis

ms.

(3)

The

reco

mm

ende

d m

ediu

m fo

r tes

ting

N. g

onor

rhoe

aeco

nsis

ts o

f GC

aga

r to

whi

ch a

1%

def

ined

gro

wth

sup

plem

ent (

1.1

g L-

cyst

eine

, 0.0

3 g

guan

ine

HC

L, 3

mg

thia

min

e H

CL,

13

mg

PAB

A, 0

.01

g B

12, 0

.1 g

coc

arbo

xyla

se, 0

.25

g N

AD

, 1 g

ade

nine

, 10

g L-

glut

amin

e, 1

00 g

glu

cose

, 0.0

2 g

ferr

ic n

itrat

e [in

1 L

H2O

])is

add

ed a

fter a

utoc

lavi

ng.

(4)

For

som

e or

gani

sm/a

ntim

icro

bial

age

nt c

ombi

natio

ns,

the

abse

nce

of r

esis

tant

stra

ins

prec

lude

s de

finin

g an

y re

sults

cat

egor

ies

othe

r th

an “

susc

eptib

le.”

For

stra

ins

yiel

ding

res

ults

sug

gest

ive

of a

“no

nsus

cept

ible

” ca

tego

ry,

orga

nism

ide

ntifi

catio

n an

d an

timic

robi

al s

usce

ptib

ility

tes

t re

sults

sho

uld

be c

onfir

med

.S

ubse

quen

tly, t

he is

olat

es s

houl

d be

sav

ed a

nd s

ubm

itted

to a

refe

renc

e la

bora

tory

that

will

con

firm

resu

lts u

sing

a C

LSI/N

CC

LS re

fere

nce

dilu

tion

met

hod.

NO

TE:

Info

rmat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.


61

Tabl

e 2F

Nei

sser

ia g

onor

rhoe

aeM

2-D

isk

Diff

usio

n


Tabl

e 2F

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

tsR

I

S R

S

PEN

ICIL

LIN

SC

Pen

icill

in10

uni

ts≤

2627

-46

≥47

≥2

≤0.

06(5

)

Apo

sitiv

e β-

lact

amas

e te

st

pred

icts

resi

stan

ce

to

peni

cilli

n,

ampi

cilli

n,

and

amox

icill

in.

(6)

Aβ-

lact

amas

e te

st w

ill d

etec

t on

e fo

rm o

fpe

nici

llin

resi

stan

ce in

N. g

onor

rhoe

aean

d al

som

ay

be

used

to

pr

ovid

e ep

idem

iolo

gic

info

rmat

ion.

St

rain

s w

ith

chro

mos

omal

lym

edia

ted

resi

stan

ce c

an b

e de

tect

ed o

nly

byth

e di

sk d

iffus

ion

met

hod

or t

he a

gar

dilu

tion

MIC

met

hod.

(7)

Gon

ococ

ci w

ith 1

0-un

it pe

nici

llin

disk

zon

edi

amet

ers

of

≤19

mm

ar

e lik

ely

to

be

β-la

ctam

ase-

prod

ucin

g st

rain

s. H

owev

er,

the

β-la

ctam

ase

test

re

mai

ns

pref

erab

le

to

othe

rsu

scep

tibili

ty

met

hods

fo

r ra

pid,

ac

cura

tere

cogn

ition

of

this

pla

smid

-med

iate

d pe

nici

llin

resi

stan

ce.

CEP

HEM

S (P

AR

ENTE

RA

L) (I

nclu

ding

cep

halo

spor

ins

I, II,

III,

and

IV. P

leas

e re

fer

to G

loss

ary

I.)C C C

Cef

otax

ime

orce

ftizo

xim

e or

ceftr

iaxo

ne

30 µ

g30

µg

30 µ

g

- - -

- - -

≥31

≥38

≥35

- - -

≤0.

5≤

0.5

≤0.

25

See

com

men

t (4)

.

C C C C

Cef

met

azol

eC

efot

etan

C

efox

itin

Cef

urox

ime

sodi

um

(par

ente

ral)

30 µ

g30

µg

30 µ

g30

µg

≤27

≤19

≤23

≤25

28-3

220

-25

24-2

726

-30

≥33

≥26

≥28

≥31

≥8

≥8

≥8

≥4

≤2

≤2

≤2

≤1

OC

efep

ime

30 µ

g-

- ≥

31-

≤0.

5S

ee c

omm

ent (

4).

OC

efta

zidi

me

30 µ

g-

- ≥

31-

≤0.

5S

ee c

omm

ent (

4).

CEP

HEM

S (O

RA

L)C C

C

efix

ime

or

cefp

odox

ime

5 µg

10 µ

g- -

- - ≥

31≥

29- -

≤0.

25≤

0.5

See

com

men

t (4)

.

Inv.

C

efet

amet

10 µ

g -

- ≥

29-

≤0.

5S

ee c

omm

ent (

4).

TETR

AC

YCLI

NES

C

Tetra

cycl

ine

30 µ

g≤

3031

-37

≥38

≥2

≤0.

25(8

) G

onoc

occi

with

30-

µg te

tracy

clin

e di

sk z

one

diam

eter

s of

≤19

mm

usu

ally

indi

cate

a p

lasm

id-

med

iate

d te

tracy

clin

e-re

sist

ant

N.

gono

rrhoe

ae(T

RN

G)

isol

ate.

Th

ese

stra

ins

shou

ld

beco

nfirm

ed b

y a

dilu

tion

test

(M

IC ≥

16 µ

g/m

L).

Ple

ase

refe

r to

Tabl

e 2F

in M

7.


62

Tabl

e 2F

Nei

sser

ia g

onor

rhoe

aeM

2-D

isk

Diff

usio

n


Tabl

e 2F

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

tsR

I

S R

S

FLU

OR

OQ

UIN

OLO

NES

C C C

Cip

roflo

xaci

n or

gatif

loxa

cin

orof

loxa

cin

5 µg

5 µg

5 µg

≤27

≤33

≤24

28-4

034

-37

25-3

0

≥41

≥38

≥31

≥1

≥0.

5≥

2

≤0.

06≤

0.12

≤0.

25

OE

noxa

cin

10 µ

g≤

3132

-35

≥36

≥2

≤0.

5O

Gre

paflo

xaci

n5

µg≤

2728

-36

≥37

≥1

≤0.

06O

Lom

eflo

xaci

n10

µg

≤26

27-3

7≥

38≥

2≤

0.12

OTr

ovaf

loxa

cin

10 µ

g-

-≥

34-

≤0.

25S

ee c

omm

ent (

4).

Inv.

Fler

oxac

in5

µg≤

2829

-34

≥35

≥1

≤0.

25A

MIN

OC

YCLI

TOLS

CSp

ectin

omyc

in10

0 µg

≤14

15-1

7≥

18≥

128

≤32


64

Tabl

e 2G

Stre

ptoc

occu

s pne

umon

iae

M2-

Dis

k D

iffus

ion


Tabl

e 2G

.Zo

ne D

iam

eter

Inte

rpre

tive

Stan

dard

s an

d Eq

uiva

lent

Min

imal

Inhi

bito

ry C

once

ntra

tion

(MIC

) Bre

akpo

ints

for

Stre

ptoc

occu

s pn

eum

onia

eTe

stin

g C

ondi

tions

Med

ium

:M

uelle

r-H

into

n ag

ar w

ith 5

% s

heep

blo

odIn

ocul

um:

Dire

ct c

olon

y su

spen

sion

, equ

ival

ent t

o a

0.5

McF

arla

nd s

tand

ard

Incu

batio

n:35

°C

±2

degr

ees;

5%

CO

2; 2

0 to

24

hour

s

Min

imal

QC

Rec

omm

enda

tions

(See

Tab

le 3

Afo

r acc

epta

ble

QC

rang

es.)

Stre

ptoc

occu

s pn

eum

onia

eAT

CC

® 4

9619

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

tsR

I

S R

S

PEN

ICIL

LIN

S(4

) Is

olat

es o

f pne

umoc

occi

with

oxa

cilli

n zo

ne s

izes

of ≥

20m

m a

re s

usce

ptib

le (M

IC ≤

0.06

µg/

mL)

to p

enic

illin

and

can

be

cons

ider

ed

susc

eptib

le

to

ampi

cilli

n,

amox

icill

in,

amox

icill

in-c

lavu

lani

c ac

id,

ampi

cilli

n-su

lbac

tam

, ce

facl

or,

cefd

inir,

cef

epim

e, c

efet

amet

, cef

ixim

e, c

efot

axim

e, c

efpr

ozil,

cefti

bute

n, c

eftri

axon

e, c

efur

oxim

e, c

efpo

doxi

me,

cef

tizox

ime,

erta

pene

m,

imip

enem

, lo

raca

rbef

, an

d m

erop

enem

fo

rap

prov

ed in

dica

tions

, and

thes

e ag

ents

nee

d no

t be

test

ed.

AP

enic

illin

1 µg

oxa

cilli

n-

- ≥

20-

≤0.

06(5

) P

enic

illin

, m

erop

enem

, an

d ce

fota

xim

e or

cef

triax

one

MIC

s sh

ould

be

dete

rmin

ed fo

r th

ose

isol

ates

with

oxa

cilli

nzo

ne s

izes

≤19

mm

, bec

ause

zon

es o

f ≤1

9 m

m o

ccur

with

peni

cilli

n-re

sist

ant,

inte

rmed

iate

, or

ce

rtain

su

scep

tible

stra

ins.

Isol

ates

sho

uld

not b

e re

porte

d as

pen

icill

in-r

esis

tant

or in

term

edia

te b

ased

sol

ely

on a

n ox

acill

in z

one

≤19

mm

.

Gen

eral

Com

men

ts

(1)

Am

oxic

illin

, am

pici

llin,

cef

epim

e, c

efot

axim

e, c

eftri

axon

e, c

efur

oxim

e, e

rtape

nem

, im

ipen

em, a

nd m

erop

enem

may

be

used

to tr

eat p

neum

ococ

cal i

nfec

tions

;ho

wev

er, r

elia

ble

disk

diff

usio

n su

scep

tibili

ty te

sts

with

thes

e ag

ents

do

not y

et e

xist

. The

ir in

vitr

oac

tivity

is b

est d

eter

min

ed u

sing

an

MIC

met

hod.

(2)

Pen

icill

in, c

efot

axim

e or

cef

triax

one,

and

mer

open

em s

houl

d be

test

ed b

y a

relia

ble

MIC

met

hod

(suc

h as

that

des

crib

ed in

CLS

I/NC

CLS

doc

umen

t M7)

and

repo

rted

rout

inel

y w

ith C

SF

isol

ates

of S

. pne

umon

iae.

Suc

h is

olat

es s

houl

d al

so b

e te

sted

aga

inst

van

com

ycin

usi

ng th

e M

IC o

r dis

k m

etho

d.

(3)

For s

ome

orga

nism

/ant

imic

robi

al a

gent

com

bina

tions

, the

abs

ence

of r

esis

tant

stra

ins

prec

lude

s de

finin

g an

y re

sults

cat

egor

ies

othe

r tha

n “s

usce

ptib

le.”

For

stra

ins

yiel

ding

res

ults

sug

gest

ive

of a

“no

nsus

cept

ible

” ca

tego

ry,

orga

nism

iden

tific

atio

n an

d an

timic

robi

al s

usce

ptib

ility

tes

t re

sults

sho

uld

be c

onfir

med

.S

ubse

quen

tly, t

he is

olat

es s

houl

d be

sav

ed a

nd s

ubm

itted

to a

refe

renc

e la

bora

tory

that

will

con

firm

resu

lts u

sing

a C

LSI/N

CC

LS re

fere

nce

dilu

tion

met

hod.

NO

TE:

Info

rmat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.


65

Tabl

e 2G

Stre

ptoc

occu

s pne

umon

iae

M2-

Dis

k D

iffus

ion


Tabl

e 2G

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

tsR

I

S R

S

GLY

CO

PEPT

IDES

BVa

ncom

ycin

30 µ

g-

- ≥

17-

≤1

(6)

No

S. p

neum

onia

est

rain

with

a v

anco

myc

inzo

ne d

iam

eter

<17

mm

has

bee

n ob

serv

ed;

subm

it su

ch s

train

s to

a re

fere

nce

labo

rato

ry.

MA

CR

OLI

DES

(7) S

usce

ptib

ility

and

resi

stan

ce to

azith

rom

ycin

, cla

rithr

omyc

in, a

nd d

irith

rom

ycin

can

be p

redi

cted

by

usin

g er

ythr

omyc

in.

(8)

Not

rou

tinel

y re

porte

d on

isol

ates

fro

m t

heur

inar

y tra

ct.

AE

ryth

rom

ycin

15 µ

g ≤

1516

-20

≥21

≥

1≤

0.25

OA

zith

rom

ycin

15

µg

≤13

14-1

7≥

18≥

2 ≤

0.5

OC

larit

hrom

ycin

15 µ

g≤

1617

-20

≥21

≥1

≤0.

25O

Diri

thro

myc

in15

µg

≤13

14

-17

≥18

≥2

≤0.

5K

ETO

LID

ESB

Telit

hrom

ycin

15 µ

g≤

1516

-18

≥19

≥

4 ≤

1TE

TRA

CYC

LIN

ESB

Tetra

cycl

ine

30 µ

g≤

1819

-22

≥23

≥8

≤2

(9)

Org

anis

ms

that

ar

e su

scep

tible

to

tetra

cycl

ine

are

also

con

side

red

susc

eptib

le t

odo

xycy

clin

e an

d m

inoc

yclin

e.FL

UO

RO

QU

INO

LON

ESB B B B B

B

Gat

iflox

acin

Gem

iflox

acin

Le

voflo

xaci

nM

oxifl

oxac

inSp

arflo

xaci

nO

floxa

cin

5 µg

5 µg

5 µg

5 µg

5 µg

5

µg

≤17

≤19

≤

13≤

14≤

15≤

12

18-2

020

-22

14-1

615

-17

16-1

813

-15

≥21

≥23

≥17

≥18

≥19

≥16

≥4

≥0.

5≥

8≥

4≥

2≥

8

≤1

≤0.

12≤

2≤

1≤

0.5

≤2

OG

repa

floxa

cin

5 µg

≤15

16-1

8≥

19≥

2≤

0.5

OTr

ovaf

loxa

cin

10 µ

g≤

1516

-18

≥19

≥4

≤1

FOLA

TE P

ATH

WAY

INH

IBIT

OR

SA

Trim

etho

prim

-su

lfam

etho

xazo

le1.

25/

23.7

5 µg

≤15

16-1

8≥

19≥

4/76

≤

0.5/

9.5

PHEN

ICO

LSC

Chl

oram

phen

icol

30

µg

≤20

- ≥

21≥

8≤

4S

ee c

omm

ent (

8).

AN

SAM

YCIN

SC

R

ifam

pin

5 µg

≤16

17-1

8≥

19≥

4≤

1 (1

0)R

x:R

ifam

pin

shou

ld n

ot b

e us

ed a

lone

for c

hem

othe

rapy

.LI

NC

OSA

MID

ESB

Clin

dam

ycin

2 µg

≤

1516

-18

≥19

≥1

≤0.

25S

ee c

omm

ent (

8).

STR

EPTO

GR

AM

INS

OQ

uinu

pris

tin-d

alfo

pris

tin

15 µ

g ≤

15

16-1

8≥

19≥

4 ≤

1O

XAZO

LID

INO

NES

CLi

nezo

lid30

µg

--

≥21

-≤

2S

ee c

omm

ent (

3).


66

Tabl

e 2H

Stre

ptoc

occu

sspp

. O

ther

Tha

n S.

pne

umon

iae

M2-

Dis

k D

iffus

ion


Tabl

e 2H

. Zo

ne D

iam

eter

Inte

rpre

tive

Stan

dard

s an

d Eq

uiva

lent

Min

imal

Inhi

bito

ry C

once

ntra

tion

(MIC

) Bre

akpo

ints

forS

trep

toco

ccus

spp.

Oth

erTh

an S

trep

toco

ccus

pne

umon

iae

Test

ing

Con

ditio

ns

Med

ium

:M

uelle

r-H

into

n ag

ar w

ith 5

% s

heep

blo

odIn

ocul

um:

Dire

ct c

olon

y su

spen

sion

, equ

ival

ent t

o a

0.5

McF

arla

nd s

tand

ard

Incu

batio

n:35

°C

±2

degr

ees;

5%

CO

2;20

to 2

4 ho

urs

Min

imal

QC

Rec

omm

enda

tions

(See

Tab

le 3

Afo

r acc

epta

ble

QC

rang

es.)

Stre

ptoc

occu

s pn

eum

onia

eAT

CC

®49

619

Gen

eral

Com

men

ts

(1)

For

this

tabl

e, th

e be

ta-h

emol

ytic

gro

up in

clud

es th

e la

rge-

colo

ny-fo

rmin

g py

ogen

ic s

train

s of

stre

ptoc

occi

with

Gro

up A

(S. p

yoge

nes)

, C, o

r G

ant

igen

s an

dst

rain

s w

ith G

roup

B (S

. aga

lact

iae)

ant

igen

. Sm

all-c

olon

y-fo

rmin

g be

ta-h

emol

ytic

stra

ins

with

Gro

up A

, C, F

, or G

ant

igen

s (S

. ang

inos

us, p

revi

ousl

y te

rmed

“S.

mille

ri”)

are

cons

ider

ed p

art o

f the

viri

dans

gro

up, a

nd in

terp

retiv

e cr

iteria

for

the

virid

ans

grou

p sh

ould

be

used

. The

viri

dans

gro

up a

lso

incl

udes

S. m

itis,

S.

oral

is, S

. san

guis

, S. s

aliv

ariu

s, S

. int

erm

ediu

s, S

. con

stel

latu

s, S

. mut

ans,

and

S. b

ovis

.

(2)

Virid

ans

stre

ptoc

occi

isol

ated

from

nor

mal

ly s

teril

e bo

dy s

ites

(e.g

., ce

rebr

ospi

nal f

luid

, blo

od, b

one)

sho

uld

be te

sted

for

peni

cilli

n su

scep

tibili

ty u

sing

an

MIC

met

hod.

(3)

Sus

cept

ibili

ty te

stin

g of

pen

icill

ins

and

othe

r β-la

ctam

s ap

prov

ed b

y FD

Afo

r tre

atm

ent o

f Stre

ptoc

occu

s py

ogen

esor

Stre

ptoc

occu

s ag

alac

tiae

is n

ot n

eces

sary

for c

linic

al p

urpo

ses

and

need

not

be

done

rout

inel

y, s

ince

as

with

van

com

ycin

, res

ista

nt s

train

s ha

ve n

ot b

een

reco

gniz

ed.

Inte

rpre

tive

crite

ria a

re p

rovi

ded

for

phar

mac

eutic

al d

evel

opm

ent,

epid

emio

logy

, or

mon

itorin

g fo

r em

ergi

ng r

esis

tanc

e. A

ny s

train

fou

nd t

o be

non

susc

eptib

le s

houl

d be

ref

erre

d to

a r

efer

ence

labo

rato

ry fo

r con

firm

atio

n.

(4)

Inte

rpre

tive

crite

ria fo

r st

rept

ococ

ci a

re p

ropo

sed

base

d on

pop

ulat

ion

dist

ribut

ions

of v

ario

us s

peci

es, p

harm

acok

inet

ics

of th

e an

timic

robi

al a

gent

s, p

revi

ousl

ypu

blis

hed

liter

atur

e, a

nd th

e cl

inic

al e

xper

ienc

e of

cer

tain

mem

bers

of t

he s

ubco

mm

ittee

. Sys

tem

atic

ally

col

lect

ed c

linic

al d

ata

wer

e no

t ava

ilabl

e fo

r rev

iew

with

man

y of

the

com

poun

ds in

the

grou

p.

(5)

For

som

e or

gani

sm/a

ntim

icro

bial

age

nt c

ombi

natio

ns,

the

abse

nce

of r

esis

tant

stra

ins

prec

lude

s de

finin

g an

y re

sults

cat

egor

ies

othe

r th

an “

susc

eptib

le.”

For

stra

ins

yiel

ding

res

ults

sug

gest

ive

of a

“no

nsus

cept

ible

” ca

tego

ry,

orga

nism

ide

ntifi

catio

n an

d an

timic

robi

al s

usce

ptib

ility

tes

t re

sults

sho

uld

be c

onfir

med

.S

ubse

quen

tly, t

he is

olat

es s

houl

d be

sav

ed a

nd s

ubm

itted

to a

refe

renc

e la

bora

tory

that

will

con

firm

resu

lts u

sing

a C

LSI/N

CC

LS re

fere

nce

dilu

tion

met

hod.

NO

TE:

Info

rmat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.


67

Tabl

e 2H

Stre

ptoc

occu

sspp

. O

ther

Tha

n S.

pne

umon

iae

M2-

Dis

k D

iffus

ion


Tabl

e 2H

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

tsR

I

S R

S

PEN

ICIL

LIN

S(6

) A

stre

ptoc

occa

l iso

late

that

is s

usce

ptib

le to

pen

icill

inca

n be

con

side

red

susc

eptib

le t

o am

pici

llin,

am

oxic

illin

,am

oxic

illin

-cla

vula

nic

acid

, am

pici

llin-

sulb

acta

m, c

efac

lor,

cefa

zolin

, ce

fdin

ir,

cefe

pim

e,

cefp

rozi

l, ce

fota

xim

e,ce

ftibu

ten

(Gro

up A

stre

ptoc

occi

on

ly),

ceftr

iaxo

ne,

cefu

roxi

me,

ce

fpod

oxim

e,

cefti

zoxi

me,

ce

phal

othi

n,ce

phap

irin,

ce

phra

dine

, im

ipen

em,

lora

carb

ef,

and

mer

open

em f

or a

ppro

ved

indi

catio

ns,

and

need

not

be

test

ed a

gain

st th

ose

agen

ts.

A AP

enic

illin

(bet

a-he

mol

ytic

gro

up) o

ram

pici

llin

(bet

a-he

mol

ytic

gro

up)

10 u

nits

10 µ

g- -

- - ≥

24≥

24- -

≤0.

12≤

0.25

(7) B

reak

poin

ts a

re fo

r bet

a-he

mol

ytic

stre

ptoc

occi

onl

y.P

enic

illin

, am

pici

llin,

and

oxa

cilli

n di

sk d

iffus

ion

test

ing

isno

t rel

iabl

e w

ith v

irida

ns s

trept

ococ

ci.

See

com

men

t (5)

.C

EPH

EMS

(PA

REN

TER

AL)

(In

clud

ing

ceph

alos

porin

s I,

II, II

I, an

d IV

. Ple

ase

refe

r to

Glo

ssar

y I.)

S

ee c

omm

ent (

6).

C C C C C C

Cef

epim

e (b

eta-

hem

olyt

ic g

roup

)or ce

fota

xim

e (b

eta-

hem

olyt

ic g

roup

)or ce

ftria

xone

(bet

a-he

mol

ytic

gro

up)

Cef

epim

e (v

irida

ns g

roup

) or

cefo

taxi

me

(viri

dans

gro

up) o

rce

ftria

xone

(viri

dans

gro

up)

30 µ

g

30 µ

g

30 µ

g

30 µ

g30

µg

30 µ

g

- - -

≤21

≤25

≤24

- - -

22-2

326

-27

25-2

6

≥24

≥24

≥24

≥24

≥28

≥27

- - - ≥4

≥4

≥4

≤0.

5

≤0.

5

≤0.

5

≤1

≤1

≤1

See

com

men

t (5)

.

GLY

CO

PEPT

IDES

BVa

ncom

ycin

30 µ

g-

-≥

17-

≤1

See

com

men

t (5)

.LI

POPE

PTID

ESC

Dap

tom

ycin

30 µµ

g-

-≥≥

16-

≤≤1

See

com

men

t (5)

.M

AC

RO

LID

ES(8

) Su

scep

tibilit

y an

d re

sist

ance

to a

zith

rom

ycin

, cla

rithr

o-m

ycin

, an

d di

rithr

omyc

in

can

be

pred

icte

d by

te

stin

ger

ythr

omyc

in.

(9)

Not

rout

inel

y re

porte

d on

isol

ates

from

the

urin

ary

tract

.A

Ery

thro

myc

in15

µg

≤15

16-2

0≥

21≥

1≤

0.25

(10)

R

x:

Rec

omm

enda

tions

fo

r in

trap

artu

mpr

ophy

laxi

s fo

r G

roup

B s

trep

toco

cci a

re p

enic

illin

or

ampi

cilli

n.

Whi

le

cefa

zolin

is

re

com

men

ded

for

peni

cilli

n-al

lerg

ic w

omen

at

low

ris

k fo

r an

aphy

laxi

s,th

ose

at

high

ri

sk

for

anap

hyla

xis

may

re

ceiv

ecl

inda

myc

in o

r er

ythr

omyc

in.

Gro

up B

str

epto

cocc

iar

e su

scep

tible

to a

mpi

cilli

n, p

enic

illin

, and

cef

azol

in,

but

may

be

re

sist

ant

to

clin

dam

ycin

an

d/or

eryt

hrom

ycin

. W

hen

a G

roup

B

st

rept

ococ

cus

isis

olat

ed fr

om a

pre

gnan

t wom

an w

ith s

ever

e pe

nici

llin

alle

rgy

(hig

h ris

k fo

r an

aphy

laxi

s),

clin

dam

ycin

and

eryt

hrom

ycin

sho

uld

be te

sted

and

rep

orte

d.


68

Tabl

e 2H

Stre

ptoc

occu

sspp

. O

ther

Tha

n S.

pne

umon

iae

M2-

Dis

k D

iffus

ion


Tabl

e 2H

. (C

ontin

ued)

Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

tsR

I

S R

S

MA

CR

OLI

DES

(Con

tinue

d)O

A

zith

rom

ycin

15 µ

g≤

1314

-17

≥18

≥2

≤0.

5O

C

larit

hrom

ycin

15 µ

g≤

1617

-20

≥21

≥1

≤0.

25O

D

irith

rom

ycin

15 µ

g≤

1314

-17

≥18

≥2

≤0.

5TE

TRA

CYC

LIN

ESO

Te

tracy

clin

e 30

µg

≤18

19-2

2≥

23≥

8≤

2(1

1)

Org

anis

ms

that

are

sus

cept

ible

to

tetra

cycl

ine

are

also

cons

ider

ed s

usce

ptib

le to

dox

ycyc

line

and

min

ocyc

line.

FLU

OR

OQ

UIN

OLO

NES

CLe

voflo

xaci

n5

µg≤

1314

-16

≥17

≥8

≤2

(12)

B

reak

poin

ts

are

for

repo

rting

ag

ains

t be

ta-h

emol

ytic

stre

ptoc

occi

onl

y.C

Oflo

xaci

n5

µg≤

1213

-15

≥16

≥8

≤2

See

com

men

t (12

).O

Gat

iflox

acin

5 µg

≤17

18

-20

≥21

≥4

≤1

See

com

men

t (12

).O

Gre

paflo

xaci

n5

µg≤

1516

-18

≥19

≥2

≤0.

5O

Trov

aflo

xaci

n10

µg

≤15

16-1

8≥

19

≥4

≤1

PHEN

ICO

LSB

Chl

oram

phen

icol

30 µ

g≤

1718

-20

≥21

≥16

≤4

See

com

men

t (9)

.LI

NC

OSA

MID

ESB

Clin

dam

ycin

2 µg

≤15

16-1

8≥

19≥

1≤

0.25

See

com

men

ts (6

)and

(10)

.(1

3)

Mac

rolid

e-re

sist

ant

isol

ates

of

be

ta-h

emol

ytic

stre

ptoc

occi

may

hav

e co

nstit

utiv

e or

indu

cibl

e re

sist

ance

to c

linda

myc

in [m

ethy

latio

n of

the

23S

rRN

Aen

code

d by

an

erm

gene

als

o re

ferr

ed to

as

MLS

B(m

acro

lide,

linc

osam

ide,

and

type

B s

trep

togr

amin

) re

sist

ance

] or

may

be

resi

stan

ton

ly t

o m

acro

lides

(ef

flux

mec

hani

sm e

ncod

ed b

y a

mef

gene

). In

duci

ble

clin

dam

ycin

res

ista

nce

can

be d

etec

ted

usin

g a

disk

ap

prox

imat

ion

test

by

pl

acin

g a

2-µg

clin

dam

ycin

di

sk

12

mm

fr

om

the

edge

of

a

15-µ

ger

ythr

omyc

in d

isk

as p

art

of t

he n

orm

al d

isk

diffu

sion

proc

edur

e. F

ollo

win

g in

cuba

tion,

org

anis

ms

that

do

not

show

flat

teni

ng o

f the

clin

dam

ycin

zon

e sh

ould

be

repo

rted

as

clin

dam

ycin

su

scep

tible

. O

rgan

ism

s th

at

show

flatt

enin

g of

th

e cl

inda

myc

in

zone

ad

jace

nt

to

the

eryt

hrom

ycin

di

sk

(ref

erre

d to

as

a

“D”

zone

) ha

vein

duci

ble

clin

dam

ycin

res

ista

nce.

Suc

h is

olat

es s

houl

d be

repo

rted

as

“clin

dam

ycin

res

ista

nt.”

Aco

mm

ent t

hat “

This

isol

ate

is p

resu

med

to

be r

esis

tant

bas

ed o

n de

tect

ion

ofin

duci

ble

clin

dam

ycin

res

ista

nce.

Clin

dam

ycin

may

stil

l be

effe

ctiv

e in

som

e pa

tient

s.”

may

be

incl

uded

.ST

REP

TOG

RA

MIN

SC

Qui

nupr

istin

-dal

fopr

istin

15 µ

g ≤

1516

-18

≥19

≥4

≤1

(14)

B

reak

poin

ts a

re f

or r

epor

ting

agai

nst

Stre

ptoc

occu

spy

ogen

eson

ly.O

XAZO

LID

INO

NES

CLi

nezo

lid30

µg

--

≥21

-≤

2S

ee c

omm

ent (

5).



Test

/Rep

ort

Gro

up

Ant

imic

robi

al

Age

nt

Dis

k C

onte

nt

Zone

Dia

met

er,

Nea

rest

Who

le m

m

Equi

vale

nt M

ICB

reak

poin

ts (µµ

g/m

L)

Com

men

tsR

I

S R

S

PEN

ICIL

LIN

SA

Am

pici

llin

10 µ

g≤

1314

-16

≥17

≥32

≤8

(2)

Cla

ss

repr

esen

tativ

e fo

r am

pici

llin

and

amox

icill

in.

TETR

AC

YCLI

NES

CTe

tracy

clin

e30

µg

≤14

15-1

8≥

19≥

16≤

4(3

) Te

tracy

clin

e re

sults

can

be

used

to p

redi

ctth

e lik

ely

susc

eptib

ility

of i

sola

tes

todo

xycy

clin

e; d

o no

t use

dis

k te

st fo

rdo

xycy

clin

e, a

s th

ere

is p

oor c

orre

latio

n w

ithM

IC re

sults

.FO

LATE

PAT

HW

AYIN

HIB

ITO

RS

BTr

imet

hopr

im-s

ulfa

met

hoxa

zole

1.25

/23.

75 µ

g≤

1011

-15

≥16

≥8/

152

≤2/

38C

Sul

fona

mid

es25

0 µg

or

300

µg≤

1213

-16

≥17

≥35

0≤

100

(4)

The

sulfi

soxa

zole

dis

k ca

n be

use

d to

repr

esen

t any

of t

he c

urre

ntly

ava

ilabl

esu

lfona

mid

e pr

epar

atio

ns.

PHEN

ICO

LSC

Chl

oram

phen

icol

30 µ

g≤

1213

-17

≥18

≥32

≤8

(5)

Use

with

cau

tion

as d

isk

diffu

sion

test

may

mis

clas

sify

man

y or

gani

sms

(hig

her m

inor

err

orra

te).

Gen

eral

Com

men

ts

(1)

The

resu

lts o

f di

sk d

iffus

ion

test

s fo

r am

pici

llin,

tet

racy

clin

e, t

rimet

hopr

im-s

ulfa

met

hoxa

zole

, an

d su

lfona

mid

es (

i.e.,

perc

enta

ge o

f su

scep

tible

,in

term

edia

te, a

nd re

sist

ant)

corr

elat

e w

ell w

ith re

sults

det

erm

ined

by

brot

h m

icro

dilu

tion.

Dis

k di

ffusi

on te

sts

shou

ld n

ot b

e us

ed fo

r ery

thro

myc

in, b

ecau

seth

ere

is a

poo

r cor

rela

tion

with

MIC

resu

lts.

NO

TE:

Info

rmat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.

Min

imal

QC

Rec

omm

enda

tions

(See

Tab

le 3

for a

ccep

tabl

e Q

C ra

nges

.)

Esch

eric

hia

coli

ATC

C®

2592

2

Test

ing

Con

ditio

ns

Med

ium

:M

uelle

r-H

into

n ag

arIn

ocul

um:

Gro

wth

met

hod

or d

irect

col

ony

susp

ensi

on,

equi

vale

nt to

a 0

.5 M

cFar

land

sta

ndar

d.In

cuba

tion:

35 °

C ±

2 de

gree

s; a

mbi

ent a

ir; 1

6 to

18

hour

s

Tabl

e 2I

. Zo

ne D

iam

eter

Inte

rpre

tive

Stan

dard

s an

d Eq

uiva

lent

Min

imal

Inhi

bito

ry C

once

ntra

tion

(MIC

) Bre

akpo

ints

for V

ibrio

cho

lera

e

Tabl

e 2I

Vibr

io c

hole

rae

M2-

Dis

k D

iffus

ion



Tabl

e 3

Non

fast

idio

us Q

ualit

y C

ontro

lM

2-D

isk

Diff

usio

n

Table 3. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of Disk DiffusionTesting of Nonfastidious Organisms (Using Mueller-Hinton Medium Without Blood or OtherSupplements)

AntimicrobialAgent

Disk ContentEscherichia

coliATCC® 25922a

Staphylococcusaureus

ATCC® 25923

Pseudomonasaeruginosa

ATCC® 27853

Escherichiacoli

ATCC® 35218b

AmikacinAmoxicillin-clavulanic acidAmpicillinAmpicillin-sulbactamAzithromycinAzlocillinAztreonamCarbenicillinCefaclorCefamandoleCefazolinCefdinirCefditorenCefepimeCefetametCefiximeCefmetazoleCefonicidCefoperazoneCefotaximeCefotetanCefoxitin Cefpodoxime CefprozilCeftazidimeCeftibutenCeftizoximeCeftriaxoneCefuroximeCephalothinChloramphenicolCinoxacinCiprofloxacinClarithromycinClinafloxacinClindamycinc

ColistinDaptomycind

DirithromycinDoripenemDoxycyclineEnoxacinErtapenemErythromycinc

FleroxacinFosfomycine

GarenoxacinGatifloxacinGemifloxacinGentamicinfGrepafloxacinImipenemKanamycinLevofloxacinLinezolidLomefloxacinLoracarbefMecillinam

30 µg 20/10 µg

10 µg10/10 µg

15 µg75 µg30 µg

100 µg30 µg30 µg30 µg5 µg5 µg30 µg10 µg5 µg30 µg30 µg75 µg30 µg30 µg30 µg10 µg30 µg30 µg30 µg30 µg30 µg30 µg30 µg30 µg

100 µg5 µg15 µg5 µg2 µg

10 µµg30 µg15 µg10 µµg30 µg10 µg10 µg15 µg5 µg

200 µg5 µg5 µg5 µg10 µg5 µg10 µg30 µg5 µg30 µg10 µg30 µg10 µg

19-26 18-2416-2219-24

--

28-3623-2923-2726-3221-2724-2822-2831-3724-2923-2726-3225-2928-3429-3528-3423-2923-2821-2725-3227-3530-3629-3520-2615-2121-2726-3230-40

-31-40

-11-17

--

28-3518-2428-3629-36

-28-3422-3028-3530-3729-3619-2628-3626-3217-2529-37

-27-3323-2924-30

20-26 28-3627-3529-3721-26

---

27-3126-3429-3525-3220-2823-29

--

25-3422-2824-3325-3117-2323-2919-2527-3316-20

-27-3522-2827-3529-3719-26

-22-3026-3228-3724-30

-18-2318-2633-4223-2922-2824-3122-3021-2725-3330-3627-3327-3319-2726-31

-19-2625-3025-3223-2923-31

-

18-26----

24-3023-2918-24

-----

24-30----

23-2918-22

----

22-29-

12-1717-23

----

25-33-

27-35-

11-17--

29-35-

22-2813-21

-12-20

-19-2520-2819-2516-2120-2720-28

-19-26

-22-28

--

-17-22

613-19

---------------------------------------

---------------



NOTE: Information in boldface type is considered tentative for one year.

Footnotes

a. ATCC is a registered trademark of the American Type Culture Collection.b. Careful organism maintenance is required; refer to M2, Section 10.3.c. When disk approximation tests are performed with erythromycin and clindamycin, S. aureus ATCC® BAA-

977 (containing inducible ermA-mediated resistance) and S. aureus ATCC® BAA-976 (containing msrA-mediated macrolide-only efflux) are recommended for quality assessment purposes (e.g., training,competency assessment, or test evaluation). S. aureus ATCC® BAA-977 should demonstrate inducibleclindamycin resistance (i.e., a positive D-zone test), while S. aureus ATCC® BAA-976 should notdemonstrate inducible clindamycin resistance. S. aureus ATCC® 25923 should be used for routine qualitycontrol (e.g., weekly or daily) of erythromycin and clindamycin disks using standard Mueller-Hinton agar.

d. Some lots of Mueller-Hinton agar are deficient in calcium and give small zones.e. The 200-µg fosfomycin disk contains 50 µg of glucose-6-phosphate.f. For control limits of gentamicin 120-µg and streptomycin 300-µg disks, use Enterococcus faecalis ATCC® 29212

(gentamicin: 16 to 23 mm; streptomycin: 14 to 20 mm).g. These agents can be affected by excess levels of thymidine and thymine. See M2, Section 4.1.4 for guidance should

a problem with quality control occur.


AntimicrobialAgent Disk Content

Escherichiacoli

ATCC® 25922a


ATCC® 25923


ATCC® 27853

Escherichiacoli

ATCC® 35218b

MeropenemMethicillinMezlocillinMinocyclineMoxalactamMoxifloxacinNafcillinNalidixic acidNetilmicinNitrofurantoinNorfloxacinOfloxacinOxacillinPenicillinPiperacillinPiperacillin-tazobactamPolymyxin BQuinupristin-dalfopristinRifampinSparfloxacinStreptomycinf

Sulfisoxazoleg

TeicoplaninTelavancinTelithromycinTetracyclineTicarcillinTicarcillin-clavulanic acidTigecyclineTobramycinTrimethoprimg

Trimethoprim-sulfamethoxazoleg

TrospectomycinTrovafloxacinVancomycin

10 µg5 µg75 µg30 µg30 µg5 µg1 µg30 µg30 µg

300 µg10 µg5 µg1 µg

10 units100 µg

100/10 µg300 units


250 µg or 300 µg30 µg30 µµg15 µg30 µg75 µg

75/10 µg15 µµg10 µg5 µg

1.25/23.75 µg30 µg10 µg30 µg

28-34-

23-2919-2528-3528-35

-22-2822-3020-2528-3529-33

--

24-3024-3013-19

-8-10

30-3812-2015-23

---

18-2524-3024-3020-2718-2621-2823-2910-1629-36

-

29-3717-22

-25-3018-2428-3516-22

-22-3118-2217-2824-2818-2426-37

-27-36

-21-2826-3427-3314-2224-3415-2116-2024-3024-30

-29-3720-2519-2919-2624-3215-2029-3517-21

27-33-

19-25-

17-2517-25

--

17-23-

22-2917-21

--

25-3325-3314-18

--

21-29------

21-2720-289-13

19-25---

21-27-

--------------

12-1824-30

----------6

21-25- ------

Tabl

e 3

Non

fast

idio

us Q

ualit

y C

ontro

lM

2-D

isk

Diff

usio

n

Tabl

e 3A

Fast

idio

us Q

ualit

y C

ontro

lM

2-D

isk

Diff

usio

nJanuary 2005 Vol. 25 No. 1


Table 3A. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of DiskDiffusion Testing of Fastidious Organisms


Haemophilusinfluenzae ATCC®

49247a

Haemophilusinfluenzae

ATCC® 49766

Neisseria gonorrhoeae ATCC® 49226

Streptococcuspneumoniae

ATCC® 49619b

Amoxicillin-clavulanic acidc

AmpicillinAmpicillin-sulbactamAzithromycinAztreonamCefaclorCefdinirCefditorenCefepimeCefetametCefiximeCefmetazoleCefonicidCefotaximeCefotetanCefoxitinCefpodoximeCefprozilCeftazidimeCeftibutenCeftizoximeCeftriaxoneCefuroximeCephalothinChloramphenicolCiprofloxacinClarithromycinClinafloxacinClindamycinDaptomycind

DirithromycinDoripenemEnoxacinErtapenemErythromycinFleroxacinGarenoxacinGatifloxacin Gemifloxacin Grepafloxacin ImipenemLevofloxacinLinezolidLomefloxacinLoracarbefMeropenemMoxifloxacinNitrofurantoinNorfloxacinOfloxacinOxacillinPenicillinPiperacillin-tazobactamQuinupristin-dalfopristinRifampin

20/10 µg10 µg

10/10 µg15 µg30 µg30 µg5 µg5 µg

30 µg10 µg5 µg

30 µg30 µg30 µg30 µg30 µg10 µg30 µg30 µg30 µg30 µg30 µg30 µg30 µg30 µg5 µg

15 µg5 µg2 µg

30 µg15 µg10 µµg10 µg10 µg15 µg5 µg5 µg5 µg5 µg5 µg

10 µg5 µg 30 µg10 µg30 µg10 µg5 µg


10 units100/10 µg

15 µg5 µg

15-2313-2114-2213-2130-38

--

25-3425-3123-2825-3316-21

-31-39

--

25-31-

27-3529-3629-3931-39

--

31-4034-4211-1734-43

---

21-31-

20-28-

30-3833-4133-4130-3732-3921-2932-40

- 33-41

-20-2831-39

--

31-40--

33-3815-2122-30

-----

25-3124-31

-----

30-38----

20-27----

28-36----------

27-33----------

26-32----------

------

40-49-

37-4635-4337-4531-36

-38-4830-3633-4135-43

-35-43

-42-5139-5133-41

--

48-58------

43-51--

43-51-

45-56 -

44-52 ---

45-54-----

43-51-

26-34---

-30-36

-19-25

-24-3226-3127-3528-35

-16-23

--

31-39--

28-3425-32

--

28-3430-35

-26-3223-27

-25-3127-3419-2519-2618-2530-38

-28-3525-30

-26-3324-31 28-34 21-28

-20-25 25-34

-22-2828-3525-3123-2915-2116-21≤ 12e

24-30-

19-2425-30



73


Organism Haemophilus influenzae Neisseria gonorrhoeae Streptococcus pneumoniae

Medium Haemophilus Test Medium GC agar base and 1% definedgrowth supplement. The use ofa cysteine-free growthsupplement is not required fordisk diffusion testing.

MHA supplemented with 5%defibrinated sheep blood

Inoculum Direct colony suspension Direct colony suspension Direct colony suspension

Incubation Characteristics 5% CO2; 16 to 18 hours; 35 °C 5% CO2; 20 to 24 hours; 35 °C 5% CO2; 20 to 24 hours; 35 °C

Disk Diffusion Testing Conditions for Clinical Isolates and Performance of Quality Control

NOTE: Information in boldface is considered tentative for one year.

Footnotes

a. ATCC is a registered trademark of American Type Culture Collection.

b. Despite the lack of reliable disk diffusion interpretive criteria for S. pneumoniae with certain β-lactams, Streptococcuspneumoniae ATCC® 49619 is the strain designated for quality control of all disk diffusion tests with all Streptococcus spp.

c. When testing Haemophilus on HTM, the acceptable limits for QC strain E. coli ATCC® 35218 are 17 to 22 mm for amoxicillin-clavulanic acid.

d. Some lots of Mueller-Hinton agar are deficient in calcium and give small zones.

e. Deterioration in oxacillin disk content is best assessed with QC organism Staphylococcus aureus ATCC® 25923, with anacceptable zone diameter of 18 to 24 mm.



ATCC® 49247a


ATCC® 49766

Neisseria gonorrhoeae ATCC® 49226


ATCC® 49619b

SparfloxacinSpectinomycinTelavancinTelithromycinTetracyclineTigecyclineTrimethoprim-sulfamethoxazoleTrospectomycinTrovafloxacinVancomycin

5 µg100 µg30 µµg15 µg30 µg15 µµg

1.25/23.75 µg30 µg10 µg30 µg

32-40--

17-2314-2223-3124-3222-2932-39

-

----------

43-5123-29

--

30-4230-40

-28-3542-55

-

21-27-

17-2427-3327-3123-2920-28

-25-3220-27

Tabl

e 3A

Fast

idio

us Q

ualit

y C

ontro

lM

2-D

isk

Diff

usio

n



Tabl

e 3B

QC

Tes

ting

Freq

uenc

yM

2-D

isk

Diff

usio

n

NOTE 1: Addition of any NEW antimicrobial agent requires 20 or 30 consecutive days of satisfactory testing (see M2-A8,Section 10.5) prior to use of this guide.

NOTE 2: QC can be performed prior to or concurrent with testing patient isolates. Patient results can be reported for that day ifquality control results are within the acceptable limits.

NOTE 3: Manufacturers of commercial or in-house prepared tests should follow their own internal procedures and applicableregulations.

NOTE 4: For troubleshooting out-of-range results, refer to M2-A8, Section 10.6.

NOTE 5: Broth, saline, and/or water used to prepare an inoculum does not require routine quality control.

FOOTNOTE

a. Does not eliminate the need for routine weekly or daily QC testing.

Number of Days of Consecutive QCTesting Requireda

Test Modification 1 5 20 or 30 CommentsDisksUse new shipment or lot number XUse new manufacturer XMedia (prepared agar plates)Use new shipment or lot number XUse new manufacturer XInoculum PreparationConvert inoculum preparation/standardization to use of a devicethat has its own QC protocol.

X Example:Convert from visual adjustmentof turbidity to use of aphotometric device for which aquality control procedure isprovided.

Convert inoculum preparation/standardization to a method that isdependent on user technique.

X Example:Convert from visual adjustmentof turbidity to another methodthat is not based on aphotometric device.

Measuring ZonesChange method of measuringzones.

X Example:Convert from manual zonemeasurements to automatedzone reader.

In addition, perform in-housevalidation studies.

Instrument/Software (e.g., automated zone reader)Software update that affects ASTresults

X Monitoring all drugs, not justthose implicated in softwaremodification

Repair of instrument that affectsAST results

X Depending on extent of repair(e.g., critical component such asthe photographic device),additional testing may beappropriate (e.g., five days).

Table 3B. Reference Guide to Quality Control Testing Frequency

This table summarizes the suggested frequency of testing CLSI/NCCLS-recommended ATCC qualitycontrol strains to be performed by the user of antimicrobial susceptibility tests (AST). It applies only toantimicrobial agents for which 20 or 30 consecutive test days of quality control testing producedsatisfactory results.


76

Tabl

e 4

Sugg

este

d Te

st Re

sult

Verif

icat

ion

and

Org

anism

Iden

tific

atio

nM

2-D

isk

Diff

usio

n


a When results listed in this category are observed on individual patient isolates, they should be verified by one or moreof the following:

1. Ensuring the unusual results are not due to transcription errors, contamination, or use of a defective panel,plate, or card.

2. Checking previous reports on the patient to determine if the isolate was encountered and verified earlier.3. Confirming the identification of the isolate.4. Repeating the susceptibility test to confirm results. Sometimes it is helpful to use an alternative test method

for the repeat test. 5. For isolates that show results other than susceptible for those antimicrobial agents for which only susceptible

interpretive criteria are provided in Tables 2A to 2I (listed with an “NS” above) and for staphylococci withvancomycin-intermediate or vancomycin-resistant results: 1) confirm the organism identification; 2) confirmthe antimicrobial susceptibility test results; 3) save the isolate; and 4) submit the isolate to a referencelaboratory that will test it by a CLSI/NCCLS reference dilution method.

b When results listed in this category are observed on individual patient isolates, the verification steps as outlined forCategory I should be considered if the resistance is uncommon in a given institution.

c For these antimicrobial agent/organism combinations, resistance has not been documented to date.d

When submitting reports to a public health laboratory, include antimicrobial susceptibility results forSalmonella spp. that are intermediate or resistant to 3rd-generation cephalosporins and/or intermediate orresistant to fluoroquinolone or resistant to nalidixic acid.

Table 4. Suggestions for Verification of Antimicrobial Susceptibility Test Results and Confirmationof Organism Identification

This table reflects the drugs listed for testing against the respective organisms in Tables 2A to 2I in M100and gives some examples to consider for verification protocols at a given institution. The list includesphenotypes that: 1) have never been documented; 2) are uncommon; and/or 3) represent results thatcould easily occur from technical errors and may have significant clinical consequences.

Organism or GroupCategory Ia

Phenotypes that have not beenreported, are uncommon, and/or

result from technical errors

Category IIb

Phenotypes that may be uncommon at agiven institution and/or result from

technical errors Gram-negative organismsEnterobacteriaceae (any) carbapenem - I or R amikacin - R

fluoroquinolone - R

Citrobacter freundii Enterobacter spp. Serratia marcescens

ampicillin, cefazolin, or cephalothin- S

Escherichia coli ESBL confirmed positiveKlebsiella spp. ampicillin - S ESBL confirmed positiveProteus vulgaris Providencia spp.

ampicillin - S

Salmonella spp. 3rd-generation cephalosporin - I or Rd

fluoroquinolone - I or R; or nalidixicacid - Rd

Pseudomonas aeruginosa concurrent gentamicin and tobramycinand amikacin - R

Stenotrophomonas maltophilia

carbapenem - S trimethoprim-sulfamethoxazole - R

Haemophilus influenzae aztreonam - NS carbapenem - NS3rd-generation cephalosporinc - NSfluoroquinolone - NS

ampicillin - R and β-lactamase-negativeamoxicillin-clavulanic acid - R

Neisseria gonorrhoeae 3rd-generation cephalosporin - R fluoroquinolone - RAny organism Resistant to all agents routinely

tested


77

Tabl

e 4

Sugg

este

d Te

st Re

sult

Verif

icat

ion

and

Org

anism

Iden

tific

atio

nM

2-D

isk

Diff

usio

n


Organism or Group

Category Ia



Category IIb

Phenotypes that may be uncommonat a given institution and/or result

from technical errors

Gram-positive organismsEnterococcus spp. daptomycin - NS vancomycin - REnterococcus faecalis ampicillin or penicillin - R

daptomycin - NSquinupristin-dalfopristin - Slinezolid - R

high-level aminoglycoside - R(particularly if isolate from sterile bodysite)

Enterococcus faecium daptomycin - NSlinezolid - R

high-level aminoglycoside - R(particularly if isolate from sterile bodysite)

quinupristin-dalfopristin - R

Staphylococcus aureus daptomycin - NSlinezolid - NS quinupristin-dalfopristin - I or Rvancomycin - I or R

oxacillin - R

Staphylococcus,coagulase-negative

daptomycin - NSlinezolid - NS vancomycin - I or R


fluoroquinolone - Rlinezolidc - NSvancomycinc - NS

penicillin - R3rd-generation cephalosporin - R

Streptococcus, beta group

ampicillin or penicillinc - NS3rd-generation cephalosporin - NSdaptomycin - NSlinezolid - NSvancomycinc - NS

Streptococcus, viridansgroup

daptomycin - NSlinezolid - NSvancomycin - NS

penicillin - I or R

Any organism Resistant to all agents routinely tested

a When results listed in this category are observed on individual patient isolates, they should be verified by one or moreof the following:




interpretive criteria are provided in Tables 2A to 2I (listed with an “NS” above) and for staphylococci withvancomycin-intermediate or vancomycin-resistant results: 1) confirm the organism identification; 2) confirmthe antimicrobial susceptibility test results; 3) save the isolate; and 4) submit the isolate to a referencelaboratory that will test it by a CLSI/NCCLS reference dilution method.

b When results listed in this category are observed on individual patient isolates, the verification steps as outlined forCategory I should be considered if the resistance is uncommon in a given institution.

c For these antimicrobial agent/organism combinations, resistance has not been documented to date.




Glossary I (Part 1). ββ-lactams: Class and Subclass Designation and Generic NameAntimicrobial Class Antimicrobial Subclass Agents Included; Generic Namespenicillins penicillina penicillin

aminopenicillina amoxicillin

ampicillin

ureidopencillina azlocillinmezlocillinpiperacillin

carboxypenicillina carbenicillinticarcillin

penicillinase-stable

penicillinsb

cloxacillindicloxacillinmethicillinnafcillinoxacillin

amidinopenicillin mecillinamβ-lactam/β-lactamaseinhibitor combinations

amoxicillin-clavulanic acidampicillin-sulbactampiperacillin-tazobactamticarcillin-clavulanic acid

cephems (parenteral) cephalosporin Ic,e cefazolin

cephalothincephapirincephradine

cephalosporin IIc,e cefamandole

cefonicidcefuroxime (sodium)

cephalosporin IIIc,e cefoperazone

cefotaximeceftazidimeceftizoximeceftriaxone

cephalosporin IVc,e cefepime cephamycind cefmetazole

cefotetancefoxitin

oxacephem moxalactamcephems (oral) cephalosporine cefaclor

cefadroxilcefdinircefditorencefetametcefiximecefpodoximecefprozilceftibutencefuroxime (axetil)cephalexincephradine

carbacephem loracarbefmonobactams aztreonamcarbapenems doripenem

ertapenemimipenemmeropenem

a Penicillinase-labile; hydrolyzed by staphylococcal penicillinase.

b Not hydrolyzed by staphylococcal penicillinase.c Cephalosporin I, II, III, and IV are sometimes referred to as 1st-, 2nd-, 3rd-, and 4th-generation cephalosporins, respectively.

Cephalosporin III and IV are also referred to as “extended-spectrum cephalosporins.” This does not imply activity against ESBL-producing gram-negativebacteria.

d Although often referred to as a 2nd-generation cephalosporin, cephamycins are not included with the other cephalosporins with regard to reporting of ESBL-producing strains.

e For all confirmed ESBL-producing strains, the test interpretation should be reported as resistant for this antimicrobial class or subclass.

Glo

ssar

y I



Glossary I (Part 2). Non-ββ-lactams: Class and Subclass Designation and Generic Name

Antimicrobial Class Antimicrobial Subclass Agents Included; Generic Namesaminocyclitols spectinomycin

trospectinomycinaminoglycosides amikacin

gentamicinkanamycinnetilmicinstreptomycintobramycin

ansamycins rifampinquinolones quinolone cinoxacin

garenoxacinnalidixic acid

fluoroquinolone ciprofloxacinclinafloxacinenoxacinfleroxacingatifloxacingemifloxacingrepafloxacinlevofloxacinlomefloxacinmoxifloxacinnorfloxacinofloxacinsparfloxacintrovafloxacin

folate pathway inhibitors sulfonamidestrimethoprimtrimethoprim-sulfamethoxazole

fosfomycins fosfomycinketolides telithromycinlincosamides clindamycinlipopeptides daptomycin

polymyxins colistin polymyxin B

macrolides azithromycinclarithromycindirithromycinerythromycin

nitrofurans nitrofurantoinnitroimidazoles metronidazoleoxazolidinones linezolidglycopeptides glycopeptide oritavancin

vancomycinlipoglycopeptide dalbavancin

teicoplanintelavancin

phenicols chloramphenicolstreptogramins quinupristin-dalfopristintetracyclines doxycycline

minocyclinetetracycline

glycylcycline tigecycline

Glo

ssar

y I



Glossary II. Abbreviations/Routes of Administration/Drug Class for Antimicrobial Agents Listedin M100-S15

Glo

ssar

y II

Antimicrobial Agent Agent Abbreviationa Routes of Administrationb Drug Class

PO IM IV

Amikacin AN, AK, Ak, AMI, AMK

X X aminoglycoside

Amoxicillin AMX, Amx, AMOX, AC

X penicillin

Amoxicillin-clavulanic acid AMC, Amc, A/C, AUG,

Aug, XL, AML

X β-lactam/β-lactamase inhibitor

Ampicillin AM, Am, AMP X X X penicillinAmpicillin-sulbactam SAM, A/S,

AMS, ABX β-lactam/β-lactamase

inhibitorAzithromycin AZM, Azi, AZI, AZ X X macrolideAzlocillin AZ, Az, AZL X X penicillinAztreonam ATM, AZT, Azt, AT, AZM X monobactam

Carbenicillin (indanyl salt)

Carbenicillin

CB, Cb, BAR X

X X

penicillin

Cefaclor CEC, CCL, Cfr, FAC, CF X cephem

Cefadroxil CFR, FAD X cephemCefamandole MA, CM, Cfm, FAM X X cephemCefazolin CZ, CFZ, Cfz, FAZ, KZ X X cephemCefdinir CDR, Cdn, DIN, CD, CFD X cephemCefditoren CDN X cephemCefepime FEP, Cpe, PM, CPM X X cephemCefetamet CAT, FET X cephemCefixime CFM, FIX, Cfe, IX X cephemCefmetazole CMZ, CMZS, CMT X X cephemCefonicid CID, Cfc, FON, CPO X X cephemCefoperazone CFP, Cfp, CPZ, PER, FOP,

CPX X cephem

Cefotaxime CTX, TAX, Cft, FOT, CT X X cephemCefotetan CTT, CTN, Ctn, CTE,

TANS, CNX X cephem

Cefoxitin FOX, CX, Cfx, FX X X cephemCefpodoxime CPD, Cpd, POD, PX X cephemCefprozil CPR, CPZ, FP X cephemCeftazidime CAZ, Caz, TAZ, TZ X X cephemCeftibuten CTB, TIB, CB X cephemCeftizoxime ZOX, CZX, CZ, Cz, CTZ,

TIZX X cephem

Ceftriaxone CRO, CTR, FRX, Cax, AXO, TX

X X cephem

Cefuroxime (axetil)

Cefuroxime (sodium)

CXM, CFX, ROX, Crm, FUR, XM

X

X X

cephem

Cephalexin CN, LEX, CFL X cephemCephalothin CF, Cf, CR, CL, CEP,

CE, KFX cephem



Glossary II. (Continued)

Glo

ssar

y II

Antimicrobial Agent Agent Abbreviationa

Routes of Administrationb

Drug Class

PO IM IVCephapirin CP, HAP X X cephemCephradine RAD, CH X cephemChloramphenicol C, CHL, CL X X phenicolCinoxacin CIN, Cn X quinoloneCiprofloxacin CIP, Cp, CI X X fluoroquinoloneClarithromycin CLR, CLM,

CLA, Cla, CHX macrolide

Clinafloxacin CFN, CLX, LF X X fluoroquinoloneClindamycin CC, CM, CD, Cd, CLI,

DAX X X lincosamide

Colistin CL, CS, CT X lipopeptideDalbavancin DAL X glycopeptideDaptomycin DAP X lipopeptideDicloxacillin DX, DIC X penicillinDirithromycin DTM, DT X macrolideDoripenem DOR X carbapenemErtapenem ETP X X carbapenemErythromycin E, ERY, EM X X macrolideFleroxacin FLE, Fle, FLX, FO X X fluoroquinoloneFosfomycin FOS, FF, FO, FM X fosfomycinGarenoxacin GRN X X quinoloneGatifloxacin GAT X X fluoroquinoloneGemifloxacin GEM X fluoroquinoloneGentamicinGentamicin synergy

GM, Gm, CN, GENGM500, HLG, Gms

X X aminoglycoside

Grepafloxacin GRX, Grx, GRE, GP X fluoroquinolone

Imipenem IPM, IMI, Imp, IP X carbapenemKanamycin K, KAN, HLK, KM X X aminoglycosideLevofloxacin LVX, Lvx,

LEV, LEVO, LEX X fluoroquinolone

Linezolid LNZ, LZ, LZD X X oxazolidinoneLomefloxacin LOM, Lmf X fluoroquinoloneLoracarbef LOR, Lor, LO X cephemMecillinam MEC X penicillinMeropenem MEM, Mer, MERO,

MRP, MPX carbapenem

Methicillin DP, MET, ME, SC X X penicillinMezlocillin MZ, Mz, MEZ X X penicillinMinocycline MI, MIN, Min, MN,

MNO, MC, MHX X tetracycline

Moxalactam MOX X X cephemMoxifloxacin MXF X X fluoroquinoloneNafcillin NF, NAF, Naf X X penicillinNalidixic acid NA, NAL X quinoloneNetilmicin NET, Nt, NC X X aminoglycosideNitrofurantoin F/M, FD, Fd, FT,

NIT, NI, FX nitrofurantoin

Norfloxacin NOR, Nxn, NX X fluoroquinoloneOfloxacin OFX, OFL, Ofl, OF X X X fluoroquinoloneOritavancin ORI X glycopeptideOxacillin OX, Ox, OXS, OXA X X X penicillin



Glossary II. (Continued)

Glo

ssar

y II

Antimicrobial Agent AgentAbbreviationa


Drug Class

PO IM IVPenicillin P, PEN, PV X X X penicillinPiperacillin PIP, PI, PP, Pi X X penicillin Piperacillin-tazobactam TZP, PTZ, P/T, PTc X β-lactam/β-lactamase

inhibitor combinationPolymyxin B PB X lipopeptideQuinupristin-dalfopristin SYN, Syn, QDA,

RPX streptogramin

Rifampin RA, RIF, Rif, RI,RD

X X ansamycin

Sparfloxacin SPX, Sfx, SPA, SO X fluoroquinolone

Spectinomycin SPT, SPE, SC X X aminocyclitolStreptomycin

Streptomycin synergy

S, STR, StS, SM,

ST2000, HLS

X X aminoglycoside

Sulfonamides SSS, S3 X X folate pathway antagonist(some PO only)

Teicoplanin TEC, TPN, Tei,TEI, TP, TPL

X X glycopeptide

Telavancin TLV X glycopeptideTelithromycin TEL X ketolideTetracycline TE, Te, TET, TC X X tetracyclineTicarcillin TIC, TC, TI, Ti X X penicillinTicarcillin-clavulanic acid TIM, Tim, T/C,

TCC, TLcX β-lactam/β-lactamase

inhibitorTigecycline TGC X glycylcyclineTobramycin NN, TM, TO, To,

TOBX X aminoglycoside

Trimethoprim TMP, T, TR, W X folate pathway inhibitorTrimethoprim-sulfamethoxazole

SXT, SxT, T/S, TS,COT

X X folate pathway inhibitor

Trospectinomycin X X aminocyclitolTrovafloxacin TVA, Tva, TRV, TV X X fluoroquinolone

Vancomycin VA, Va, VAN X X glycopeptide

a Abbreviations assigned to one or more diagnostic products in the U.S.b As available in the U.S.

PO per OS (oral)IM intramuscularIV intravenous



List of Identical Abbreviations Used for More Than One Antimicrobial Agent inU.S. Diagnostic Products

Agent Abbreviation Antimicrobial Agents for Which RespectiveAbbreviation is Used

AZM Azithromycin, AztreonamAZ Azithromycin, Azlocillin

CB, Cb Ceftibuten, CarbenicillinCFR, Cfr Cefaclor, Cefadroxil

CF, Cf Cefaclor, CephalothinCM Clindamycin, Cefamandole

CFM, Cfm Cefixime, CefamandoleCZ, Cz Ceftizoxime, CefazolinCD, Cd Clindamycin, Cefdinir

CPZ Cefprozil, CefoperazoneCP, Cp Cephapirin, Cefoperazone, CiprofloxacinCN, Cn Cephalexin, Cefotetan, Cinoxacin, Gentamicin

CFX, Cfx Cefoxitin, CefuroximeCL Cephalothin, ChloramphenicolCH Clarithromycin, CephradineDX Doxycycline, DicloxacillinFO Fleroxacin, FosfomycinSC Spectinomycin, MethicillinSO Sparfloxacin, OxacillinTC Tetracycline, Ticarcillin

Iden

tical

Abb

revi

atio

ns

for

Ant

imic

robi

al A

gent

s



Summary of Comments and Subcommittee Responses

M100-S14: Performance Standards for Antimicrobial Susceptibility Testing; Fourteenth InformationalSupplement (M2-Disk Diffusion)

1. Amoxicillin-sulbactam is marketed and prescribed in more than 20 countries all over the world. The breakpointscannot be extrapolated from the results of amoxicillin-clavulanate or ampicillin-sulbactam, even though crosssusceptibility among these drugs does exist. We feel that this point should be clarified in Clinical andLaboratory Standards Institute/NCCLS recommendations.

• Clinical and Laboratory Standards Institute is able to establish interpretive criteria only forantimicrobial agents which have been presented and discussed at CLSI meetings. If sufficient dataconforming to CLSI/NCCLS document M23—Development of In Vitro Susceptibility Testing Criteria andQuality Control Parameters for amoxicillin-sulbactam were presented to the subcommittee, we wouldconsider a request for interpretive criteria for that compound.

2. Sodium fosfomycin (not trometamol) is commonly used in Latin America for the treatment of severalinfections. Seven Latin American countries use cefoperazone-sulbactam for severe infections. No breakpointsare available for either compound.

• There are breakpoints in the current documents for Enterococcus faecalis and Escherichia coli for oralfosfomycin. If sufficient data conforming to CLSI/NCCLS document M23—Development of In VitroSusceptibility Testing Criteria and Quality Control Parameters for sodium fosfomycin and forcefoperazone-sulbactam were presented to the subcommittee, we would consider a request forinterpretive criteria for those compounds.

Table 2A

3. In South America, azithromycin (AZ) is at present largely used for the treatment of bacterial gastroenteritis dueto Salmonella spp. or Shigella spp. Breakpoints for the assay of AZ against these isolates should be included.

• If data conforming to CLSI/NCCLS document M23—Development of In Vitro Susceptibility TestingCriteria and Quality Control Parameters are presented to the subcommittee, we would consider addinginterpretive criteria for azithromycin for these organisms.

4. In South America, ESBLs are frequently found in Proteus mirabilis, Salmonella (non-typhi) and Shigella spp.Why does the Clinical and Laboratory Standards Institute consider only E. coli and Klebsiella spp. for ESBLdetection? Use of cefotaxime, ceftazidime, and cefepime should be encouraged for the phenotypic detection ofESBLs.

• We have recently carried out a study to determine the suitability of the ESBL screening and confirmationtests for P. mirabilis and that organism has been added to the ESBL table in Table 2A in M2 and M7 alongwith E. coli, K. pneumoniae, and K. oxytoca. Although the use of cefepime for characterizing ESBLs hasbeen described, criteria for the use of cefepime with and without clavulanate has not been studiedsufficiently to date to be included in the document. The same is true for Salmonella and Shigella spp.,which precludes adding them to the list at this time.

Table 2B

5. Why is only levofloxacin included as a new fluoroquinolone for Stenotrophomonas maltophilia testing by diskdiffusion? What about moxifloxacin and gatifloxacin?

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Clinical and Laboratory Standards Institute consensus procedures include an appeals process thatis described in detail in Section 8 of the Administrative Procedures. For further information,contact the Executive Offices or visit our website at www.clsi.org.



• In recent studies to develop disk diffusion criteria for S. maltophilia, only agents with clinical efficacynoted in the published literature were included. At this time, clinical data to support the use ofmoxifloxacin and/or gatifloxacin against S. maltophilia are limited or do not exist. If sufficient dataconforming to CLSI/NCCLS document M23—Development of In Vitro Susceptibility Testing Criteria andQuality Control Parameters for testing of other agents against S. maltophilia were presented to thesubcommittee, we would consider a request for interpretive criteria for those compounds.

6. Why should ceftazidime and not cefepime be tested by disk diffusion vs. Burkholderia cepacia?

• In recent studies to develop disk diffusion criteria for B. cepacia, only agents where clinical efficacy hadbeen suggested in the published literature were included. If sufficient data conforming to CLSI/NCCLSdocument M23—Development of In Vitro Susceptibility Testing Criteria and Quality Control Parametersfor testing of other agents against B. cepacia were presented to the subcommittee, we would consider arequest for interpretive criteria for those compounds.

Table 2C

7. We currently do not perform any definitive identification testing on any coagulase-negative staphylococci(CoNS). We do a rapid latex, and if negative, report as CoNS. In M100-S14, the text states that testing formecA or PBP 2a is to be performed on non-Staphylococcus epidermidis isolates, are you then saying that Imust now perform definitive identification for all coagulase-negative staphylococci?

• The Clinical and Laboratory Standards Institute does not require identification of coagulase-negativestaphylococci to the species level, with two exceptions: 1) laboratories should identify S. saprophyticusin urinary isolates for which susceptibility testing is not recommended; and 2) laboratories shouldidentify S. lugdunensis, an uncommon pathogen, but one that can cause endocarditis. For laboratoriesthat do not wish to identify all coagulase-negative staphylococci to species level, S. saprophyticus and S.lugdunensis can be easily identified using a few simple tests (Clinical Microbiology ProceduresHandbook, 2nd edition, 2004, ASM Press; Manual of Clinical Microbiology, 8th edition 2003, ASMPress). S. saprophyticus is novobiocin resistant at ≤≤16 mm on Mueller-Hinton agar. S. lugdunensis canbe identified using pyrrolidonyl arylamidase and ornithine decarboxylase. S. lugdunensis is stronglyPYR positive and ornithine decarboxylase positive. A simple scheme for identification of S. lugdunensishas also been proposed by Schnitzler, et al. (J Clin Microbiol, 36:812-13, 1998).

8. If we have a patient with pure culture of coagulase-negative staphylococci from a lower respiratory specimen,a wound, or a catheter tip, are you suggesting that because these are not sterile sites, we should not beperforming the mecA testing? Is this mecA test ONLY for sterile site specimens, or is it for serious infectionsand sites? You know that a terminology of “serious infection” falls into a gray zone.

• The definition of serious infection should be institution-specific. Laboratories, in consultation withinfectious disease clinicians, should decide which specimens warrant additional testing of CoNS formecA or PBP 2a. For example, isolates from endocarditis and osteomyelitis would fall into this category.

9. I have a question regarding the use of the cefoxitin disk to predict for oxacillin resistance in Staphylococcusspecies as outlined in M100-S14. The following two statements in the document are in themselves easilyunderstood.

M100-S14, page 104, Warning 2, states, “For oxacillin-resistant Staphylococcus aureus and coagulase-negative staphylococci, all penicillins, cephems, and other ß-lactams...may appear active in vitro but are noteffective clinically. Results for these drugs should be reported as resistant or should not be reported.”

M100-S14, page 105, comment 10, states, “For oxacillin-susceptible strains, results for parenteral and oralcephems, ß-lactam/ß-lactamase inhibitor combinations, and carbapenems, if tested, should be reportedaccording to the results generated using routine interpretative criteria.”

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It is when I attempt to combine the information that I am becoming confused.

Let’s say that I have a Staphylococcus species with MICs for oxacillin and cefazolin which interpret asresistant, but the cefoxitin disk diffusion interpretation is susceptible. Do I change the cephems, and other ß-lactams to susceptible as well, following the logic of page 104, warning 2, or do I leave the cephems and otherß-lactams as resistant in accordance with comment 10 on page 105?

• Testing of staphylococci against cefazolin and cefoxitin using an MIC method is not recommended.Determination of oxacillin susceptibility is best done with oxacillin when using an MIC method and bycefoxitin when doing disk diffusion. These phenotypic test methods correlate best with the presence orabsence of the mecA gene, which is associated with oxacillin resistance. Susceptibility to cefazolin andother cephems should be predicted using oxacillin when performing an MIC test or cefoxitin (foroxacillin) when performing disk diffusion.

10. If I were to not perform any definitive identification on coagulase-negative staphylococci isolates andperformed the mecA test, what are the implications if the isolate was truly a Staphylococcus epidermidis?

• Tests for mecA and the gene product PBP 2a are accurate and rapid methods for detecting oxacillinresistance in S. aureus and all coagulase-negative staphylococci including S. epidermidis.

11. In Table 2C (M7), comment 10, is this mecA testing for coagulase-negative staphylococci isolates only, or isit also for Staphylococcus aureus?

• See the response to question 10.

12. Why is CLSI moving to the cefoxitin disk screen test for oxacillin resistance detection in staphylococci? It isclear that there is better correlation between oxacillin resistance and mecA detection or the latex test for PBP2a. This information should be stated in the CLSI/NCCLS recommendations.

• For S. aureus and S. lugdunensis, the cefoxitin disk test is comparable to the oxacillin disk test forprediction of mecA-mediated resistance to oxacillin; however, the cefoxitin disk test is easier to read andtherefore it is the preferred method. For coagulase-negative staphylococci, oxacillin interpretive criteriacorrelate with the presence or absence of the gene encoding oxacillin resistance (mecA) in S. epidermidis;however, these interpretive criteria may overcall resistance for other coagulase-negative staphylococci(e.g., S. saprophyticus). For coagulase-negative staphylococci, the cefoxitin disk test has greaterspecificity than oxacillin and equal sensitivity, although it may miss some strains of mecA-positive S.simulans. It is true, however, that mecA detection and the latex test for PBP 2a are the most accuratepredictors of mecA-mediated resistance and these tests should be used when available and clinicallyrelevant. However, not all laboratories have the resources to perform these tests.

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For Use With M7-A6–MIC Testing M100-S15


Introduction to Tables 1 Through 1B and 2A Through 2L for Use With M7-A6—MIC Testing

I. Selecting Antimicrobial Agents for Testing and Reporting

A. Selection of the most appropriate antimicrobial agents to test and to report is a decision best madeby each clinical laboratory in consultation with the infectious disease practitioners and thepharmacy, as well as the pharmacy and therapeutics and infection control committees of themedical staff. The recommendations here for each organism group comprise agents of provenefficacy that show acceptable in vitro test performance. Considerations in the assignment of agentsto specific test/report groups include clinical efficacy, prevalence of resistance, minimizingemergence of resistance, cost, FDA indications, and current consensus recommendations for first-choice and alternative drugs, in addition to the specific issues described. Tests of selected agentsmay be useful for infection control purposes.

B. The listing of drugs together in a single box designates clusters of comparable agents that need notbe duplicated in testing, because interpretive results are usually similar and clinical efficacycomparable. In addition, an “or” designates a related group of agents that has an almost identicalspectrum of activity and interpretive results, and for which cross-resistance and susceptibility arenearly complete. Therefore, usually only one of the agents within each selection box (cluster orrelated group) need be selected for testing. Agents reported must be tested, unless reporting basedon testing another agent provides a more accurate result (e.g., susceptibility of staphylococci tocefazolin or cephalothin based on oxacillin testing), and they usually should match those includedin the hospital formulary; or else the report should include footnotes indicating the agents thatusually show comparable interpretive results. Unexpected results should be considered forreporting (e.g., resistance of Enterobacteriaceae to third-generation cephalosporins or imipenem).

On the following pages, you will find:

1. Tables 1 and 1A—Suggested groupings of U.S. FDA-approved antimicrobial agents thatshould be considered for routine testing and reporting by clinical microbiologylaboratories.

2. For each organism group, an additional table (Tables 2A through 2L) that contains:a. Recommended testing conditions.b. Minimal QC recommendations. (See also the M7-A6 text document, Section 12.)c. General comments for testing the organism group and specific comments for testing

particular drug/organism combinations.d. Suggested agents that should be considered for routine testing and reporting by

clinical microbiology laboratories as specified in Tables 1 and 1A (test/report groupsA, B, C, U; the latter for “urine”).

e. Additional drugs that have an approved indication for the respective organism group,but would generally not warrant routine testing by a clinical microbiology laboratoryin the United States (test/report group O for “other”; test/report group Inv. for“investigational” [not yet FDA approved]).

f. Minimal inhibitory concentration (MIC) interpretive standards.



C. Test/Report Groups

1. As listed in Tables 1 and 1A, agents in Group A are considered appropriate for inclusionin a routine, primary testing panel, as well as for routine reporting of results for thespecific organism groups.

2. Group B comprises agents that are important clinically, particularly for nosocomialinfections, and they may warrant primary testing. However, they may be reported onlyselectively, such as when the organism is resistant to agents of the same class, as in GroupA. Other indications for reporting the result might include a selected specimen source(e.g., a third-generation cephalosporin for enteric bacilli from cerebrospinal fluid [CSF]or trimethoprim-sulfamethoxazole for urinary tract isolates); a polymicrobial infection;infections involving multiple sites; on request in case of allergy, intolerance, or failure torespond to an agent in Group A; or for reporting to infection control as an epidemiologicaid.

3. Group C comprises alternative or supplemental antimicrobial agents that may requiretesting in those institutions that harbor endemic or epidemic strains resistant to several ofthe primary drugs (especially in the same class, e.g., β-lactams or aminoglycosides); fortreatment of patients allergic to primary drugs; for treatment of unusual organisms (e.g.,chloramphenicol for extraintestinal isolates of Salmonella spp. or vancomycin-resistantenterococci); or for reporting to infection control as an epidemiologic aid.

4. Group U (“urine”) lists certain antimicrobial agents (e.g., nitrofurantoin and certainquinolones) that are used only or primarily for treating urinary tract infections. Theseagents should not be routinely reported against pathogens recovered from other sites ofinfection. Other agents with broader indications may be included in Group U for specificurinary pathogens (e.g., P. aeruginosa).

5. Group O (“other”) includes agents that have a clinical indication for the organism groupbut are generally not candidates for routine testing and reporting in the United States.

6. Group Inv. (“investigational”) includes agents that are investigational for the organismgroup and have not yet been approved by the FDA.

D. Selective Reporting

Each laboratory should decide which agents in the tables to report routinely (Group A) and whichmight be reported only selectively (from Group B), in consultation with the infectious diseasepractitioners and the pharmacy, as well as the pharmacy and the therapeutics and infection controlcommittees of the medical staff of the hospital. Selective reporting should help improve theclinical relevance of test reports and help minimize the selection of multiresistant nosocomialstrains by overuse of broad-spectrum agents. Results for Group B agents not reported routinelyshould be available on request, or they may be reported for selected specimens. Unexpectedresistance, when confirmed, should be reported (e.g., resistance to a secondary agent butsusceptibility to a primary agent).



II. Reporting MIC Results

A. The MIC values determined as described in this document may be reported directly to cliniciansfor patient-care purposes. However, it is essential for an understanding of the data by all cliniciansthat an interpretive category result also be provided routinely. Recommended interpretivecategories for various MIC values are included in tables for each organism group and are basedon evaluation data as described in CLSI/NCCLS document M23—Development of In VitroSusceptibility Testing Criteria and Quality Control Parameters.

Recommended interpretive criteria are based on usual dosage regimens and routes ofadministration in the U.S.

1. Susceptible (S)

The “susceptible” category implies that an infection due to the strain may be appropriatelytreated with the dosage of antimicrobial agent recommended for that type of infection andinfecting species, unless otherwise contraindicated.

2. Intermediate (I)

The “intermediate” category includes isolates with antimicrobial agent MICs thatapproach usually attainable blood and tissue levels and for which response rates may belower than for susceptible isolates. The “intermediate” category implies clinicalapplicability in body sites where the drugs are physiologically concentrated (e.g.,quinolones and β-lactams in urine) or when a high dosage of a drug can be used (e.g., β-lactams). The “intermediate” category also includes a buffer zone which should preventsmall, uncontrolled technical factors from causing major discrepancies in interpretations,especially for drugs with narrow pharmacotoxicity margins.

3. Resistant (R)

Resistant strains are not inhibited by the usually achievable systemic concentrations of theagent with normal dosage schedules and/or fall in the range where specific microbialresistance mechanisms are likely (e.g., β-lactamases) and clinical efficacy has not beenreliable in treatment studies.

B. For organisms excluded from Tables 2A through 2L (e.g., Campylobacter spp., Corynebacteriumspp., Bacillus spp.) studies are not yet adequate to develop reproducible, definitive standards tointerpret results. These organisms may require different media, different atmospheres ofincubation, or show marked strain-to-strain variation in growth rate. For these microorganisms,consultation with an infectious disease specialist is recommended for guidance in determining theneed for susceptibility testing and in the interpretation of results. Published reports in the medicalliterature and current consensus recommendations for therapy of uncommon microorganisms mayobviate the need for testing. If necessary, a dilution method usually will be the most appropriatetesting method, and this may require submitting the organism to a reference laboratory.

If only “S” criteria are specified:For some organism/antimicrobial combinations, the absence of resistant strains precludesdefining any results categories other than “susceptible.” For strains yielding resultssuggestive of a “nonsusceptible” category, organism identification and antimicrobialsusceptibility test results should be confirmed. Subsequently, the isolates should be savedand submitted to a reference laboratory that will confirm results using a CLSI/NCCLSreference dilution method.



C. Policies regarding the generation of cumulative antibiograms should be developed in concert withthe infectious disease service, infection control personnel, and the pharmacy and therapeuticscommittee. Under most circumstances, the percentage of susceptible and intermediate resultsshould not be combined into the same statistics.

III. Therapy-Related Comments

Some of the comments in the tables relate to therapy concerns. These are denoted with an Rxsymbol. It may be appropriate to include some of these comments (or modification thereof) on thepatient report. An example would be inclusion of a comment on enterococcus susceptibilityreports from blood cultures that “enterococcal endocarditis requires combined therapy with high-dose penicillin or high-dose ampicillin or vancomycin or teicoplanin plus gentamicin orstreptomycin for bactericidal action.”

Antimicrobial dosage regimens often vary widely among practitioners and institutions. In somecases, the MIC interpretive criteria rely on pharmacokinetic-pharmacodynamic data using specifichuman dosage regimens. In cases where specific dosage regimens are important for properapplication of breakpoints, a therapy-related comment is included.

IV. Verification of Patient Results

Multiple test parameters are monitored by following the quality control recommendationsdescribed in this standard. However, acceptable results derived from testing quality control strainsdo not guarantee accurate results when testing patient isolates. It is important to review all of theresults obtained from all drugs tested on a patient’s isolate prior to reporting the results. Thisshould include but not be limited to ensuring that: 1) the antimicrobial susceptibility results areconsistent with the identification of the isolate; 2) the results from individual agents within aspecific drug class follow established hierarchy of activity rules (e.g., third-generation cephemsare more active than first- or second-generation cephems against Enterobacteriaceae); and 3) theisolate is susceptible to those agents for which resistance has not been documented (e.g.,vancomycin and Streptococcus spp.) and for which only “susceptible” interpretive criteria exist inM100.

Unusual or inconsistent results should be verified by checking for the following: 1) transcriptionerrors; 2) contamination of the test (recheck purity plates, etc.); 3) use of a defective panel, plate,or card (e.g., broken, underfilled); and 4) previous results on the patient (e.g., Did the patient havethe same isolate with an unusual antibiogram previously?) If a reason for the unusual orinconsistent result cannot be ascertained, a repeat of the susceptibility test or the identification orboth of these is in order. Sometimes it is helpful to use an alternative test method for the repeattest. A suggested list of results that may require verification is included in Table 8. Each laboratorymust develop its own policies for verification of unusual or inconsistent antimicrobialsusceptibility test results. This list should emphasize those results that are highly likely to impactpatient care.



V. Warning

Some of the comments in the tables relate to dangerously misleading results that can occur when certainantimicrobial agents are tested and reported as susceptible against specific organisms. These are denotedwith the word “Warning.”

“Warning”: The following antimicrobial agent/organism combinations may appear active in vitro butare not effective clinically and should not be reported as susceptible.

Location Organism Antimicrobial Agents That Must Not be Reported as Susceptible

Table 2A Salmonella spp., Shigella spp. 1st- and 2nd-generation cephalosporins, andaminoglycosides

Table 2C oxacillin-resistant Staphylococcusspp.

all penems, cephems, and other ß-lactamssuch as amoxicillin-clavulanic acid,piperacillin-tazobactam, and imipenem

Table 2D Enterococcus spp. aminoglycosides (except highconcentrations), cephalosporins,clindamycin, and trimethoprim-sulfamethoxazole

Table 2K (Table 2A) Yersinia pestis β-lactam antimicrobial agentsTable 7 Listeria spp. cephalosporins


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Table 1. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should BeConsidered for Routine Testing and Reporting on Nonfastidious Organisms by Clinical MicrobiologyLaboratories

GR

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AN

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Enterobacteriaceaeg Pseudomonas aeruginosaand Other Non-Enterobacteriaceaej

Staphylococcus spp. Enterococcus spp.n

Ampicillin g Ceftazidime Oxacillinl Penicillino or ampicillin

Cefazolina

Cephalothina

Gentamicin Penicillinl

Gentamicin Mezlocillin or ticarcillin

Piperacillin

Amikacin Amikacin

Azithromycind or

clarithromycind or

erythromycind

Daptomycins

Linezolid Quinupristin-

dalfopristinr

Amoxicillin-clavulanic acid orampicillin-sulbactam

Piperacillin-tazobactamTicarcillin-clavulanic acid

Cefepime Vancomycinp

Cefamandole orcefonicid orcefuroxime

CefoperazoneAztreonam

Clindamycind

DaptomycinCiprofloxacinLevofloxacin

Linezolid Telithromycind

Cefepime ImipenemMeropenem


CefmetazoleCefoperazoneg

CefotetanCefoxitin

Ticarcillin-clavulanic acidk Vancomycin

Tobramycin

Cefotaximeg, h, i orceftizoxime g, i orceftriaxoneg, h, i

Trimethoprim-sulfamethoxazolek

Ciprofloxacing orlevofloxacing

ErtapenemImipenem or

meropenemMezlocillin or

piperacillinTicarcillinTrimethoprim-sulfamethoxazoleg

AztreonamCeftazidime(Both are helpful indicators ofextended-spectrum β-lactamases.)i

Cefotaximek

orceftriaxone

k

Chloramphenicold Gentamicin (high-level resistance screen only)

Chloramphenicold, k

Netilmicin Ciprofloxacin orlevofloxacin orofloxacin

Gatifloxacin ormoxifloxacin

Streptomycin(high-level resistancescreen only)

Chloramphenicold, g Gentamicin Chloramphenicold

Erythromycind

Rifampinc

Tetracyclineb

(These agents may betested for VRE.)q

Kanamycin Quinupristin-dalfopristinmNetilmicin

Tetracyclineb Rifampinc

Tobramycin Tetracyclineb

GR

OU

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Carbenicillin Carbenicillin Lomefloxacin ornorfloxacin

CiprofloxacinLevofloxacinNorfloxacin

Cinoxacin Lomefloxacin or

norfloxacin orofloxacin

Gatifloxacin Ceftizoximek Nitrofurantoin

Loracarbef Lomefloxacin ornorfloxacin orofloxacin

NitrofurantoinNitrofurantoin Sulfisoxazole Sulfisoxazole Trimethoprim Trimethoprim Sulfisoxazole Tetracyclineb

Tetracyclineb,k

GR

OU

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For Use With M7-A6–MIC Testing M100-S15Table 1. (Continued)

GR

OU

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PRIM

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TEST

AN

D R

EPO

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Acinetobacter spp.j Burkholderia cepacia j Stenotrophomonas maltophilia j

Ceftazidime Trimethoprim-sulfamethoxazole


ImipenemMeropenem

AmikacinGentamicinTobramycin

Ceftazidime CeftazidimeChloramphenicol Chloramphenicol

Levofloxacin Levofloxacin

Ampicillin-sulbactamPiperacillin-tazobactamTicarcillin-clavulanate

Meropenem Minocycline Minocycline Ticarcillin-clavulanate

Ticarcillin-clavulanateCefepime

CefotaximeCeftriaxone

CiprofloxacinGatifloxacinLevofloxacin

DoxycyclineMinocyclineTetracycline

MezlocillinPiperacillinTicarcillin


Polymyxin B

GR

OU

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f

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REP

OR

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GR

OU

PU

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LFO

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E O

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NOTE 1: Selection of the most appropriate antimicrobial agents to test and to report is a decision made bestby each clinical laboratory in consultation with the infectious disease practitioners and the pharmacy,as well as the pharmacy and therapeutics and infection control committees of the medical staff. Thelists for each organism group comprise agents of proven efficacy that show acceptable in vitro testperformance. Considerations in the assignment of agents to Groups A, B, C, and U include clinicalefficacy, prevalence of resistance, minimizing emergence of resistance, cost, and current consensusrecommendations for first-choice and alternative drugs, in addition to the specific comments infootnotes “e” and “f.” Tests of selected agents may be useful for infection control purposes.

NOTE 2: The boxes in the table designate clusters of comparable agents that need not be duplicated in testing,because interpretive results are usually similar and clinical efficacy comparable. In addition, an “or”designates a related group of agents that has an almost identical spectrum of activity and interpretiveresults, and for which cross-resistance and susceptibility are nearly complete. Therefore, usually onlyone of the agents within each selection box (cluster or related group) need be selected for testing.Agents that are reported must be tested, unless reporting based on testing another agent provides amore accurate result (e.g., susceptibility of staphylococci to cefazolin or cephalothin based onoxacillin testing), and they usually should match those included in the hospital formulary; or else thereport should include footnotes indicating the agents that usually have comparable interpretiveresults. Finally, unexpected results should be considered for reporting (e.g., resistance ofEnterobacteriaceae to third-generation cephalosporins or imipenem).


FootnotesGeneral Comments

a. Cephalothin can be used to represent cephalothin, cephapirin, cephradine, cephalexin, cefaclor, andcefadroxil. Cefazolin, cefuroxime, cefpodoxime, cefprozil, and loracarbef (urinary isolates only) may be testedindividually, because some isolates may be susceptible to these agents when resistant to cephalothin.

b. Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline andminocycline. However, some organisms that are intermediate or resistant to tetracycline may be susceptibleto doxycycline or minocycline or both.

c. Rx: Rifampin should not be used alone for chemotherapy.

d. Not routinely reported on organisms isolated from the urinary tract.

e. Group B represents agents that may warrant primary testing but which should be reported only selectively,such as when the organism is resistant to agents of the same family in Group A. Other indications forreporting the result might include selected specimen sources (e.g., selected third-generation cephalosporinsfor isolates of enteric bacteria from CSF or trimethoprim-sulfamethoxazole for urinary tract isolates); statedallergy or intolerance, or failure to respond to an agent in Group A; polymicrobial infections; infectionsinvolving multiple sites with different microorganisms; or reports to infection control for epidemiologic aid.

“Warning”: The following antimicrobial agents should not be routinely reported forbacteria isolated from the CSF and which are included in this document. Theseantimicrobial agents are not the drugs of choice and may not be effective for treating CSFinfections caused by these organisms (i.e., the bacteria included in Tables 2A to 2J):




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f. Group C represents alternative or supplemental antimicrobial agents that may require testing in thoseinstitutions that harbor endemic or epidemic strains resistant to one or more of the primary drugs (especiallyin the same family, e.g., β-lactams or aminoglycosides), or for treatment of unusual organisms (e.g.,chloramphenicol for some Pseudomonas spp., and chloramphenicol, erythromycin, rifampin, and tetracyclinefor some vancomycin-resistant enterococci), or reporting to infection control as an epidemiologic aid.

Enterobacteriaceae

g. For fecal isolates of Salmonella and Shigella spp., only ampicillin, a fluoroquinolone, andtrimethoprim/sulfamethoxazole should be tested and reported routinely. In addition, chloramphenicol and athird-generation cephalosporin should be tested and reported for extraintestinal isolates of Salmonella spp.

h. Cefotaxime and ceftriaxone should be tested and reported on isolates from CSF in place of cephalothin andcefazolin.

i. Strains of Klebsiella spp. and E. coli that produce ESBLs may be clinically resistant to therapy with penicillins,cephalosporins, or aztreonam, despite apparent in vitro susceptibility to some of these agents. Some of thesestrains will show MICs above the normal susceptible population but below the standard breakpoints forcertain extended-spectrum cephalosporins or aztreonam; such strains may be screened for potential ESBLproduction by using the screening breakpoints listed at the end of Table 2A, Initial Screen Test. Other strainsmay test intermediate or resistant by standard breakpoints to one or more of these agents. In all strains withESBLs, the MICs for one or more of the extended-spectrum cephalosporins or aztreonam should decreasein the presence of clavulanic acid as described at the end of Table 2A, Phenotypic Confirmatory Test. For allconfirmed ESBL-producing strains, the test interpretation should be reported as resistant for all penicillins,cephalosporins, and aztreonam. (See Glossary I for specific agents included in the antimicrobial class,penicillins, and antimicrobial subclass, cephalosporins.)

Pseudomonas aeruginosa and Other Non-Enterobacteriaceae

j. Other non-Enterobacteriaceae include Pseudomonas spp., and other nonfastidious, glucose-nonfermenting,gram-negative bacilli except for Acinetobacter spp., Burkholderia cepacia, and Stenotrophomonasmaltophilia.

k. May be indicated for testing of some Pseudomonas spp. and other nonfastidious, glucose-nonfermenting, gram-negative bacilli.

Staphylococcus spp.

l. Penicillin-susceptible staphylococci are also susceptible to other penicillins, cephems, and carbapenemsapproved for use by the FDA for staphylococcal infections. Penicillin-resistant, oxacillin-susceptible strainsare resistant to penicillinase-labile penicillins but susceptible to other penicillinase-stable penicillins, β-lactam/β-lactamase inhibitor combinations, relevant cephems, and carbapenems. (See Glossary I for specificagents included in the antimicrobial class or antimicrobial subclass indicated). Oxacillin-resistantstaphylococci are resistant to all currently available β-lactam antibiotics. Thus, susceptibility or resistance toa wide array of β-lactam antibiotics may be deduced from testing only penicillin and oxacillin. Routine testingof other penicillins, β-lactamase inhibitor combinations, cephems, and carbapenems is not advised.

m. For reporting against methicillin-susceptible Staphylococcus aureus.

Enterococcus spp.

n. Warning: For Enterococcus spp., cephalosporins, aminoglycosides (except for high-level resistancescreening), clindamycin, and trimethoprim-sulfamethoxazole may appear active in vitro but are not effectiveclinically and should not be reported as susceptible.


96

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o. Penicillin susceptibility may be used to predict the susceptibility to ampicillin, amoxicillin, ampicillin-sulbactam, amoxicillin-clavulanic acid, piperacillin, and piperacillin-tazobactam for non-β-lactamase-producing enterococci. For blood and CSF isolates, a β-lactamase test is also recommended. Rx:Combination therapy of penicillin or ampicillin, plus an aminoglycoside, is usually indicated for seriousenterococcal infections, such as endocarditis.

p. Rx: Combination therapy with vancomycin plus an aminoglycoside is usually indicated for seriousenterococcal infections, such as endocarditis.

q. Because of limited alternatives, chloramphenicol, erythromycin, tetracycline (or doxycycline or minocycline),and rifampin may be tested for vancomycin-resistant enterococci, and consultation with an infectious diseasepractitioner is recommended.

r. For reporting against vancomycin-resistant Enterococcus faecium.

s. For reporting against vancomycin-susceptible Enterococcus faecalis.

98

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Table 1A. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should BeConsidered for Routine Testing and Reporting on Fastidious Organisms by Clinical MicrobiologyLaboratories

GR

OU

PA

PRIM

ARY

TEST

AN

D R

EPO

RT

Haemophilus spp.eNeisseria gonorrhoeaei Streptococcus pneumoniae

Streptococcus spp.Other ThanS. pneumoniae

Ampicilline, g Erythromycina Erythromycina, m, q

Penicillinj Penicillinl, n or ampicillinl, n



GR

OU

PB

b

PRIM

ARY

TEST

REP

OR

T SE

LEC

TIVE

LY

Ampicillin-sulbactamCefepime Cefotaximej or

ceftriaxonej

Chloramphenicolm

Cefuroxime sodium(parenteral)

Clindamycinm, q

Clindamycin

Cefotaximee orceftazidime orceftizoximee orceftriaxonee

Gatifloxacin GemifloxacinLevofloxacinMoxifloxacin OfloxacinSparfloxacin

Vancomycin

Chloramphenicole Meropenemj

Telithromycin

Meropeneme,h Tetracyclined

Vancomycinj

GR

OU

PC

C

SUPP

LEM

ENTA

LR

EPO

RT

SELE

CTI

VELY

Azithromycinf or clarithromycinf

Cefixime orcefotaxime orcefpodoxime orceftizoxime orceftriaxone

Amoxicillin or amoxicillin-clavulanic acid

Cefepime orcefotaxime orceftriaxoneAztreonam

Amoxicillin-clavulanic acidf

Cefaclorf or cefprozilf orloracarbeff

CefmetazoleCefotetanCefoxitinCefuroxime

Cefuroxime Daptomycinp

Cefdinirf orcefiximef orcefpodoximef

LevofloxacinOfloxacin

Cefonicid

Cefuroxime axetilf

(oral)Ciprofloxacin or

gatifloxacin orofloxacin

Chloramphenicol LinezolidQuinupristin-

dalfopristino

Ciprofloxacin or gatifloxacin or levofloxacin orlomefloxacin ormoxifloxacin orofloxacin orsparfloxacin

Gemifloxacin

Penicillin Ertapenem Imipenem

Linezolid

Ertapenem or imipenem

Spectinomycin Rifampink

Tetracyclined

Rifampin

Telithromycinf

Tetracyclined


99

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NOTE 1: Selection of the most appropriate antimicrobial agents to test and to report is a decision made bestby each clinical laboratory in consultation with the infectious disease practitioners and the pharmacy, aswell as the pharmacy and therapeutics and infection control committees of the medical staff. The lists foreach organism group comprise agents of proven efficacy that show acceptable in vitro test performance.Considerations in the assignment of agents to Groups A, B, and C include clinical efficacy, prevalence ofresistance, minimizing emergence of resistance, cost, and current consensus recommendations for first-choice and alternative drugs, in addition to the specific comments in footnotes “b” and “c.” Tests onselected agents may be useful for infection control purposes.

NOTE 2: The boxes in the table designate clusters of comparable agents that need not be duplicated intesting, because interpretive results are usually similar and clinical efficacy comparable. In addition, an“or” designates a related group of agents that has an almost identical spectrum of activity and interpretiveresults, and for which cross-resistance and susceptibility are nearly complete. Therefore, usually only oneof the agents within each selection box (cluster or related group) need be selected for testing. Agents thatare reported must be tested, unless reporting based on testing another agent provides a more accurateresult, and usually, they should match those included in the hospital formulary; or else the report shouldinclude footnotes indicating the agents that usually show comparable interpretive results. Lastly,unexpected results should be considered for reporting.

NOTE 3: Information in boldface type is considered tentative for one year. Footnotes

General Comments

a. Susceptibility and resistance to azithromycin, clarithromycin, and dirithromycin can be predicted bytesting erythromycin.

b. Group B represents agents that may warrant primary testing but which should be reported onlyselectively, such as when the organism is resistant to agents of the same class in Group A. Otherindications for reporting the result might include selected specimen sources (e.g., third-generationcephalosporin for isolates of Haemophilus influenzae from CSF); stated allergy or intolerance, or failureto respond to an agent in Group A; polymicrobial infections; infections involving multiple sites withdifferent microorganisms; or reports to infection control for epidemiologic aid.

c. Group C represents alternative or supplemental antimicrobial agents that may require testing in thoseinstitutions that harbor endemic or epidemic strains resistant to one or more of the primary drugs(especially in the same class, e.g., β-lactams), or for treatment of unusual organisms, or reporting toinfection control as an epidemiologic aid.

d. Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline andminocycline.

Haemophilus spp.

e. Only results of testing with ampicillin, one of the third-generation cephalosporins, chloramphenicol, andmeropenem should be reported routinely with CSF isolates of H. influenzae.

f. Amoxicillin-clavulanic acid, azithromycin, clarithromycin, cefaclor, cefprozil, loracarbef, cefdinir, cefixime,cefpodoxime, cefuroxime axetil, and telithromycin are oral agents that may be used as empiric therapyfor respiratory tract infections due to Haemophilus spp. The results of susceptibility tests with theseantimicrobial agents are often not useful for management of individual patients. However, susceptibilitytesting of Haemophilus spp. with these compounds may be appropriate for surveillance or epidemiologicstudies.

“Warning”: The following antimicrobial agents should not be routinely reported forbacteria isolated from the CSF and which are included in this document. Theseantimicrobial agents are not the drugs of choice and may not be effective for treating CSFinfections caused by these organisms (i.e., the bacteria included in Tables 2A to 2J):





100

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g. The results of ampicillin susceptibility tests should be used to predict the activity of amoxicillin. Themajority of isolates of H. influenzae that are resistant to ampicillin and amoxicillin produce a TEM-typeβ-lactamase. In most cases, a direct β-lactamase test can provide a rapid means of detecting ampicillinand amoxicillin resistance.

h. Clinical indications and relevant pathogens include bacterial meningitis and concurrent bacteremia inassociation with meningitis caused by H. influenzae (β-lactamase- and non-β-lactamase-producingstrains).


i. A β-lactamase test will detect one form of penicillin resistance in N. gonorrhoeae and also may be usedto provide epidemiologic information. Strains with chromosomally mediated resistance can be detectedonly by additional susceptibility testing, such as the disk diffusion method or the agar dilution MICmethod.


j. Only results of testing with penicillin, cefotaxime, ceftriaxone, meropenem, and vancomycin should bereported routinely for CSF isolates of S. pneumoniae.

k. Rx: Rifampin should not be used alone for chemotherapy.

Streptococcus spp.

l. Rx: Penicillin or ampicillin intermediate isolates may require combined therapy with an aminoglycosidefor bactericidal action.

m. Not routinely reported for organisms isolated from the urinary tract.

n. Susceptibility testing of penicillins and other β-lactams approved by FDA for treatment of Streptococcuspyogenes or Streptococcus agalactiae is not necessary for clinical purposes and need not be doneroutinely, since as with vancomycin, resistant strains have not been recognized. Interpretive criteria areprovided for pharmaceutical development, epidemiology, or monitoring for emerging resistance. Anystrains found to be intermediate or resistant should be referred to a reference laboratory forconfirmation.

o. Report against S. pyogenes.

p. For reporting against beta-hemolytic streptococci only.

q. Rx: Recommendations for intrapartum prophylaxis for Group B streptococci are penicillin orampicillin. While cefazolin is recommended for penicillin-allergic women at low risk foranaphylaxis, those at high risk for anaphylaxis may receive clindamycin or erythromycin. GroupB streptococci are susceptible to ampicillin, penicillin, and cefazolin, but may be resistant toclindamycin and/or erythromycin. When a group B streptococcus is isolated from a pregnantwoman with severe penicillin allergy (high risk for anaphylaxis), clindamycin and erythromycinshould be tested and reported.



Table 1B. Suggested Grouping of Antimicrobial Agents That Should Be Considered for Testingand Reporting on Potential Agents of Bioterrorism

Footnotes

General Comments

a. Organisms that are susceptible to penicillin are also considered susceptible to amoxicillin.

b. Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline. However,some organisms that are intermediate or resistant to tetracycline may be susceptible to doxycycline.

Bacillus anthracis Yersinia pestis Burkholderia mallei Burkholderiapseudomallei

Penicillina Gentamicin Ceftazidime Amoxicillin-clavulanicacid

Doxycycline or tetracyclineb

Streptomycin Doxycycline or tetracyclineb

Ceftazidime

Ciprofloxacin Doxycycline or tetracyclineb

Imipenem Doxycycline or tetracyclineb

Ciprofloxacin Imipenem

Chloramphenicol Trimethoprim-sulfamethoxazole


GR

OU

PA

PRIM

ARY

TEST

AN

D R

EPO

RT

Tabl

e 1B

Sugg

este

d Po

tent

ial A

gent

sof

Bio

terr

oris

m G

roup

ings

M7-

MIC

102

Tabl

e 2A

Ente

roba

cter

iace

aeM

7-M

IC


Test

ing

Con

ditio

ns

Med

ium

:B

roth

dilu

tion:

Cat

ion-

adju

sted

Mue

ller-

Hin

ton

brot

h

(CA

MH

B)

Aga

r dilu

tion:

Mue

ller H

into

n ag

ar (M

HA

)In

ocul

um:

Gro

wth

met

hod

or d

irect

col

ony

susp

ensi

on, e

quiv

alen

t to

a 0.

5 M

cFar

land

sta

ndar

dIn

cuba

tion:

35 °

C ±

2 de

gree

s; a

mbi

ent a

ir; 1

6 to

20

hour

s.

Tabl

e 2A

. M

IC In

terp

retiv

e St

anda

rds

(µµg/

mL)

for

Ente

roba

cter

iace

ae


Min

imal

QC

Rec

omm

enda

tions

(See

Tab

le 3

for a

ccep

tabl

e Q

C ra

nges

.)

Esch

eric

hia

coli

ATC

C®

259

22Es

cher

ichi

a co

liAT

CC

® 3

5218

(for

β-la

ctam

/β-la

ctam

ase

inhi

bito

rco

mbi

natio

ns)

Gen

eral

Com

men

ts(1

)Fo

rfe

cal

isol

ates

of

Salm

onel

laan

d Sh

igel

lasp

p.,

only

am

pici

llin,

a f

luor

oqui

nolo

ne,

and

trim

etho

prim

-sul

fam

etho

xazo

le s

houl

d be

tes

ted

and

repo

rted

rout

inel

y. I

n ad

ditio

n,ch

lora

mph

enic

ol a

nd a

third

-gen

erat

ion

ceph

alos

porin

sho

uld

be te

sted

and

repo

rted

for e

xtra

inte

stin

al is

olat

es o

f Sal

mon

ella

spp.

(2)

WA

RN

ING

: Fo

r Ye

rsin

ia p

estis

,stu

dies

hav

e de

mon

stra

ted

that

alth

ough

β-la

ctam

ant

imic

robi

al a

gent

s m

ay a

ppea

r ac

tive

in v

itro

they

lack

effi

cacy

in a

nim

al m

odel

s of

infe

ctio

n.Th

ese

antim

icro

bial

age

nts

shou

ld n

ot b

e re

porte

d as

sus

cept

ible

. Ref

er to

Tab

le 2

K fo

r tes

ting

of Y

. pes

tis.

NO

TE:

Info

rmat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

RPE

NIC

ILLI

NS

AA

mpi

cilli

n≤

816

≥32

(3) C

lass

repr

esen

tativ

e fo

r am

pici

llin

and

amox

icill

in.

B B B

Mez

loci

llin

orpi

pera

cilli

nTi

carc

illin

≤16

≤16

≤16

32-6

432

-64

32-6

4

≥12

8≥

128

≥12

8U

Car

beni

cilli

n≤

1632

≥64

U/In

vM

ecill

inam

≤8

16≥

32(4

) For

use

aga

inst

E. c

olif

or u

rinar

y tra

ct is

olat

es o

nly.

ββ -LA

CTA

M/ββ

-LA

CTA

MA

SE IN

HIB

ITO

R C

OM

BIN

ATIO

NS

B B B B

Am

oxic

illin

-cla

vula

nic

acid

or

ampi

cilli

n-su

lbac

tam

Pip

erac

illin

-tazo

bact

amTi

carc

illin

-cla

vula

nic

acid

≤8/

4≤

8/4

≤16

/4≤

16/2

16/8

16/8

32/4

-64/

432

/2-6

4/2

≥32

/16

≥32

/16

≥12

8/4

≥12

8/2

103

Tabl

e 2A

Ente

roba

cter

iace

aeM

7-M

IC


For Use With M7-A6–MIC Testing M100-S15Ta

ble

2A. (

Con

tinue

d)Te

st/R

epor

tG

roup

Ant

imic

robi

al A

gent

MIC

(µµg/

mL)

Inte

rpre

tive

Stan

dard

Com

men

ts

SI

RC

EPH

EMS

(PA

REN

TER

AL)

(In

clud

ing

ceph

alos

porin

s I,

II, I

II, a

nd I

V. P

leas

e re

fer

to G

loss

ary

I.)(5

)W

AR

NIN

G:

For

Salm

onel

lasp

p. a

nd S

hige

llasp

p.,

first

- an

d se

cond

-gen

erat

ion

ceph

alos

porin

s m

ay a

ppea

r act

ive

in v

itro

but a

re n

ot e

ffect

ive

clin

ical

ly a

nd s

houl

d no

tbe

repo

rted

as s

usce

ptib

le.

(6)

Stra

ins

of K

lebs

iella

spp

. an

d E.

col

ith

at p

rodu

ce e

xten

ded-

spec

trum

bet

a-la

ctam

ase

(ES

BLs

) m

ay

be

clin

ical

ly

resi

stan

t to

th

erap

y w

ith

peni

cilli

ns,

ceph

alos

porin

s, o

r azt

reon

am, d

espi

te a

ppar

ent i

n vi

trosu

scep

tibili

ty to

som

e of

thes

eag

ents

. Som

e of

thes

e st

rain

s w

ill s

how

MIC

s ab

ove

the

norm

al s

usce

ptib

le p

opul

atio

nbu

t be

low

the

sta

ndar

d br

eakp

oint

s fo

r ce

rtain

ext

ende

d-sp

ectru

m c

epha

losp

orin

s or

aztre

onam

. S

uch

stra

ins

shou

ld b

e sc

reen

ed fo

r pot

entia

l ES

BL

prod

uctio

n by

usi

ng th

eE

SB

Lsc

reen

ing

brea

kpoi

nts

liste

d at

the

end

of th

is ta

ble

befo

re r

epor

ting

resu

lts fo

rpe

nici

llins

, ex

tend

ed-s

pect

rum

cep

halo

spor

ins,

or

aztre

onam

. O

ther

stra

ins

may

tes

tin

term

edia

te o

r res

ista

nt b

y st

anda

rd b

reak

poin

ts to

one

or m

ore

of th

ese

agen

ts. I

n al

lst

rain

s w

ith E

SB

Ls, t

he M

ICs

for o

ne o

r mor

e of

the

exte

nded

-spe

ctru

m c

epha

losp

orin

sor

azt

reon

am s

houl

d de

crea

se i

n th

e pr

esen

ce o

f cl

avul

anic

aci

d as

det

erm

ined

in

phen

otyp

ic c

onfir

mat

ory

test

ing.

For

all

conf

irmed

ES

BL-

prod

ucin

g st

rain

s, t

he t

est

inte

rpre

tatio

n sh

ould

be

repo

rted

as r

esis

tant

for

all

peni

cilli

ns,

ceph

alos

porin

s, a

ndaz

treon

am.

(See

tab

le l

ocat

ed a

t th

e en

d of

thi

s ta

ble

for

ES

BL

scre

enin

g an

dco

nfirm

ator

y te

sts.

R

efer

to

th

e gl

ossa

ry

for

defin

ition

s of

pe

nici

llins

an

dce

phal

ospo

rins.

) Th

e de

cisi

on t

o pe

rform

ES

BL

scre

enin

g te

sts

on a

ll ur

ine

isol

ates

shou

ld b

e m

ade

on a

n in

stitu

tiona

l bas

is, c

onsi

derin

g pr

eval

ence

, the

rapy

, and

infe

ctio

nco

ntro

l iss

ues.

(7)

R

outin

e sc

reen

ing

of

Prot

eus

mira

bilis

for

ESB

Lpr

oduc

tion

is

not

reco

mm

ende

d. H

owev

er, w

hen

it is

dee

med

clin

ical

ly re

leva

nt (e

.g.,

a ba

cter

emic

isol

ate)

the

ESB

Lsc

reen

tes

ting

MIC

bre

akpo

ints

, ce

ftazi

dim

e (M

IC ≥≥

2 µµ

g/m

L),

cefo

taxi

me

(MIC

≥≥ 2

µµg/

mL)

, or c

efpo

doxi

me

(MIC

≥≥ 2

µµg/

mL

rath

er th

an ≥≥

8 µµ

g/m

L)w

ill i

dent

ify p

resu

mpt

ive

ESB

Lpr

oduc

tion.

The

phe

noty

pic

conf

irmat

ory

test

usin

g ce

ftazi

dim

e an

d ce

fota

xim

e al

one

and

in c

ombi

natio

n w

ith c

lavu

lani

c ac

idca

n co

nfirm

ES

BL-

prod

ucin

g st

rain

s.

For

all

conf

irmed

ES

BL-

prod

ucin

g P.

mira

bilis

, the

test

inte

rpre

tatio

n sh

ould

be

repo

rted

as

resi

stan

t for

all

peni

cilli

ns,

ceph

alos

porin

s, a

nd a

ztre

onam

.

(8)

Ente

roba

cter

, C

itrob

acte

r, an

d Se

rratia

spp.

may

dev

elop

res

ista

nce

durin

gpr

olon

ged

ther

apy

with

thi

rd-g

ener

atio

n ce

phal

ospo

rins.

The

refo

re,

isol

ates

tha

t ar

ein

itial

ly s

usce

ptib

le m

ay b

ecom

e re

sist

ant

with

in t

hree

to

four

day

s af

ter

initi

atio

n of

ther

apy.

Tes

ting

of re

peat

isol

ates

may

be

war

rant

ed.

A AC

efaz

olin

C

epha

loth

in≤

8≤

816 16

≥32

≥32

(9)

Cep

halo

thin

can

be

used

to p

redi

ct a

ctiv

ity o

f cep

halo

thin

, cep

hapi

rin, c

ephr

adin

e,ce

phal

exin

, cef

aclo

r, an

d ce

fadr

oxil.

Cef

azol

in, c

efur

oxim

e, c

efpo

doxi

me,

cef

proz

il, a

ndlo

raca

rbef

(urin

ary

isol

ates

onl

y) m

ay b

e te

sted

indi

vidu

ally,

bec

ause

som

e is

olat

es m

aybe

sus

cept

ible

to th

ese

agen

ts w

hen

resi

stan

t to

ceph

alot

hin.

B B B

Cef

aman

dole

or

cefo

nici

d or

cefu

roxi

me

sodi

um (p

aren

tera

l)

≤8

≤8

≤8

16 16 16

≥32

≥32

≥32

BC

efep

ime

≤8

16≥

32B B B B

Cef

met

azol

e C

efop

eraz

one

C

efot

etan

C

efox

itin

≤16

≤16

≤16

≤8

32 32 32 16

≥64

≥64

≥64

≥32

104

Tabl

e 2A

Ente

roba

cter

iace

aeM

7-M

IC



Tabl

e 2A

. (C

ontin

ued)

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

RC

EPH

EMS

(PA

REN

TER

AL)

(Con

tinue

d)B B B

Cef

otax

ime

orce

ftizo

xim

e or

ceftr

iaxo

ne

≤8

≤8

≤8

16-3

216

-32

16-3

2

≥64

≥64

≥64

(10)

Cef

otax

ime

and

ceftr

iaxo

ne s

houl

d be

test

ed a

nd re

porte

d on

isol

ates

from

CS

F in

pla

ce o

f cep

halo

thin

and

cef

azol

in.

See

com

men

t (6)

.C

Cef

tazi

dim

e≤

8 16

≥32

See

com

men

t (6)

.O

Mox

alac

tam

≤

8 16

-32

≥64

CEP

HEM

S (O

RA

L)B

Cef

urox

ime

axet

il (o

ral)

≤4

8-16

≥32

ULo

raca

rbef

≤8

16≥

32O

Cef

aclo

r≤

816

≥32

OC

efdi

nir

≤1

2≥

4O

Cef

ixim

e ≤

12

≥4

OC

efpo

doxi

me

≤2

4≥

8S

ee c

omm

ent (

6).

OC

efpr

ozil

≤8

16≥

32

Inv.

Cef

etam

et≤

48

≥16

Inv.

Cef

tibut

en≤

816

≥32

(11)

Ind

icat

ed fo

r urin

e is

olat

es o

nly.

CA

RB

APE

NEM

SB B B

Erta

pene

m

Imip

enem

or

mer

open

em

≤2

≤4

≤4

4 8 8

≥8

≥16

≥16

MO

NO

BA

CTA

MS

CA

ztre

onam

≤8

16≥

32S

ee c

omm

ent (

6).

AM

INO

GLY

CO

SID

ES(1

2) W

AR

NIN

G:F

or S

alm

onel

lasp

p. a

nd S

hige

llasp

p., a

min

ogly

cosi

des

may

appe

ar a

ctiv

e in

vitr

obu

t are

not

effe

ctiv

e cl

inic

ally,

and

isol

ates

sho

uld

not b

ere

porte

d as

sus

cept

ible

.A

Gen

tam

icin

≤4

8≥

16B

Am

ikac

in≤

1632

≥64

CK

anam

ycin

≤16

32≥

64C

Net

ilmic

in≤

816

≥32

CTo

bram

ycin

≤4

8≥

16TE

TRA

CYC

LIN

ESC

Tetra

cycl

ine

≤4

8≥

16(1

3)

Org

anis

ms

that

are

sus

cept

ible

to

tetra

cycl

ine

are

also

con

side

red

susc

eptib

le t

o do

xycy

clin

e an

d m

inoc

yclin

e.

How

ever

, so

me

orga

nism

s th

atar

e in

term

edia

te o

r res

ista

nt to

tetra

cycl

ine

may

be

susc

eptib

le to

dox

ycyc

line

or m

inoc

yclin

e or

bot

h.O

Dox

ycyc

line

≤4

8≥

16O

Min

ocyc

line

≤4

8≥

16

105

Tabl

e 2A

Ente

roba

cter

iace

aeM

7-M

IC



Tabl

e 2A

. (C

ontin

ued)

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rd

Com

men

ts

SI

RFL

UO

RO

QU

INO

LON

ES(1

4)

Fluo

roqu

inol

one-

susc

eptib

le s

train

s of

Sal

mon

ella

that

tes

t re

sist

ant

tona

lidix

ic a

cid

may

be

asso

ciat

ed w

ith c

linic

al f

ailu

re o

r de

laye

d re

spon

se in

fluor

oqui

nolo

ne-tr

eate

d pa

tient

s w

ith

extra

inte

stin

al

salm

onel

losi

s.E

xtra

inte

stin

al is

olat

es o

f Sa

lmon

ella

shou

ld a

lso

be t

este

d fo

r re

sist

ance

to

nalid

ixic

ac

id.

For

isol

ates

th

at

test

su

scep

tible

to

flu

oroq

uino

lone

s an

dre

sist

ant t

o na

lidix

ic a

cid,

the

phys

icia

n sh

ould

be

info

rmed

that

the

isol

ate

may

not

be

erad

icat

ed

by

fluor

oqui

nolo

ne

treat

men

t. A

cons

ulta

tion

with

an

infe

ctio

us d

isea

se p

ract

ition

er is

reco

mm

ende

d.B

Cip

roflo

xaci

n or

levo

floxa

cin

≤1

≤2

2 4≥

4≥

8U

Gat

iflox

acin

≤2

4≥

8B

Gem

iflox

acin

≤0.

250.

5≥

1(1

5) F

DA

appr

oved

for K

lebs

iella

pne

umon

iae

U U U

Lom

eflo

xaci

n or

norfl

oxac

in o

rof

loxa

cin

≤2

≤4

≤2

4 8 4

≥8

≥16

≥8

OE

noxa

cin

≤2

4≥

8O

Gre

paflo

xaci

n≤

1 2

≥4

Inv.

Fler

oxac

in≤

24

≥8

QU

INO

LON

ESU

Cin

oxac

in≤

1632

≥64

O

Nal

idix

ic a

cid

≤16

–≥

32S

ee c

omm

ent (

11).

(16)

In

addi

tion

to te

stin

g ur

ine

isol

ates

, nal

idix

ic a

cid

may

be

used

to te

st fo

rre

duce

d flu

oroq

uino

lone

su

scep

tibili

ty

in

isol

ates

fro

m

patie

nts

with

extra

inte

stin

al S

alm

onel

lain

fect

ions

. See

com

men

t (14

).FO

LATE

PAT

HW

AYIN

HIB

ITO

RS

BTr

imet

hopr

im-s

ulfa

met

hoxa

zole

≤2/

38–

≥4/

76U

Sul

fona

mid

es≤

256

–

≥51

2(1

7) S

ulfis

oxaz

ole

can

be u

sed

to re

pres

ent a

ny o

f the

cur

rent

ly a

vaila

ble

sulfo

nam

ide

prep

arat

ions

.U

Trim

etho

prim

≤8

–≥

16PH

ENIC

OLS

CC

hlor

amph

enic

ol≤

816

≥32

(18)

N

ot ro

utin

ely

repo

rted

agai

nst o

rgan

ism

s is

olat

ed fr

om th

e ur

inar

y tra

ct.

FOSF

OM

YCIN

SU

Fosf

omyc

in≤

6412

8≥

256

(19)

Fo

r use

with

E. c

olio

nly.

The

app

rove

d M

IC s

usce

ptib

ility

test

ing

met

hod

is a

gar d

ilutio

n. A

gar m

edia

sho

uld

be s

uppl

emen

ted

with

25

µg/m

Lof

glu

cose

-6-

phos

phat

e. B

roth

dilu

tion

shou

ld n

ot b

e pe

rform

ed.

NIT

RO

FUR

AN

TOIN

SU

Nitr

ofur

anto

in≤

3264

≥12

8

106

Tabl

e 2A

Ente

roba

cter

iace

aeM

7-M

IC



Table 2A. (Continued)Screening and Confirmatory Tests for ESBLs in Klebsiella pneumoniae, K. oxytoca, Escherichiacoli, and Proteus mirabilis

a

Method Initial Screen Test Phenotypic Confirmatory TestMedium CAMHB CAMHBAntimicrobialConcentration

cefpodoxime 4 µg/mL orceftazidime 1 µg/mL oraztreonam 1 µg/mL orcefotaxime 1 µg/mL orceftriaxone 1 µg/mL

(The use of more than one antimicrobialagent for screening will improve thesensitivity of detection.)

ceftazidime 0.25-128 µg/mLceftazidime-clavulanic acid 0.25/4-128/4 µg/mLandcefotaxime 0.25-64 µg/mLcefotaxime-clavulanic acid 0.25/4-64/4 µg/mL

(Confirmatory testing requires use of bothcefotaxime and ceftazidime, alone and incombination with clavulanic acid.)

InoculumStandard broth dilution

recommendationsStandard broth dilution

recommendationsIncubationConditionsIncubation LengthResults Growth = may indicate ESBL

production (i.e., MIC ≥ 2 µg/mLfor ceftazidime, aztreonam, cefotaxime,or ceftriaxone; or MIC≥ 8 µg/mL for cefpodoxime)

A ≥ 3 twofold concentration decrease in an MIC foreither antimicrobial agent tested in combination withclavulanic acid versus its MIC when tested alone =ESBL (e.g., ceftazidime MIC= 8 µg/mL; ceftazidime-clavulanic acid MIC = 1 µg/mL).

QCRecommendations

When testing ESBL-screeningantimicrobial agents, K. pneumoniaeATCC® 700603 is provided for qualityassessment (e.g., training,competency or test evaluation).Either strain, K. pneumoniae ATCC®

700603 or E. coli ATCC® 25922, maythen be used for routine QC (e.g.,weekly or daily).

E. coli ATCC® 25922 = No growth(also refer to control limits listed in M7Table 3)

Klebsiella pneumoniae ATCC® 700603= Growth:

cefpodoxime MIC ≥ 8 µg/mLceftazidime MIC ≥ 2 µg/mLaztreonam MIC ≥ 2 µg/mLcefotaxime MIC ≥ 2 µg/mLceftriaxone MIC ≥ 2 µg/mL

When performing the ESBL confirmatory tests,K. pneumoniae ATCC® 700603 and E. coliATCC® 25922 should be tested routinely (e.g.,weekly or daily).

E. coli ATCC® 25922: <3 twofold concentrationdecrease in an MIC for an antimicrobial agenttested in combination with clavulanic acidversus its MIC when tested alone.

K. pneumoniae ATCC® 700603: ≥ 3 twofoldconcentration decrease in an MIC for anantimicrobial agent tested in combination withclavulanic acid versus its MIC when tested alone.

FOOTNOTE

a. Routine screening of Proteus mirabilis for ESBL production is not recommended. However, when it isdeemed clinically relevant (e.g., a bacteremic isolate) the ESBL screen testing MIC breakpoints, ceftazidime(MIC ≥≥ 2 µµg/mL), cefotaxime (MIC ≥≥ 2 µµg/mL ), or cefpodoxime (MIC ≥≥ 2 µµg/mL rather than ≥≥ 8 µµg/mL) willidentify presumptive ESBL production. The phenotypic confirmatory test using ceftazidime and cefotaximealone and in combination with clavulanic acid can confirm ESBL-producing strains. For all confirmed ESBL-producing P. mirabilis, the test interpretation should be reported as resistant for all penicillins,cephalosporins, and aztreonam.

Tabl

e 2B

Non

-Ent

erob

acte

riace

aeM

7-M

IC

Gen

eral

Com

men

ts

(1)

Non

-Ent

erob

acte

riace

ae in

clud

e Ac

inet

obac

ter

spp.

, Ste

notro

phom

onas

mal

toph

ilia, P

seud

omon

assp

p., a

nd o

ther

non

fast

idio

us, g

luco

se-n

onfe

rmen

ting,

gram

-neg

ativ

e ba

cilli

. Ref

er to

Tab

le 2

K fo

r te

stin

g of

Bur

khol

deria

mal

lei a

nd B

. pse

udom

alle

i.

(2)

The

susc

eptib

ility

of P

. aer

ugin

osa

isol

ated

from

pat

ient

s w

ith c

ystic

fibr

osis

can

be

relia

bly

dete

rmin

ed b

y th

e re

fere

nce

agar

dilu

tion

or fr

ozen

ref

eren

cebr

oth

mic

rodi

lutio

n m

etho

ds, b

ut m

ay re

quire

ext

ende

d in

cuba

tion

up to

24

hour

s be

fore

repo

rting

as

susc

eptib

le.

(3)

P. a

erug

inos

am

ay d

evel

op r

esis

tanc

e du

ring

prol

onge

d th

erap

y w

ith a

ll an

tibio

tics.

The

refo

re, i

sola

tes

that

are

initi

ally

sus

cept

ible

may

bec

ome

resi

stan

tw

ithin

thre

e to

four

day

s af

ter i

nitia

tion

of th

erap

y. T

estin

g of

repe

at is

olat

es m

ay b

e w

arra

nted

.

(4)

Rx:

P. a

erug

inos

ain

fect

ions

in g

ranu

locy

tope

nic

patie

nts

and

serio

us in

fect

ions

in o

ther

pat

ient

s sh

ould

be

treat

ed w

ith m

axim

um d

oses

of t

he s

elec

ted

antip

seud

omon

al p

enic

illin

(car

boxy

peni

cilli

n or

ure

idop

enic

illin

) or c

efta

zidi

me

in c

ombi

natio

n w

ith a

n am

inog

lyco

side

.

NO

TE:

Info

rmat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.



Min

imal

QC

Rec

omm

enda

tions

(See

Tab

le 3

for A

ccep

tabl

e Q

C R

ange

s.)

Pseu

dom

onas

aer

ugin

osa

ATC

C®

2785

3Es

cher

ichi

a co

liAT

CC

®25

922

Esch

eric

hia

coli

ATC

C®

352

18 (f

or β

-lact

am/β

-lact

amas

e in

hibi

tor

com

bina

tions

)

Test

ing

Con

ditio

ns

Med

ium

:

Bro

th d

ilutio

n: C

atio

n-ad

just

ed M

uelle

r-H

into

n br

oth

(CA

MH

B)

Aga

r dilu

tion:

Mue

ller-

Hin

ton

agar

(MH

A)

Inoc

ulum

:G

row

th m

etho

d or

dire

ct c

olon

y su

spen

sion

, equ

ival

ent t

o a

0.5

McF

arla

nd s

tand

ard

Incu

batio

n:35

°C

±2

degr

ees;

am

bien

t air;

16

to 2

0 ho

urs

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

RPE

NIC

ILLI

NS

A A A

Mez

loci

llin

or

ticar

cilli

n

Pip

erac

illin

≤64

≤16

≤64

≤16

≤64

≤16

-32

-64

-32

-64

-32

-64

≥12

8≥

128

≥12

8≥

128

≥12

8≥

128

For P

. aer

ugin

osa

only

For a

ll ot

her n

on-E

nter

obac

teria

ceae

For P

. aer

ugin

osa

only

For a

ll ot

her n

on-E

nter

obac

teria

ceae

For P

. aer

ugin

osa

only

For a

ll ot

her n

on-E

nter

obac

teria

ceae

UC

arbe

nici

llin

≤12

8≤

1625

632

≥

512

≥64

For P

. aer

ugin

osa

only

For a

ll ot

her n

on-E

nter

obac

teria

ceae

OA

zloc

illin

≤64

- ≥

128

For P

. aer

ugin

osa

only

ββ -LA

CTA

M/ββ

-LA

CTA

MA

SE IN

HIB

ITO

R C

OM

BIN

ATIO

NS

BTi

carc

illin

-cla

vula

nic

acid

≤16

/232

/2-6

4/2

≥12

8/2

For n

on-E

nter

obac

teria

ceae

oth

er th

an P

. aer

ugin

osa

(5) M

ay b

e in

dica

ted

for p

rimar

y te

stin

g of

som

e Ps

eudo

mon

assp

p. (o

ther

than

P. a

erug

inos

a), S

. mal

toph

ilia, a

nd A

cine

toba

cter

spp.

OTi

carc

illin

-cla

vula

nic

acid

≤64

/2-

≥12

8/2

For P

. aer

ugin

osa

only

OA

mpi

cilli

n-su

lbac

tam

≤8/

416

/8≥

32/1

6(6

) M

ay b

e re

porte

d fo

r Aci

neto

bact

ersp

p. re

sist

ant t

o ot

her a

gent

sO

Pip

erac

illin

-tazo

bact

am≤

64/4

≤16

/4-

32/4

-64/

4≥

128/

4≥

128/

4Fo

r P. a

erug

inos

aon

lyFo

r all

othe

r non

-Ent

erob

acte

riace

ae

Tabl

e 2B

. M

IC In

terp

retiv

e St

anda

rds

(µµg/

mL)

for

Pseu

dom

onas

aer

ugin

osa

and

Oth

er N

on-E

nter

obac

teria

ceae

109

Tabl

e 2B

Non

-Ent

erob

acte

riace

aeM

7-M

IC



Tabl

e 2B

. (C

ontin

ued)

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

RC

EPH

EMS

(PA

REN

TER

AL)

(Inc

ludi

ng c

epha

losp

orin

s I,

II, II

I, an

d IV

. Ple

ase

refe

r to

Glo

ssar

y I.)

AC

efta

zidi

me

≤8

16≥

32B

Cef

epim

e≤

816

≥32

BC

efop

eraz

one

≤16

32≥

64C C

Cef

otax

ime

orce

ftria

xone

≤8

≤8

16-3

216

-32

≥64

≥64

UC

eftiz

oxim

e≤

816

-32

≥64

OM

oxal

acta

m≤

816

-32

≥64

(7)

May

be

indi

cate

d fo

r prim

ary

test

ing

of S

. mal

toph

ilia.

CA

RB

APE

NEM

SB

Imip

enem

≤4

8≥

16B

Mer

open

em≤

48

≥16

LIPO

PEPT

IDES

CPo

lym

yxin

B≤≤

2-

≥≥4

(8)

Poly

myx

in B

MIC

res

ult c

an p

redi

ct c

olis

tin M

IC.

MO

NO

BA

CTA

MS

BA

ztre

onam

≤8

16≥

32A

MIN

OG

LYC

OSI

DES

AG

enta

mic

in≤

48

≥16

BA

mik

acin

≤16

32≥

64B

Tobr

amyc

in≤

48

≥16

CN

etilm

icin

≤8

16≥

32TE

TRA

CYC

LIN

ES(9

) O

rgan

ism

s th

at a

re s

usce

ptib

le t

o te

tracy

clin

e ar

e al

so c

onsi

dere

d su

scep

tible

to

doxy

cycl

ine

and

min

ocyc

line.

How

ever

, som

e or

gani

sms

that

are

inte

rmed

iate

or r

esis

tant

tote

tracy

clin

e m

ay b

e su

scep

tible

to d

oxyc

yclin

e or

min

ocyc

line

or b

oth.

UTe

tracy

clin

e≤

48

≥16

See

com

men

t (5)

.O

Dox

ycyc

line

≤4

8≥

16O

Min

ocyc

line

≤4

8≥

16FL

UO

RO

QU

INO

LON

ESB B

Cip

roflo

xaci

nLe

voflo

xaci

n ≤

1≤

22 4

≥4

≥8

U U U

Lom

eflo

xaci

n or

of

loxa

cin

orno

rflox

acin

≤2

≤2

≤4

4 4 8

≥8

≥8

≥16

OG

atifl

oxac

in≤

24

≥8

(10)

Thi

s br

eakp

oint

app

lies

to is

olat

es fr

om th

e ur

inar

y tra

ct o

nly.

FOLA

TE P

ATH

WAY

INH

IBIT

OR

SB

Trim

etho

prim

-sul

fam

etho

xazo

le≤

2/38

-≥

4/76

See

com

men

t (5)

.U

Sul

fona

mid

es≤

256

-≥

512

(11)

Sul

fisox

azol

e ca

n be

use

d to

repr

esen

t any

of t

he c

urre

ntly

ava

ilabl

e su

lfona

mid

epr

epar

atio

ns.

PHEN

ICO

LSC

Chl

oram

phen

icol

≤8

16≥

32(1

2) N

ot ro

utin

ely

repo

rted

on is

olat

es fr

om th

e ur

inar

y tra

ct.

See

com

men

t (5)

.

110

Tabl

e 2C

Stap

hylo

cocc

ussp

p.M

7-M

IC


January 2005 Vol. 25 No. 1Ta

ble

2C.

MIC

Inte

rpre

tive

Stan

dard

s (µµ

g/m

L) fo

rSt

aphy

loco

ccus

spp.

Min

imal

QC

Rec

omm

enda

tions

(S

ee T

able

3 f

or a

ccep

tabl

e Q

Cra

nges

.)

Stap

hylo

cocc

us a

ureu

sAT

CC

® 2

9213

Esch

eric

hia

coli

ATC

C®

3521

8 (F

or β

-lact

am/β

-lact

amas

e in

hibi

tor

com

bina

tions

)

Stap

hylo

cocc

us a

ureu

sAT

CC

® B

AA

-977

and

Sta

phyl

ococ

cus

aure

usAT

CC

®

BA

A-9

76

(for

qu

ality

as

sess

men

t of

th

ecl

inda

myc

in in

duct

ion

test

)

Test

ing

Con

ditio

ns

Med

ium

:B

roth

dilu

tion:

Cat

ion-

adju

sted

Mue

ller-

Hin

ton

brot

h (C

AM

HB

) C

AM

HB

plu

s 2%

NaC

l for

oxa

cilli

n, m

ethi

cilli

n, a

nd n

afci

llin;

CA

MH

B

supp

lem

ente

d to

50

µµ g/m

Lca

lciu

m fo

r da

ptom

ycin

A

gar d

ilutio

n: M

uelle

r-H

into

n ag

ar (M

HA

); A

gar

dilu

tion

is

curr

ently

not

rec

omm

ende

d fo

r da

ptom

ycin

. M

HA

plus

2%

NaC

l for

oxa

cilli

n, m

ethi

cilli

n, a

nd n

afci

llin

Inoc

ulum

:D

irect

col

ony

susp

ensi

on, e

quiv

alen

t to

a 0.

5 M

cFar

land

sta

ndar

dIn

cuba

tion:

33 to

35

°C (d

o no

t exc

eed

35 °

C);

ambi

ent a

ir; 1

6 to

20

hour

s; 2

4 ho

urs

for o

xaci

llin,

met

hici

llin,

naf

cilli

n, a

nd v

anco

myc

in Gen

eral

Com

men

ts

(1)

His

toric

ally,

resi

stan

ce to

the

peni

cilli

nase

-sta

ble

peni

cilli

ns (s

ee G

loss

ary

I) h

as b

een

refe

rred

to a

s “m

ethi

cilli

n re

sist

ance

,” th

us th

e ac

rony

ms

MR

SA

(for “

met

hici

llin-

resi

stan

t S. a

ureu

s”) o

r MR

S (f

or “m

ethi

cilli

n-re

sist

ant s

taph

yloc

occi

”) a

re s

till c

omm

only

use

d ev

en th

ough

met

hici

llin

is n

o lo

nger

the

agen

t of c

hoic

e fo

r tes

ting

ortre

atm

ent.

In th

is d

ocum

ent,

resi

stan

ce to

thes

e ag

ents

may

be

refe

rred

to u

sing

sev

eral

term

s (e

.g.,

“MR

S,”

“met

hici

llin

resi

stan

ce,”

“oxa

cilli

n re

sist

ance

”).

(2)

For

oxac

illin

-sus

cept

ible

Sta

phyl

ococ

cus

aure

usan

d co

agul

ase-

nega

tive

stap

hylo

cocc

i, re

sults

for

par

ente

ral a

nd o

ral c

ephe

ms,

ββ-la

ctam

/ββ-la

ctam

ase

inhi

bito

r com

bina

tions

, and

car

bape

nem

s, if

test

ed, s

houl

d be

repo

rted

acc

ordi

ng to

the

resu

lts g

ener

ated

usi

ng ro

utin

e in

terp

retiv

e cr

iteria

. See

com

men

t(3

) for

rep

ortin

g ββ -

lact

am r

esul

ts o

n ox

acill

in-r

esis

tant

str

ains

.

(3)

WA

RN

ING

:For

oxa

cilli

n-re

sist

ant S

. aur

eus

and

coag

ulas

e-ne

gativ

e st

aphy

loco

cci (

MR

S),

othe

r ββ -

lact

am a

gent

s, i.

e., p

enic

illin

s, ββ

-lact

am/ββ

-lact

amas

e in

hibi

tor

com

bina

tions

, cep

hem

s, a

nd c

arba

pene

ms

may

app

ear a

ctiv

e in

vitr

o bu

t are

not

effe

ctiv

e cl

inic

ally.

Res

ults

for t

hese

dru

gs s

houl

d be

repo

rted

as re

sist

ant o

r sho

uld

not b

e re

porte

d. T

his

is b

ecau

se m

ost c

ases

of d

ocum

ente

d M

RS

infe

ctio

ns h

ave

resp

onde

d po

orly

to β

-lact

am th

erap

y, o

r bec

ause

con

vinc

ing

clin

ical

dat

a ha

ve y

etto

be

pres

ente

d th

at d

ocum

ent c

linic

al e

ffica

cy fo

r tho

se a

gent

s.

(4)

Det

ectio

n of

oxa

cilli

n re

sist

ance

: Tes

ts fo

r m

ecA

or fo

r th

e pr

otei

n ex

pres

sed

by m

ecA

, the

pen

icill

in-b

indi

ng p

rote

in 2

a (P

BP

2a, a

lso

calle

d PB

P2')

are

the

mos

t ac

cura

te m

etho

ds f

or p

redi

ctio

n of

res

ista

nce

to o

xaci

llin

and

coul

d be

use

d to

con

firm

res

ults

for

isol

ates

of

sta

phyl

ococ

ci

from

ser

ious

infe

ctio

ns. I

sola

tes

of s

taph

yloc

occi

tha

t ar

e sh

own

to c

arry

the

mec

Age

ne, o

r th

at p

rodu

ce P

BP

2a, t

he m

ecA

gene

pro

duct

, sho

uld

be r

epor

ted

asox

acill

in r

esis

tant

. Iso

late

s th

at a

re n

ot s

how

n to

car

ry m

ecA

or d

o no

t pro

duce

PB

P2a

sho

uld

be r

epor

ted

as o

xaci

llin

susc

eptib

le if

oxa

cilli

n M

ICS

are

≤≤ 2

µµ g/m

L. B

ecau

se o

f the

rar

e oc

curr

ence

of r

esis

tanc

e m

echa

nism

s ot

her

than

mec

A, i

sola

tes

that

are

neg

ativ

e fo

r th

e m

ecA

gene

or

do n

ot p

rodu

cePB

P2a

, but

for

whi

ch M

ICs

are

≥≥4

µµ g/m

Lsh

ould

be

repo

rted

as

oxac

illin

res

ista

nt.

(5)

Rou

tine

test

ing

of u

rine

isol

ates

of S

. sap

roph

ytic

us is

not

adv

ised

, bec

ause

infe

ctio

ns re

spon

d to

con

cent

ratio

ns a

chie

ved

in u

rine

of a

ntim

icro

bial

age

nts

com

mon

lyus

ed to

trea

t acu

te, u

ncom

plic

ated

urin

ary

tract

infe

ctio

ns (e

.g.,

nitro

fura

ntoi

n, tr

imet

hopr

im ±

sul

fam

etho

xazo

le, o

r a fl

uoro

quin

olon

e).

(6)

For s

ome

orga

nism

/ant

imic

robi

al a

gent

com

bina

tions

, the

abs

ence

of r

esis

tant

stra

ins

prec

lude

s de

finin

g an

y re

sults

cat

egor

ies

othe

r tha

n “s

usce

ptib

le.”

For

stra

ins

yiel

ding

resu

lts s

ugge

stiv

e of

a “n

onsu

scep

tible

” cat

egor

y, o

rgan

ism

iden

tific

atio

n an

d an

timic

robi

al s

usce

ptib

ility

test

resu

lts s

houl

d be

con

firm

ed. S

ubse

quen

tly, t

heis

olat

es s

houl

d be

sav

ed a

nd s

ubm

itted

to a

refe

renc

e la

bora

tory

that

will

con

firm

resu

lts u

sing

a C

LSI/N

CC

LS re

fere

nce

dilu

tion

met

hod.

NO

TE:

Info

rmat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.


Tabl

e 2C

. (C

ontin

ued)


Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

RPE

NIC

ILLI

NS

(7)

Pen

icill

in-s

usce

ptib

le s

taph

yloc

occi

are

als

o su

scep

tible

to

othe

r pe

nici

llins

, β-

lact

am/β

-lact

amas

ein

hibi

tor

com

bina

tions

, ce

phem

s, a

nd c

arba

pene

ms

appr

oved

for

use

by

the

FDA

for

stap

hylo

cocc

alin

fect

ions

. Pen

icill

in-r

esis

tant

, oxa

cilli

n-su

scep

tible

stra

ins

are

resi

stan

t to

peni

cilli

nase

-labi

le p

enic

illin

s bu

tsu

scep

tible

to

othe

r pe

nici

llina

se-s

tabl

e pe

nici

llins

, β-

lact

am/β

-lact

amas

e in

hibi

tor

com

bina

tions

, re

leva

ntce

phem

s, a

nd c

arba

pene

ms.

Oxa

cilli

n-re

sist

ant s

taph

yloc

occi

are

resi

stan

t to

all c

urre

ntly

ava

ilabl

e β-

lact

aman

tibio

tics.

Thu

s, s

usce

ptib

ility

or

resi

stan

ce to

a w

ide

arra

y of

β-la

ctam

ant

ibio

tics

may

be

dedu

ced

from

test

ing

only

pen

icill

in a

nd o

xaci

llin.

Rou

tine

test

ing

of o

ther

pen

icill

ins,

β-la

ctam

/β-la

ctam

ase

inhi

bito

rco

mbi

natio

ns, c

ephe

ms,

and

car

bape

nem

s is

not

adv

ised

.

See

com

men

t (3)

. A

Pen

icill

in

≤0.

12-

≥0.

25(8

) R

esis

tant

stra

ins

of S

. aur

eus

prod

uce

beta

-lact

amas

e, a

nd th

e te

stin

g of

pen

icilli

n in

stea

d of

am

pici

llinis

pre

ferre

d. P

enic

illin

shou

ld b

e us

ed to

test

the

susc

eptib

ility

of a

ll st

aphy

loco

cci t

o al

l pen

icilli

nase

-labi

lepe

nici

llins,

suc

h as

am

pici

llin,

amox

icilli

n, a

zloc

illin,

car

beni

cillin

, m

ezlo

cillin

, pi

pera

cillin

, an

d tic

arci

llin. A

peni

cillin

MIC

of ≤

0.03

µg/

mL

usua

lly im

plie

s la

ck o

f β-la

ctam

ase

prod

uctio

n, a

nd M

ICs

of ≥

0.25

µg/

mL

shou

ld b

e co

nsid

ered

resi

stan

t; st

aphy

loco

cci w

ith p

enic

illin

MIC

s be

twee

n 0.

06 to

0.1

2 µg

/mL

may

or m

ayno

t pro

duce

β-la

ctam

ase,

and

an

indu

ced

beta

-lact

amas

e te

st c

an c

larif

y th

ese

MIC

s (s

ee M

7-A6

, Sec

tion

10.2

). A

posi

tive

β-la

ctam

ase

test

pre

dict

s re

sist

ance

to

peni

cillin

, am

pici

llin,

amox

icilli

n, c

arbe

nici

llin,

ticar

cillin

, m

ezlo

cillin

, an

d pi

pera

cillin

. Fo

r ox

acilli

n-re

sist

ant

stap

hylo

cocc

i, re

port

as r

esis

tant

or

do n

otre

port.

AO

xaci

llin

≤2

≤0.

25- -

≥4

≥0.

5Fo

r S. a

ureu

san

d S.

lugd

unen

sis.

For c

oagu

lase

-neg

ativ

e st

aphy

loco

cci,

exce

pt S

. lug

dune

nsis

.

(9)

Of t

he p

enic

illin

ase-

stab

le p

enic

illin

s, o

xaci

llin

may

be

test

ed, a

nd r

esul

ts c

an b

e ap

plie

d to

the

othe

rpe

nici

llina

se-s

tabl

e pe

nici

llins

, cl

oxac

illin

, di

clox

acill

in a

nd f

lucl

oxac

illin

. Te

stin

g of

oxa

cilli

n is

pre

ferr

ed,

sinc

e it

is m

ore

resi

stan

t to

degr

adat

ion

in s

tora

ge, a

nd b

ecau

se it

is m

ore

likel

y to

det

ect h

eter

ores

ista

ntst

rain

s. (S

ee th

e ta

ble

at th

e en

d of

this

tabl

e fo

r the

oxa

cilli

n ag

ar s

cree

n te

st fo

r S. a

ureu

s.)

(10)

Int

erpr

etiv

e cr

iteria

for c

oagu

lase

-neg

ativ

e st

aphy

loco

cci c

orre

late

with

the

pres

ence

or a

bsen

ce o

f the

gene

enc

odin

g m

ethi

cilli

n re

sist

ance

(m

ecA

) fo

r S.

epi

derm

idis

.Th

ese

inte

rpre

tive

crite

ria m

ay o

verc

all

resi

stan

ce fo

r ot

her

coag

ulas

e-ne

gativ

e st

aphy

loco

cci (

e.g.

, S. s

apro

phyt

icus

). Fo

r se

rious

infe

ctio

ns w

ithco

agul

ase-

nega

tive

stap

hylo

cocc

i oth

er th

an S

. epi

derm

idis

,tes

ting

for

mec

Aor

the

prot

ein

expr

esse

d by

mec

A, t

he p

enic

illin

bin

ding

pro

tein

2a

(PB

P2a

, “al

so k

now

n as

” PB

P2'

) may

be

appr

opria

te fo

r stra

ins

for

whi

ch th

e ox

acill

in M

ICs

are

0.5

to 2

µg/

mL.

(11)

The

resu

lts o

f dis

k di

ffusi

on te

sts

usin

g a

30-µ

g ce

foxi

tin d

isk

and

alte

rnat

e br

eakp

oint

s (s

ee b

ox a

t the

end

of t

his

tabl

e) c

an b

e us

ed t

o pr

edic

t m

ecA-

med

iate

d re

sist

ance

in s

taph

yloc

occi

. C

ompa

red

to M

ICte

sts,

the

cefo

xitin

dis

k te

st is

equ

ival

ent i

n se

nsiti

vity

and

spe

cific

ity fo

r S.

aur

eus.

For

coag

ulas

e-ne

gativ

e st

aphy

loco

cci,

the

cefo

xitin

dis

k te

st,

whe

n co

mpa

red

to o

xaci

llin

MIC

tes

ts,

has

equa

lse

nsiti

vity

but

hig

her

spec

ifici

ty (i

.e.,

the

cefo

xitin

dis

k te

st is

mor

e ac

cura

te th

an th

e ox

acill

in M

ICte

st fo

r ide

ntify

ing

oxac

illin

-sus

cept

ible

str

ains

).

OA

mpi

cilli

n≤

0.25

-

≥0.

5(1

2) C

lass

repr

esen

tativ

e fo

r am

pici

llin

and

amox

icill

in.

(13)

For

oxa

cilli

n-re

sist

ant s

taph

yloc

occi

, rep

ort a

s re

sist

ant o

r do

not r

epor

t.O

Met

hici

llin

≤8

-≥

16

(14)

For

use

with

S. a

ureu

son

ly.

ON

afci

llin

≤2

-≥

4(1

5) F

or u

se w

ith S

. aur

eus

only.

Tabl

e 2C

Stap

hylo

cocc

ussp

p.M

7-M

IC

112

Tabl

e 2C

Stap

hylo

cocc

ussp

p.M

7-M

IC



Tabl

e 2C

. (C

ontin

ued)

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

Rββ -

LAC

TAM

/ββ-L

AC

TAM

ASE

INH

IBIT

OR

CO

MB

INAT

ION

S(1

6) F

or o

xaci

llin-

resi

stan

t sta

phyl

ococ

ci, r

epor

t as

resi

stan

t or d

o no

t rep

ort.

OA

mox

icill

in-c

lavu

lani

c ac

id≤

4/2

- ≥

8/4

OA

mpi

cilli

n-su

lbac

tam

≤8/

416

/8≥

32/1

6 O

Pip

erac

illin

-tazo

bact

am≤

8/4

-≥

16/4

OTi

carc

illin

-cla

vula

nic

acid

≤8/

2-

≥16

/2C

EPH

EMS

(PA

REN

TER

AL)

(Inc

ludi

ng c

epha

losp

orin

s I,

II, II

I, an

d IV

. S

ee c

omm

ent (

7).

Plea

se r

efer

to G

loss

ary

I.)(1

7) F

or o

xaci

llin-

resi

stan

t sta

phyl

ococ

ci, r

epor

t as

resi

stan

t or d

o no

t rep

ort.

OC

efam

ando

le≤

816

≥32

OC

efaz

olin

≤8

16≥

32O

Cef

epim

e≤

816

≥32

OC

efm

etaz

ole

≤16

32≥

64O

Cef

onic

id≤

816

≥32

OC

efop

eraz

one

≤16

32≥

64O

Cef

otax

ime

≤8

16-3

2≥

64O

Cef

otet

an≤

1632

≥64

OC

efox

itin

≤8

16≥

32S

ee c

omm

ent (

11)

OC

efta

zidi

me

≤8

16≥

32O

Cef

tizox

ime

≤8

16-3

2≥

64O

Cef

triax

one

≤8

16-3

2≥

64O

Cef

urox

ime

sodi

um (p

aren

tera

l)≤

816

≥32

OC

epha

loth

in≤

816

≥32

OM

oxal

acta

m≤

816

-32

≥64

CEP

HEM

S (O

RA

L)(1

8) F

or o

xaci

llin-

resi

stan

t sta

phyl

ococ

ci, r

epor

t as

resi

stan

t or d

o no

t rep

ort.

OC

efac

lor

≤8

16≥

32O

Cef

dini

r ≤

12

≥4

OC

efpo

doxi

me

≤2

4≥

8O

Cef

proz

il ≤

816

≥32

OC

efur

oxim

e ax

etil

(ora

l)≤

48-

16≥

32O

Lora

carb

ef

≤8

16≥

32C

AR

BA

PEN

EMS

See

com

men

t (7)

.(1

9) F

or o

xaci

llin-

resi

stan

t sta

phyl

ococ

ci, r

epor

t as

resi

stan

t or d

o no

t rep

ort.

OE

rtape

nem

≤2

4≥

8O

Imip

enem

≤4

8≥

16O

Mer

open

em≤

48

≥16

113

Tabl

e 2C

Stap

hylo

cocc

ussp

p.M

7-M

IC


For Use With M7-A6–MIC Testing M100-S15Ta

ble

2C. (

Con

tinue

d)Te

st/R

epor

tG

roup

Ant

imic

robi

al A

gent

MIC

(µµg/

mL)

Inte

rpre

tive

Stan

dard

Com

men

ts

SI

RG

LYC

OPE

PTID

ESB

Vanc

omyc

in≤

48-

16≥

32(2

0) V

anco

myc

in-r

esis

tant

S.

aure

us(V

RSA

) st

rain

s (M

ICs

≥32

µg/m

L) a

rere

liabl

y de

tect

ed b

y th

e br

oth

mic

rodi

lutio

n re

fere

nce

met

hod.

Whe

n us

ing

othe

rM

IC m

etho

ds th

at h

ave

not b

een

valid

ated

to d

etec

t VR

SA, B

HI v

anco

myc

in a

gar

scre

en p

late

s co

ntai

ning

6 µµ

g/m

Lof

van

com

ycin

, su

ch a

s th

ose

used

for

dete

ctio

n of

van

com

ycin

-res

ista

nt e

nter

ococ

ci (

see

M7-

Tabl

e 2D

), sh

ould

be

inoc

ulat

ed to

enh

ance

the

sens

itivi

ty o

f det

ectin

g va

ncom

ycin

-res

ista

nt s

trai

ns.

(21)

S

end

any

stap

hylo

cocc

i det

erm

ined

to

have

an

elev

ated

MIC

for

van

com

ycin

(MIC

≥4

µg/m

L) to

a re

fere

nce

labo

rato

ry.

Inv.

Teic

opla

nin

≤8

16≥

32LI

POPE

PTID

ESB

Dap

tom

ycin

≤≤1

--

See

com

men

t (6)

.A

MIN

OG

LYC

OSI

DES

CG

enta

mic

in≤

48

≥16

OA

mik

acin

≤16

32≥

64O

Kan

amyc

in≤

1632

≥64

ON

etilm

icin

≤8

16≥

32O

Tobr

amyc

in≤

48

≥16

MA

CR

OLI

DES

B B B

Azi

thro

myc

in o

rcl

arith

rom

ycin

or

eryt

hrom

ycin

≤2

≤2

≤0.

5

4 4 1-4

≥8

≥8

≥8

(22)

N

ot r

outin

ely

test

ed a

nd r

epor

ted

agai

nst

orga

nism

s is

olat

ed f

rom

the

urin

ary

tract

.

OD

irith

rom

ycin

≤2

4≥

8K

ETO

LID

ESB

Telit

hrom

ycin

≤1

2≥

4

TETR

AC

YCLI

NES

CTe

tracy

clin

e≤

48

≥16

(23)

Org

anis

ms

that

are

sus

cept

ible

to te

tracy

clin

e ar

e al

so c

onsi

dere

d su

scep

tible

todo

xycy

clin

e an

d m

inoc

yclin

e.

How

ever

, so

me

orga

nism

s th

at a

re i

nter

med

iate

or

resi

stan

t to

tetra

cycl

ine

may

be

susc

eptib

le to

dox

ycyc

line

or m

inoc

yclin

e or

bot

h.O

Dox

ycyc

line

≤4

8≥

16O

Min

ocyc

line

≤4

8≥

16FL

UO

RO

QU

INO

LON

ES(2

4)

Stap

hylo

cocc

us s

pp.

may

dev

elop

res

ista

nce

durin

g pr

olon

ged

ther

apy

with

quin

olon

es. T

here

fore

, iso

late

s th

at a

re in

itial

ly s

usce

ptib

le m

ay b

ecom

e re

sist

ant w

ithin

thre

e to

four

day

s af

ter i

nitia

tion

of th

erap

y. T

estin

g of

repe

at is

olat

es m

ay b

e w

arra

nted

.C C C C C

Cip

roflo

xaci

n or

levo

floxa

cin

orof

loxa

cin

Gat

iflox

acin

or

mox

iflox

acin

≤1

≤≤1

≤≤1

≤≤0.

5≤≤

0.5

2 2 2 1 1

≥4

≥≥4

≥≥4

≥≥2

≥≥2

U ULo

mef

loxa

cin

orno

rflox

acin

≤2

≤4

4 8≥

8≥

16

114

Tabl

e 2C

Stap

hylo

cocc

ussp

p.M

7-M

IC



Tabl

e 2C

. (C

ontin

ued)

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rd

Com

men

ts

SI

RFL

UO

RO

QU

INO

LON

ES (C

ontin

ued)

OE

noxa

cin

≤2

4≥

8(2

5) F

DA

appr

oved

for S

. sap

roph

ytic

usan

d S.

epi

derm

idis

(not

S. a

ureu

s).

OG

repa

floxa

cin

≤1

2 ≥

4O

Spar

floxa

cin

≤0.

51

≥2

Inv.

Fler

oxac

in≤

24

≥8

NIT

RO

FUR

AN

TOIN

SU

Nitr

ofur

anto

in≤

3264

≥12

8LI

NC

OSA

MID

ESB

C

linda

myc

in

≤0.

51-

2≥

4(2

6) M

acro

lide-

resi

stan

t iso

late

s of

S. a

ureu

s an

d co

agul

ase-

nega

tive

Stap

hylo

cocc

ussp

p.m

ay h

ave

cons

titut

ive

or in

duci

ble

resi

stan

ce to

clin

dam

ycin

[met

hyla

tion

of th

e 23

S rR

NA

enco

ded

by t

he e

rmge

ne a

lso

refe

rred

to

as M

LSB

(mac

rolid

e, li

ncos

omid

e, a

nd t

ype

Bst

rept

ogra

min

) re

sist

ance

] or

may

be

resi

stan

t on

ly t

o m

acro

lides

(ef

flux-

mec

hani

smen

code

d by

the

msr

Age

ne).

Indu

cibl

e cl

inda

myc

in r

esis

tanc

e ca

n be

det

ecte

d us

ing

adi

sk a

ppro

xim

atio

n te

st b

y pl

acin

g a

2-µg

clin

dam

ycin

dis

k 15

mm

aw

ay fr

om th

e ed

ge o

fa

15-µ

g er

ythr

omyc

in d

isk

on a

sta

ndar

d bl

ood

agar

pla

te u

sed

for

the

inoc

ulum

pur

itych

eck.

Fol

low

ing

incu

batio

n, o

rgan

ism

s th

at d

o no

t sho

w fl

atte

ning

of t

he c

linda

myc

in z

one

shou

ld b

e re

porte

d as

clin

dam

ycin

sus

cept

ible

. O

rgan

ism

s th

at s

how

fla

tteni

ng o

f th

ecl

inda

myc

in z

one

adja

cent

to

the

eryt

hrom

ycin

dis

k (r

efer

red

to a

s a

“D”

zone

) ha

vein

duci

ble

clin

dam

ycin

resi

stan

ce. S

uch

isol

ates

sho

uld

be re

porte

d as

clin

dam

ycin

resi

stan

t.A

com

men

t tha

t "Th

is is

olat

e is

pre

sum

ed to

be

resi

stan

t bas

ed o

n de

tect

ion

of in

duci

ble

clin

dam

ycin

res

ista

nce.

Clin

dam

ycin

may

stil

l be

effe

ctiv

e in

som

e pa

tient

s."

may

be

incl

uded

. For

qua

lity

cont

rol/q

ualit

y as

sess

men

t rec

omm

enda

tions

, ref

er to

Tab

le 3

of

M2.

See

com

men

t (22

).

FOLA

TE P

ATH

WAY

INH

IBIT

OR

SB

Tr

imet

hopr

im-s

ulfa

met

hoxa

zole

≤2/

38-

≥4/

76U

Sul

fona

mid

es≤

256

-≥

512

(27)

S

ulfis

oxaz

ole

can

be u

sed

to r

epre

sent

any

of

the

curr

ently

ava

ilabl

e su

lfona

mid

epr

epar

atio

ns.

UTr

imet

hopr

im≤

8-

≥16

PHEN

ICO

LSC

Chl

oram

phen

icol

≤8

16≥

32S

ee c

omm

ent (

22).

AN

SAM

YCIN

SC

Rifa

mpi

n≤

12

≥4

(28)

Rx:

Rifa

mpi

n sh

ould

not

be

used

alo

ne fo

r che

mot

hera

py.

STR

EPTO

GR

AM

INS

CQ

uinu

pris

tin-d

alfo

pris

tin≤

12

≥4

OXA

ZOLI

DIN

ON

ESB

Line

zolid

≤4

--

See

com

men

t (6)

.



Disk Diffusion Testa for Prediction of mecA-mediated Resistance in StaphylococciAntimicrobial

Agent(Disk Content)

Organism Group Zone Diameter,Nearest Whole mm

Comments

Cefoxitin (30 µg) S. aureus and S.lugdunensis

≤ 19 ≥ 20 (29) S. aureus for whichcefoxitin disk diffusion zonesare ≤ 19 mm should bereported as oxacillin resistant.Those for which cefoxitin zonesare ≥ 20 mm should be reportedas oxacillin susceptible.

Coagulase-negativestaphylococci exceptS. lugdunensis

≤ 24 ≥ 25 (30) Coagulase-negativestaphylococci for which cefoxitindisk diffusion zones are ≤ 24mm should be reported asoxacillin resistant. Those forwhich cefoxitin zones are ≥ 25mm should be reported asoxacillin susceptible.

a Use standard disk diffusion testing conditions and incubate for 24 hours; however, results may be reported after18 hours incubation if resistant. Read the cefoxitin disk test using reflected light.

Table 2C. (Continued)

Tabl

e 2C

Stap

hylo

cocc

ussp

p.M

7-M

IC

Oxacillin-Salt Agar Screening Test for Staphylococcus aureus

Screen Test Oxacillin Resistance

Medium MHA with NaCl (4% w/v; 0.68 mol/L)Antimicrobial concentration 6 µg/mL oxacillin

Inoculum Direct colony suspension to obtain 0.5 McFarland turbidityUsing a 1-µL loop that was dipped in the suspension, spot an area 10 to 15mm in diameter. Alternatively, using a swab dipped in the suspension andexpressed, spot a similar area or streak an entire quadrant.

Incubation conditionsIncubation length

35 °C; ambient air 24 hours

Results >1 colony = resistantExamine carefully with transmitted light for >1 colony or light film of growth.

QC Recommendations Staphylococcus aureus ATCC® 29213 - Susceptible Staphylococcus aureus ATCC® 43300 - Resistant

Test

ing

Con

ditio

ns

Med

ium

:B

roth

dilu

tion:

Cat

ion-

adju

sted

Mue

ller-

Hin

ton

brot

h (C

AM

HB

); C

AM

HB

sup

plem

ente

d to

50

µµ g/m

Lca

lciu

m fo

rda

ptom

ycin

Aga

r dilu

tion:

Mue

ller-

Hin

ton

agar

(MH

A);

Aga

r di

lutio

n is

cu

rren

tly n

ot r

ecom

men

ded

for

dapt

omyc

in

Inoc

ulum

:G

row

th m

etho

d or

dire

ct c

olon

y su

spen

sion

, equ

ival

ent t

o a

0.5

McF

arla

nd s

tand

ard

Incu

batio

n:35

°C

±2

degr

ees;

am

bien

t air;

16

to 2

0 ho

urs;

24

hour

s fo

r va

ncom

ycin


116

Tabl

e 2D

Ente

roco

ccus

spp.

M7-

MIC


Tabl

e 2D

. M

IC In

terp

retiv

e St

anda

rds

(µµg/

mL)

for

Ente

roco

ccus

spp.

Min

imal

QC

Rec

omm

enda

tions

(See

Tab

le 3

for A

ccep

tabl

e Q

CR

ange

s.)

Ente

roco

ccus

faec

alis

ATC

C®

2921

2

Gen

eral

Com

men

ts

(1)

WA

RN

ING

:

For

Ente

roco

ccus

sp

p.,

ceph

alos

porin

s,

amin

ogly

cosi

des

(exc

ept

for

high

-leve

l re

sist

ance

sc

reen

ing)

, cl

inda

myc

in,

and

trim

etho

prim

-su

lfam

etho

xazo

le m

ay a

ppea

r act

ive

in v

itro

but a

re n

ot e

ffect

ive

clin

ical

ly, a

nd is

olat

es s

houl

d no

t be

repo

rted

as s

usce

ptib

le.

(2)

Syn

ergy

bet

wee

n am

pici

llin,

pen

icill

in, o

r van

com

ycin

and

an

amin

ogly

cosi

de c

an b

e pr

edic

ted

for e

nter

ococ

ci b

y us

ing

a hi

gh-le

vel a

min

ogly

cosi

de (g

enta

mic

inan

d st

rept

omyc

in)

scre

enin

g te

st. O

ther

am

inog

lyco

side

s ne

ed n

ot b

e te

sted

, bec

ause

thei

r ac

tiviti

es a

gain

st e

nter

ococ

ci a

re n

ot s

uper

ior

to g

enta

mic

in a

ndst

rept

omyc

in.

(3)

Bec

ause

of l

imite

d al

tern

ativ

es, c

hlor

amph

enic

ol, e

ryth

rom

ycin

, tet

racy

clin

e (o

r dox

ycyc

line

or m

inoc

yclin

e), a

nd ri

fam

pin

may

be

test

ed fo

r van

com

ycin

-res

ista

nten

tero

cocc

i (V

RE

), an

d co

nsul

tatio

n w

ith a

n in

fect

ious

dis

ease

pra

ctiti

oner

is re

com

men

ded.

(4)

For

som

e or

gani

sm/a

ntim

icro

bial

age

nt c

ombi

natio

ns,

the

abse

nce

of r

esis

tant

str

ains

pre

clud

es d

efin

ing

any

resu

lts c

ateg

orie

s ot

her

than

“sus

cept

ible

.”Fo

r st

rain

s yi

eldi

ng r

esul

ts s

ugge

stiv

e of

a “

nons

usce

ptib

le”

cate

gory

, org

anis

m id

entif

icat

ion

and

antim

icro

bial

sus

cept

ibili

ty t

est

resu

lts s

houl

d be

con

firm

ed. S

ubse

quen

tly, t

he is

olat

es s

houl

d be

sav

ed a

nd s

ubm

itted

to

a re

fere

nce

labo

rato

ry t

hat

will

con

firm

res

ults

usi

ng a

CLS

I/NC

CLS

ref

eren

ce d

ilutio

n m

etho

d.

NO

TE:

Info

rmat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.


117

Tabl

e 2D

Ente

roco

ccus

spp.

M7-

MIC


Tabl

e 2D

. (C

ontin

ued)

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

RPE

NIC

ILLI

NS

A AP

enic

illin

or

ampi

cilli

n≤

8≤

8- -

≥16

≥16

(5)

Am

pici

llin

is t

he c

lass

rep

rese

ntat

ive

for

ampi

cilli

n an

d am

oxic

illin

. A

mpi

cilli

nre

sults

may

be

used

to p

redi

ct s

usce

ptib

ility

to a

mox

icill

in-c

lavu

lani

c ac

id, a

mpi

cilli

n-su

lbac

tam

, pi

pera

cilli

n,

and

pipe

raci

llin-

tazo

bact

am

amon

g no

n-β-

lact

amas

e-pr

oduc

ing

ente

roco

cci.

Am

pici

llin

susc

eptib

ility

can

be

used

to

pred

ict

imip

enem

susc

eptib

ility

pro

vidi

ng th

e sp

ecie

s is

con

firm

ed to

be

E. fa

ecal

is.

(6)

Pen

icill

in s

usce

ptib

ility

may

be

used

to

pred

ict

the

susc

eptib

ility

to

ampi

cilli

n,am

oxic

illin

, am

pici

llin-

sulb

acta

m,

amox

icill

in-c

lavu

lani

c ac

id,

pipe

raci

llin,

an

dpi

pera

cilli

n-ta

zoba

ctam

for n

on-β

-lact

amas

e-pr

oduc

ing

ente

roco

cci.

(7)

Rx:

The

”su

scep

tible

” ca

tego

ry fo

r pe

nici

llin

or a

mpi

cilli

n im

plie

s th

e ne

ed fo

rhi

gh-d

ose

ther

apy

for

serio

us e

nter

ococ

cal

infe

ctio

ns.

Ent

eroc

occa

l en

doca

rditi

sre

quire

s co

mbi

ned

ther

apy

with

hig

h-do

se p

enic

illin

(or

hig

h-do

se a

mpi

cilli

n, o

rva

ncom

ycin

or t

eico

plan

in) p

lus

gent

amic

in o

r stre

ptom

ycin

for b

acte

ricid

al a

ctio

n.

(8)

Bec

ause

am

pici

llin

or p

enic

illin

res

ista

nce

amon

g en

tero

cocc

i du

e to

β-

lact

amas

e pr

oduc

tion

is n

ot re

liabl

y de

tect

ed u

sing

rout

ine

dilu

tion

met

hods

, a d

irect

,ni

troce

fin-b

ased

β-la

ctam

ase

test

is re

com

men

ded

for b

lood

and

cer

ebro

spin

al fl

uid

isol

ates

. A

posi

tive

β-la

ctam

ase

test

pre

dict

s re

sist

ance

to

peni

cilli

n, a

s w

ell

asam

ino-

, car

boxy

-, an

d ur

eido

peni

cilli

ns.

GLY

CO

PEPT

IDES

BVa

ncom

ycin

≤4

8-16

≥32

(9)

Whe

n te

stin

g va

ncom

ycin

, pl

ates

sho

uld

be h

eld

a fu

ll 24

hou

rs f

or a

ccur

ate

dete

ctio

n of

res

ista

nce.

For

isol

ates

with

van

com

ycin

MIC

s of

8-1

6 µg

/mL,

per

form

bioc

hem

ical

test

s fo

r id

entif

icat

ion

as li

sted

und

er “

Vanc

omyc

in R

esis

tanc

e” te

st a

tth

e en

d of

this

tabl

e.S

ee c

omm

ents

(2) a

nd (7

).In

v.Te

icop

lani

n ≤

816

≥32

See

com

men

ts (2

) and

(7).

LIPO

PEPT

IDES

BD

apto

myc

in≤≤

4-

-Se

e co

mm

ent (

4).

TETR

AC

YCLI

NES

See

com

men

t (3)

.C

Tetra

cycl

ine

≤4

8≥

16(1

0) O

rgan

ism

s th

at a

re s

usce

ptib

le to

tetra

cycl

ine

are

also

con

side

red

susc

eptib

leto

dox

ycyc

line

and

min

ocyc

line.

How

ever

, som

e or

gani

sms

that

are

inte

rmed

iate

or

resi

stan

t to

tetra

cycl

ine

may

be

susc

eptib

le to

dox

ycyc

line

or m

inoc

yclin

e or

bot

h.O

Dox

ycyc

line

≤4

8≥

16O

Min

ocyc

line

≤4

8≥

16M

AC

RO

LID

ESC

Ery

thro

myc

in≤

0.5

1-4

≥8

(11)

Not

rout

inel

y te

sted

and

repo

rted

on is

olat

es fr

om th

e ur

inar

y tra

ct.

118

Tabl

e 2D

Ente

roco

ccus

spp.

M7-

MIC


Tabl

e 2D

. (C

ontin

ued)

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

RFL

UO

RO

QU

INO

LON

ESU U U

Cip

roflo

xaci

nLe

voflo

xaci

nN

orflo

xaci

n

≤1

≤2

≤4

2 4 8

≥4

≥8

≥16

OG

atifl

oxac

in≤

24

≥8

(12)

Thi

s br

eakp

oint

app

lies

to is

olat

es fr

om th

e ur

inar

y tra

ct o

nly.

PHEN

ICO

LSC

Chl

oram

phen

icol

≤8

16≥

32S

ee c

omm

ent (

3).

See

com

men

t (11

).A

NSA

MYC

INS

CR

ifam

pin

≤1

2≥

4(1

3) R

x:R

ifam

pin

shou

ld n

ot b

e us

ed a

lone

for c

hem

othe

rapy

.S

ee c

omm

ent (

3).

FOSF

OM

YCIN

SU

Fosf

omyc

in≤

6412

8≥

256

(14)

For

use

with

E. f

aeca

lison

ly. T

he a

ppro

ved

met

hod

of M

IC s

usce

ptib

ility

test

ing

is a

gar

dilu

tion.

Aga

r m

edia

sho

uld

be s

uppl

emen

ted

with

25

µg/m

Lof

glu

cose

-6-p

hosp

hate

. Bro

thdi

lutio

n te

stin

g sh

ould

not

be

perfo

rmed

.N

ITR

OFU

RA

NTO

INS

UN

itrof

uran

toin

≤32

64≥

128

STR

EPTO

GR

AM

INS

BQ

uinu

pris

tin-d

alfo

pris

tin≤

12

≥4

OXA

ZOLI

DIN

ON

ESB

Line

zolid

≤2

4≥

8




Scre

enin

g Te

sts

for

Hig

h-Le

vel A

min

ogly

cosi

de R

esis

tanc

e an

d Va

ncom

ycin

Res

ista

nce

in E

nter

ococ

cus

spp.

Foot

note

a .E

ven

thou

gh n

ot a

s w

idel

y av

aila

ble,

dex

trose

pho

spha

te a

gar a

nd b

roth

hav

e be

en s

how

n in

lim

ited

test

ing

to p

erfo

rm c

ompa

rabl

y.

Scr

een

Test

Gen

tam

icin

HLA

RSt

rept

omyc

in H

LAR

Va

ncom

ycin

Res

ista

nce

Med

ium

BH

Iabr

oth

or a

gar

BH

Iabr

oth

or a

gar

BH

I aga

r

Ant

imic

robi

al

conc

entra

tion

500

µg/m

LB

roth

: 100

0 µg

/mL

Aga

r: 20

00 µ

g/m

L6

µg/m

L

Inoc

ulum

Gro

wth

met

hod

or d

irect

col

ony

susp

ensi

on t

oob

tain

0.5

McF

arla

nd tu

rbid

ity

Aga

r –

10 µ

Lof

a 0

.5 M

cFar

land

sus

pens

ion

spot

ted

onto

aga

r sur

face

Bro

th –

sta

ndar

d br

oth

dilu

tion

reco

mm

enda

tions

Gro

wth

met

hod

or d

irect

col

ony

susp

ensi

on to

obt

ain

0.5

McF

arla

nd tu

rbid

ity

Aga

r – 1

0 µL

of a

0.5

McF

arla

nd s

uspe

nsio

n sp

otte

don

to a

gar s

urfa

ce

Bro

th –

sta

ndar

d br

oth

dilu

tion

reco

mm

enda

tions

Gro

wth

met

hod

or d

irect

col

ony

susp

ensi

on to

obta

in 0

.5 M

cFar

land

turb

idity

1-10

µL

of a

0.5

McF

arla

nd s

uspe

nsio

n sp

otte

don

to a

gar s

urfa

ce

Incu

batio

n co

nditi

ons

35 °

C; a

mbi

ent a

ir 35

°C

; am

bien

t air

35

°C

; am

bien

t air

Incu

batio

n le

ngth

24 h

ours

24

- 48

hou

rs (i

f sus

cept

ible

at 2

4 ho

urs,

rein

cuba

te)

24 h

ours

Res

ults

Aga

r: >1

col

ony

= re

sist

ant

Bro

th: a

ny g

row

th =

resi

stan

t

Res

ista

nt –

will

not

be

syne

rgis

tic w

ith c

ell-w

all-

activ

e ag

ent (

e.g.

, am

pici

llin,

pen

icill

in,

vanc

omyc

in)

Sus

cept

ible

– w

ill b

e sy

nerg

istic

with

cel

l-wal

l-ac

tive

agen

t th

at

is

also

su

scep

tible

(e

.g.,

ampi

cilli

n, p

enic

illin

, van

com

ycin

)

Aga

r: >1

col

ony

= re

sist

ant

Bro

th: a

ny g

row

th =

resi

stan

t

Res

ista

nt –

will

not

be

syne

rgis

tic w

ith c

ell-w

all-a

ctiv

eag

ent (

e.g.

, am

pici

llin,

pen

icill

in, v

anco

myc

in)

Sus

cept

ible

– w

ill b

e sy

nerg

istic

with

cel

l-wal

l-act

ive

agen

t to

w

hich

th

e is

olat

e is

su

scep

tible

(e

.g.,

ampi

cilli

n, p

enic

illin

, van

com

ycin

)

>1 c

olon

y =

pres

umpt

ive

resi

stan

ce

Per

form

van

com

ycin

MIC

and

test

for

mot

ility

and

pigm

ent

prod

uctio

n to

di

stin

guis

h sp

ecie

s w

ithac

quire

d re

sist

ance

(Va

nAan

d Va

nB)

from

tho

sew

ith

intri

nsic

, in

term

edia

te-le

vel

resi

stan

ce

tova

ncom

ycin

(Va

nC)

such

as

E. g

allin

arum

and

E.ca

ssel

iflav

us,w

hich

ofte

n gr

ow o

n th

e va

ncom

ycin

scre

en p

late

. In

con

trast

to

othe

r en

tero

cocc

i, E.

cass

elifl

avus

,an

d E.

gal

linar

umw

ith v

anco

myc

inM

ICs

of

8-16

µg

/mL

(inte

rmed

iate

) di

ffer

from

vanc

omyc

in-r

esis

tant

en

tero

cocc

i fo

r in

fect

ion

cont

rol p

urpo

ses.

QC

Rec

omm

enda

tions

E. fa

ecal

isAT

CC

®29

212

– S

usce

ptib

le

E. fa

ecal

is A

TCC

® 5

1299

– R

esis

tant

E.

faec

alis

ATC

C®

2921

2 –

Sus

cept

ible

E.

faec

alis

ATC

C®

512

99 –

Res

ista

ntE.

faec

alis

ATC

C®

2921

2 –

Sus

cept

ible

E.

faec

alis

ATC

C®

5129

9 –

Res

ista

nt

Tabl

e 2D

Ente

roco

ccus

spp.

M7-

MIC

Tabl

e 2D

. (C

ontin

ued)


120

Tabl

e 2E

Hae

mop

hilu

sspp

.M

7-M

IC


Tabl

e 2E

. M

IC In

terp

retiv

e St

anda

rds

(µµg/

mL)

for

Hae

mop

hilu

ssp

p. Min

imal

QC

Rec

omm

enda

tions

(See

Tab

le 3

Afo

r acc

epta

ble

QC

rang

es.)

Hae

mop

hilu

s in

fluen

zae

ATC

C®

4924

7H

aem

ophi

lus

influ

enza

eAT

CC

®49

766

Esch

eric

hia

coli

ATC

C®

352

18 (w

hen

test

ing

amox

icill

in-c

lavu

lani

c ac

id)

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

RPE

NIC

ILLI

NS

AA

mpi

cilli

n≤

12

≥4

(5)

The

resu

lts o

f am

pici

llin

susc

eptib

ility

test

s sh

ould

be

used

to p

redi

ct th

e ac

tivity

of

amox

icill

in. T

he m

ajor

ity o

f iso

late

s of

H. i

nflu

enza

eth

at a

re r

esis

tant

to a

mpi

cilli

n an

dam

oxic

illin

pro

duce

a T

EM

-type

β-la

ctam

ase.

In

mos

t ca

ses,

a d

irect

β-la

ctam

ase

test

can

prov

ide

a ra

pid

mea

ns o

f det

ectin

g am

pici

llin

and

amox

icill

in re

sist

ance

.

(6)

Rar

e β-

lact

amas

e-ne

gativ

e, a

mpi

cilli

n-re

sist

ant

(BLN

AR

) st

rain

s of

H.

influ

enza

esh

ould

be

co

nsid

ered

re

sist

ant

to

amox

icill

in-c

lavu

lani

c ac

id,

ampi

cilli

n-su

lbac

tam

,ce

facl

or,

cefa

man

dole

, ce

feta

met

, ce

foni

cid,

ce

fpro

zil,

cefu

roxi

me,

lo

raca

rbef

, an

dpi

pera

cilli

n-ta

zoba

ctam

des

pite

app

aren

t in

vitro

susc

eptib

ility

of s

ome

BLN

AR

stra

ins

toth

ese

agen

ts.

Test

ing

Con

ditio

ns

Med

ium

:B

roth

dilu

tion:

Hae

mop

hilu

sTe

st M

ediu

m

(HTM

) bro

thIn

ocul

um:

Dire

ct c

olon

y su

spen

sion

, equ

ival

ent t

o a

0.5

McF

arla

nd s

tand

ard

Incu

batio

n:35

°C

±2

degr

ees;

ambi

ent a

ir; 2

0 to

24

hour

s

Gen

eral

Com

men

ts

(1)

Onl

y re

sults

of

test

ing

with

am

pici

llin,

one

of

the

third

-gen

erat

ion

ceph

alos

porin

s, c

hlor

amph

enic

ol,

and

mer

open

em s

houl

d be

rep

orte

d ro

utin

ely

with

CS

Fis

olat

es o

f Hae

mop

hilu

s in

fluen

zae .

(2)

Am

oxic

illin

-cla

vula

nic

acid

, azi

thro

myc

in, c

larit

hrom

ycin

, cef

aclo

r, ce

fpro

zil,

lora

carb

ef, c

efdi

nir,

cefix

ime,

cef

podo

xim

e, a

nd c

efur

oxim

e ax

etil

are

oral

age

nts

that

may

be

used

as

empi

ric th

erap

y fo

r res

pira

tory

trac

t inf

ectio

ns d

ue to

Hae

mop

hilu

ssp

p. T

he re

sults

of s

usce

ptib

ility

test

s w

ith th

ese

antim

icro

bial

age

nts

are

ofte

n no

t use

ful f

or m

anag

emen

t of i

ndiv

idua

l pat

ient

s. H

owev

er, s

usce

ptib

ility

test

ing

of H

aem

ophi

lus

spp.

with

thes

e co

mpo

unds

may

be

appr

opria

te fo

rsu

rvei

llanc

e or

epi

dem

iolo

gic

stud

ies.

(3)

To m

ake

Hae

mop

hilu

sTe

st M

ediu

m: a

fres

h he

mat

in s

tock

sol

utio

n is

pre

pare

d by

dis

solv

ing

50 m

g of

hem

atin

pow

der i

n 10

0 m

Lof

0.0

1 N

(0.0

1 m

ol/L

) NaO

Hw

ith h

eat a

nd s

tirrin

g un

til th

e po

wde

r is

diss

olve

d th

orou

ghly.

Thi

rty m

illili

ters

of t

he h

emat

in s

tock

sol

utio

n is

add

ed to

1 L

of M

HB

with

5 g

of y

east

ext

ract

.A

fter a

utoc

lavi

ng a

nd c

oolin

g, c

atio

ns a

re a

dded

ase

ptic

ally,

if n

eede

d, a

s in

CA

MH

B, a

nd 3

mL

of N

AD

sto

ck s

olut

ion

(50

mg

of N

AD

dis

solv

ed in

10

mL

ofdi

still

ed w

ater

; filt

er s

teril

ized

) is

also

add

ed a

sept

ical

ly. If

sul

fona

mid

es o

r trim

etho

prim

are

to b

e te

sted

, 0.2

IU/m

Lth

ymid

ine

phos

phor

ylas

e sh

ould

als

o be

adde

d to

the

med

ium

ase

ptic

ally.

(4)

For s

ome

orga

nism

/ant

imic

robi

al a

gent

com

bina

tions

, the

abs

ence

of r

esis

tant

stra

ins

prec

lude

s de

finin

g an

y re

sults

cat

egor

ies

othe

r tha

n “s

usce

ptib

le.”

For

stra

ins

yiel

ding

res

ults

sug

gest

ive

of a

“no

nsus

cept

ible

” ca

tego

ry,

orga

nism

iden

tific

atio

n an

d an

timic

robi

al s

usce

ptib

ility

tes

t re

sults

sho

uld

be c

onfir

med

.S

ubse

quen

tly, t

he is

olat

es s

houl

d be

sav

ed a

nd s

ubm

itted

to a

refe

renc

e la

bora

tory

that

will

con

firm

resu

lts u

sing

a C

LSI/N

CC

LS re

fere

nce

dilu

tion

met

hod.

NO

TE:

Info

rmat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.


121

Tabl

e 2E

Hae

mop

hilu

sspp

.M

7-M

IC


Tabl

e 2E

. (C

ontin

ued)

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

Rββ -

LAC

TAM

/ββ-L

AC

TAM

ASE

INH

IBIT

OR

CO

MB

INAT

ION

SS

ee c

omm

ent (

6).

BA

mpi

cilli

n-su

lbac

tam

≤2/

1-

≥4/

2C

Am

oxic

illin

-cla

vula

nic

acid

≤4/

2 -

≥8/

4O

Pip

erac

illin

-tazo

bact

am≤

1/4

- ≥

2/4

CEP

HEM

S (P

AR

ENTE

RA

L) (

Incl

udin

g ce

phal

ospo

rins

I, II,

III,

and

IV. P

leas

e re

fer

to G

loss

ary

I.)

See

com

men

t (6)

.

B B B B

Cef

otax

ime

or

cefta

zidi

me

orce

ftizo

xim

e or

ce

ftria

xone

≤2

≤2

≤2

≤2

- - - -

- - - -

See

com

men

t (4)

.

BC

efur

oxim

e so

dium

(par

ente

ral)

≤4

8≥

16C

Cef

onic

id≤

48

≥16

OC

efam

ando

le≤

48

≥16

OC

efep

ime

≤2

--

See

com

men

t (4)

.C

EPH

EMS

(OR

AL)

C C C

Cef

aclo

r or

cefp

rozi

l or

lora

carb

ef

≤8

≤8

≤8

16 16 16

≥32

≥32

≥32

C C C

Cef

dini

r or

cefix

ime

orce

fpod

oxim

e

≤1

≤1

≤2

- - -

- - -

See

com

men

t (4)

.

CC

efur

oxim

e ax

etil

(ora

l)≤

48

≥16

OC

eftib

uten

≤2

--

See

com

men

t (4)

.In

v.C

efet

amet

≤4

8≥

16C

AR

BA

PEN

EMS

BM

erop

enem

≤0.

5-

-S

ee c

omm

ent (

4).

C CE

rtape

nem

or

imip

enem

≤0.

5≤

4- -

- -S

ee c

omm

ent (

4).

MO

NO

BA

CTA

MS

CA

ztre

onam

≤2

--

See

com

men

t (4)

.M

AC

RO

LID

ESC C

Azi

thro

myc

in o

rcl

arith

rom

ycin

≤4

≤8

- 16-

≥32

See

com

men

t (4)

.

KET

OLI

DES

CTe

lithr

omyc

in≤≤

48

≥16

TETR

AC

YCLI

NES

CTe

tracy

clin

e≤

24

≥8

(7)

Org

anis

ms

that

are

sus

cept

ible

to te

tracy

clin

e ar

e al

so c

onsi

dere

dsu

scep

tible

to d

oxyc

yclin

e an

d m

inoc

yclin

e.


122

Tabl

e 2E

Hae

mop

hilu

sspp

.M

7-M

IC

Tabl

e 2E

. (C

ontin

ued)

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

RFL

UO

RO

QU

INO

LON

ESC

C C C C C C

Cip

roflo

xaci

n or

gatif

loxa

cin

orle

voflo

xaci

n or

lom

eflo

xaci

n or

mox

iflox

acin

or

oflo

xaci

n or

spar

floxa

cin

≤1

≤1

≤2

≤2

≤1

≤2

≤0.

25

- - - - - - -

- - - - - - -

See

com

men

t (4)

CG

emifl

oxac

in≤

0.12

--

OG

repa

floxa

cin

≤0.

5-

-O

Trov

aflo

xaci

n≤

1-

-In

v.Fl

erox

acin

≤2

--

FOLA

TE P

ATH

WAY

INH

IBIT

OR

SA

Trim

etho

prim

-sul

fam

etho

xazo

le≤

0.5/

9.5

1/19

-2/3

8≥

4/76

PHEN

ICO

LSB

Chl

oram

phen

icol

≤2

4≥

8A

NSA

MYC

INS

CR

ifam

pin

≤1

2≥

4



124

Tabl

e 2F

Nei

sser

ia g

onor

rhoe

aeM

7-M

IC


Tabl

e 2F

. M

IC In

terp

retiv

e St

anda

rds

(µµg/

mL)

for

Nei

sser

ia g

onor

rhoe

ae

Min

imal

QC

Rec

omm

enda

tions

(See

Tab

le 3

Afo

r ac

cept

able

QC

rang

es.)

Nei

sser

ia g

onor

rhoe

aeAT

CC

®49

226

Test

ing

Con

ditio

ns

Med

ium

:A

gar d

ilutio

n: G

C a

gar b

ase

and

1% d

efin

ed g

row

th s

uppl

emen

t. Th

e us

e of

a cy

stei

ne-fr

ee

supp

lem

ent

is

requ

ired

for

agar

di

lutio

n te

sts

with

carb

apen

ems

and

clav

ulan

ate.

C

yste

ine-

cont

aini

ng

defin

ed

grow

thsu

pple

men

ts d

o no

tsig

nific

antly

alte

r dilu

tion

test

resu

lts w

ith o

ther

dru

gs.

Inoc

ulum

:D

irect

col

ony

susp

ensi

on, e

quiv

alen

t to

a 0.

5 M

cFar

land

sta

ndar

dIn

cuba

tion:

35 °

C ±

2 de

gree

s; 5

% C

O2;

20

to 2

4 ho

urs

Gen

eral

Com

men

ts

(1)

The

reco

mm

ende

d m

ediu

m fo

r te

stin

g N

. gon

orrh

oeae

cons

ists

of G

C a

gar

to w

hich

a 1

% d

efin

ed g

row

th s

uppl

emen

t (1.

1 g

L-cy

stei

ne, 0

.03

g gu

anin

eH

CL,

3 m

g th

iam

ine

HC

L, 1

3 m

g PA

BA

, 0.0

1 g

B12

, 0.1

g c

ocar

boxy

lase

, 0.2

5 g

NA

D, 1

g a

deni

ne, 1

0 g

L-gl

utam

ine,

100

g g

luco

se, 0

.02

g fe

rric

nitr

ate

[in 1

LH

2O])

is a

dded

afte

r aut

ocla

ving

.

(2)

For s

ome

orga

nism

/ant

imic

robi

al a

gent

com

bina

tions

, the

abs

ence

of r

esis

tant

stra

ins

prec

lude

s de

finin

g an

y re

sults

cat

egor

ies

othe

r tha

n “s

usce

ptib

le.”

For

stra

ins

yiel

ding

resu

lts s

ugge

stiv

e of

a “n

onsu

scep

tible

” cat

egor

y, o

rgan

ism

iden

tific

atio

n an

d an

timic

robi

al s

usce

ptib

ility

test

resu

lts s

houl

d be

con

firm

ed. S

ubse

quen

tly, t

heis

olat

es s

houl

d be

sav

ed a

nd s

ubm

itted

to a

refe

renc

e la

bora

tory

that

will

con

firm

resu

lts u

sing

a C

LSI/N

CC

LS re

fere

nce

dilu

tion

met

hod.

NO

TE:

Info

rmat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.


125

Tabl

e 2F

Nei

sser

ia g

onor

rhoe

aeM

7-M

IC


Tabl

e 2F

. (C

ontin

ued)

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

RPE

NIC

ILLI

NS

CP

enic

illin

≤0.

060.

12-1

≥2

(3)

Apo

sitiv

e β-

lact

amas

e te

st p

redi

cts

resi

stan

ce to

pen

icill

in, a

mpi

cilli

n, a

ndam

oxic

illin

.

(4)

Aβ-

lact

amas

e te

st w

ill d

etec

t on

e fo

rm o

f pe

nici

llin

resi

stan

ce i

n N

.go

norrh

oeae

and

also

may

be

used

to

prov

ide

epid

emio

logi

c in

form

atio

n.St

rain

s w

ith c

hrom

osom

ally

med

iate

d re

sist

ance

can

be

dete

cted

onl

y by

the

disk

diff

usio

n m

etho

d or

the

agar

dilu

tion

MIC

met

hod.

CEP

HEM

S (P

AR

ENTE

RA

L) (

Incl

udin

g ce

phal

ospo

rins

I, II,

III,

and

IV. P

leas

e re

fer

to G

loss

ary

I.)C C C

Cef

otax

ime

orce

ftizo

xim

e or

ceftr

iaxo

ne

≤0.

5≤

0.5

≤0.

25

– – –

– – –

See

com

men

t (2)

.

C C C C

Cef

met

azol

e C

efot

etan

C

efox

itin

Cef

urox

ime

sodi

um (p

aren

tera

l)

≤2

≤2

≤2

≤1

4 4 4 2

≥8

≥8

≥8

≥4

OC

efep

ime

≤0.

5–

–S

ee c

omm

ent (

2).

OC

efta

zidi

me

≤0.

5–

–S

ee c

omm

ent (

2).

CEP

HEM

S (O

RA

L)C C

Cef

ixim

e or

ce

fpod

oxim

e≤

0.25

≤0.

5– –

– –S

ee c

omm

ent (

2).

Inv.

Cef

etam

et≤

0.5

––

See

com

men

t (2)

.TE

TRA

CYC

LIN

ESC

Tetra

cycl

ine

≤0.

250.

5-1

≥2

(5)

Org

anis

ms

that

are

sus

cept

ible

to

tetra

cycl

ine

are

also

con

side

red

susc

eptib

le to

dox

ycyc

line

and

min

ocyc

line.

FLU

OR

OQ

UIN

OLO

NES

C C C

Cip

roflo

xaci

n or

gatif

loxa

cin

orof

loxa

cin

≤0.

06≤

0.12

5≤

0.25

0.12

-0.5

0.25

0.5-

1

≥1

≥0.

5≥

2O

Eno

xaci

n≤

0.5

1≥

2O

Gre

paflo

xaci

n≤

0.06

0.

12-0

.5≥

1O

Lom

eflo

xaci

n≤

0.12

0.25

-1≥

2O

Trov

aflo

xaci

n≤

0.25

–

–S

ee c

omm

ent (

2).

Inv.

Fler

oxac

in≤

0.25

0.5

≥1

AM

INO

CYC

LITO

LS

C

Spec

tinom

ycin

≤32

64≥

128


126

Tabl

e 2G

Stre

ptoc

occu

s pne

umon

iae

M7-

MIC


Tabl

e 2G

. M

IC In

terp

retiv

e St

anda

rds

(µµg/

mL)

for

Stre

ptoc

occu

s pn

eum

onia

e

Test

ing

Con

ditio

ns

Med

ium

:B

roth

dilu

tion:

Cat

ion-

adju

sted

Mue

ller-

Hin

ton

brot

h w

ith l

ysed

hor

se b

lood

(LH

B) (

2 to

5%

v/v

)In

ocul

um:

Dire

ct c

olon

y su

spen

sion

, equ

ival

ent t

o a

0.5

McF

arla

nd s

tand

ard

Incu

batio

n:35

°C

±2

degr

ees;

am

bien

t air;

20

to 2

4 ho

urs

Min

imal

Q

C

Rec

omm

enda

tions

(See

Ta

ble

3Afo

rac

cept

able

QC

rang

es).

Stre

ptoc

occu

s pn

eum

onia

eAT

CC

®49

619

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

RPE

NIC

ILLI

NS

(4)

Apn

eum

ococ

cal

isol

ate

that

is

susc

eptib

le t

o pe

nici

llin

can

beco

nsid

ered

sus

cept

ible

to

ampi

cilli

n, a

mox

icill

in,

amox

icill

in-c

lavu

lani

cac

id,

ampi

cilli

n-su

lbac

tam

, ce

facl

or,

cefd

inir,

ce

fepi

me,

ce

feta

met

,ce

fixim

e,

cefo

taxi

me,

ce

fpro

zil,

cefti

bute

n,

ceftr

iaxo

ne,

cefu

roxi

me,

cefp

odox

ime,

ce

ftizo

xim

e,

erta

pene

m,

imip

enem

, lo

raca

rbef

, an

dm

erop

enem

for

app

rove

d in

dica

tions

. Te

stin

g of

am

pici

llin,

am

pici

llin-

sulb

acta

m,

cefti

bute

n,

cefe

tam

et,

cefti

zoxi

me,

an

d ce

fixim

e ag

ains

tpe

nici

llin-

inte

rmed

iate

or p

enic

illin

-res

ista

nt is

olat

es is

not

reco

mm

ende

d,be

caus

e re

liabl

e in

terp

retiv

e cr

iteria

for t

hose

age

nts

with

S. p

neum

onia

ear

e no

t av

aila

ble.

Phy

sici

ans

shou

ld b

e in

form

ed t

hat

clin

ical

res

pons

era

tes

with

thes

e ag

ents

may

be

low

er in

stra

ins

that

are

not

sus

cept

ible

tope

nici

llin.

See

com

men

t (1

).A

Pen

icill

in≤

0.06

0.12

-1≥

2(5

) R

x:H

igh

dose

s of

intra

veno

us p

enic

illin

s (e

.g.,

at le

ast 2

mill

ion

units

ever

y fo

ur h

ours

in a

dults

with

nor

mal

rena

l fun

ctio

n) o

r sim

ilarly

am

pici

llin

are

effe

ctiv

e in

tre

atin

g pn

eum

ococ

cal p

neum

onia

due

to

stra

ins

in t

hein

term

edia

te c

ateg

ory.

C CA

mox

icill

in (n

onm

enin

gitis

) or

amox

icill

in-c

lavu

lani

c ac

id

(non

men

ingi

tis)

≤2

≤2/

14 4/

2≥

8≥

8/4

Gen

eral

Com

men

ts

(1)

Onl

y re

sults

of t

estin

g w

ith p

enic

illin

, cef

otax

ime,

cef

triax

one,

mer

open

em, a

nd v

anco

myc

in s

houl

d be

repo

rted

rout

inel

y fo

r CS

F is

olat

es o

f S. p

neum

onia

e.

(2)

Inst

ruct

ions

for

pre

para

tion

of ly

sed

hors

e bl

ood

are

prov

ided

in C

LSI/N

CC

LS d

ocum

ent

M7—

Met

hods

for

Dilu

tion

Antim

icro

bial

Sus

cept

ibilit

y Te

sts

for

Bact

eria

That

Gro

w A

erob

ical

ly.

(3)

For s

ome

orga

nism

/ant

imic

robi

al a

gent

com

bina

tions

, the

abs

ence

of r

esis

tant

stra

ins

prec

lude

s de

finin

g an

y re

sults

cat

egor

ies

othe

r tha

n “s

usce

ptib

le.”

For

stra

ins

yiel

ding

res

ults

sug

gest

ive

of a

“no

nsus

cept

ible

” ca

tego

ry, o

rgan

ism

iden

tific

atio

n an

d an

timic

robi

al s

usce

ptib

ility

test

res

ults

sho

uld

be c

onfir

med

.S

ubse

quen

tly, t

he is

olat

es s

houl

d be

sav

ed a

nd s

ubm

itted

to a

refe

renc

e la

bora

tory

that

will

con

firm

resu

lts u

sing

a C

LSI/N

CC

LS re

fere

nce

dilu

tion

met

hod .

NO

TE:

Info

rmat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.


127

Tabl

e 2G

Stre

ptoc

occu

s pne

umon

iae

M7-

MIC


Tabl

e 2G

. (C

ontin

ued)

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rd

Com

men

ts

SI

RC

EPH

EMS

(PA

REN

TER

AL)

(In

clud

ing

ceph

alos

porin

s I,

II, II

I, an

d IV

. Ple

ase

refe

r to

Glo

ssar

y I.)

See

com

men

t (1)

.B

Cef

epim

e (n

onm

enin

gitis

)≤

12

≥4

(6)

Onl

y re

port

inte

rpre

tatio

ns fo

r non

men

ingi

tis a

nd in

clud

e th

e no

nmen

ingi

tis n

otat

ion

on th

e re

port.

The

re is

not

a U

.S. F

DA

-app

rove

d in

dica

tion

for

the

use

of c

efep

ime

for

men

ingi

tis.

B

Cef

epim

e (m

enin

gitis

)≤

0.5

1 ≥

2B B

Cef

otax

ime

(men

ingi

tis) o

rce

ftria

xone

(men

ingi

tis)

≤0.

5≤

0.5

1 1≥

2≥

2(7

) Fo

r CS

F is

olat

es, r

epor

t onl

y m

enin

gitis

inte

rpre

tatio

ns.

(8)

Rx:

Use

of c

efot

axim

e or

cef

triax

one

in m

enin

gitis

req

uire

s th

erap

y w

ith m

axim

umdo

ses.

B BC

efot

axim

e (n

onm

enin

gitis

) or

ceftr

iaxo

ne (n

onm

enin

gitis

)≤

1≤

12 2

≥4

≥4

(9)

For a

ll is

olat

es o

ther

than

thos

e fro

m C

SF,

repo

rt in

terp

reta

tions

for b

oth

men

ingi

tisan

d no

nmen

ingi

tis.

(10)

Rx:

For

cefo

taxi

me,

use

of

inte

rpre

tive

crite

ria f

or n

onm

enin

gitis

req

uire

s do

ses

appr

opria

te fo

r se

rious

pne

umoc

occa

l inf

ectio

ns (

e.g.

, at l

east

1 g

[adu

lts] o

r 50

mg/

kg[c

hild

ren]

eve

ry e

ight

hou

rs o

r mor

e fre

quen

tly).

C

Cef

urox

ime

sodi

um (p

aren

tera

l)≤

0.5

1 ≥

2C

EPH

EMS

(OR

AL)

OC

efac

lor

≤1

2 ≥

4O

Cef

dini

r≤

0.5

1 ≥

2O

Cef

podo

xim

e≤

0.5

1 ≥

2O

C

efpr

ozil

≤2

4 ≥

8O

C

efur

oxim

e ax

etil

(ora

l)≤

12

≥4

OLo

raca

rbef

≤

24

≥8

CA

RB

APE

NEM

SS

ee c

omm

ent (

1).

BM

erop

enem

≤0.

250.

5≥

1C

Erta

pene

m≤

12

≥4

CIm

ipen

em≤

0.12

0.25

-0.5

≥1

GLY

CO

PEPT

IDES

See

com

men

t (1)

.B

Vanc

omyc

in≤

1-

- S

ee c

omm

ent (

3).

MA

CR

OLI

DES

(11)

Sus

cept

ibili

ty a

nd re

sist

ance

to a

zith

rom

ycin

, cla

rithr

omyc

in, a

nd d

irith

rom

ycin

can

be p

redi

cted

by

usin

g er

ythr

omyc

in.

(12)

Not

rout

inel

y re

porte

d on

isol

ates

from

the

urin

ary

tract

.A

Ery

thro

myc

in

≤0.

250.

5≥

1O

A

zith

rom

ycin

≤0.

51

≥2

O

Cla

rithr

omyc

in≤

0.25

0.5

≥1

OD

irith

rom

ycin

≤0.

51

≥2

KET

OLI

DES

BTe

lithr

omyc

in≤

12

≥4

TETR

AC

YCLI

NES

BTe

tracy

clin

e ≤

24

≥8

(13)

O

rgan

ism

s th

at a

re s

usce

ptib

le to

tetra

cycl

ine

are

also

con

side

red

susc

eptib

le to

doxy

cycl

ine

and

min

ocyc

line.


128

Tabl

e 2G

Stre

ptoc

occu

s pne

umon

iae

M7-

MIC


Tabl

e 2G

. (C

ontin

ued)

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rd

Com

men

ts

SI

RFL

UO

RO

QU

INO

LON

ESB B B B B

B

Gat

iflox

acin

G

emifl

oxac

in

Levo

floxa

cin

Mox

iflox

acin

Spar

floxa

cin

Oflo

xaci

n

≤1

≤0.

12≤

2≤

1≤

0.5

≤2

20.

25

4 2 1 4

≥4

≥0.

5≥

8≥

4≥

2≥

8O

Gre

paflo

xaci

n≤

0.5

1≥

2O

Trov

aflo

xaci

n≤

12

≥4

FOLA

TE P

ATH

WAY

INH

IBIT

OR

SA

Trim

etho

prim

-sul

fam

etho

xazo

le≤

0.5/

9.5

1/19

-2/3

8≥

4/76

PHEN

ICO

LSC

Chl

oram

phen

icol

≤4

-≥

8S

ee c

omm

ent (

12).

AN

SAM

YCIN

SC

Rifa

mpi

n≤

12

≥4

(14)

Rx:

Rifa

mpi

n sh

ould

not

be

used

alo

ne fo

r che

mot

hera

py.

LIN

CO

SAM

IDES

BC

linda

myc

in≤

0.25

0.5

≥1

See

com

men

t (12

).ST

REP

TOG

RA

MIN

SO

Qui

nupr

istin

-dal

fopr

istin

≤1

2≥

4O

XAZO

LID

INO

NES

CLi

nezo

lid≤

2-

-S

ee c

omm

ent (

3).


130

Tabl

e 2H

Stre

ptoc

occu

sspp

. O

ther

Tha

n S.

pne

umon

iae

M7-

MIC


Tabl

e 2H

. M

IC In

terp

retiv

e St

anda

rds

(µµg/

mL)

for

Stre

ptoc

occu

ssp

p. O

ther

Tha

n St

rept

ococ

cus

pneu

mon

iae

Min

imal

QC

Rec

omm

enda

tions

(See

Tab

le 3

Afo

rac

cept

able

QC

rang

es.)

Stre

ptoc

occu

s pn

eum

onia

eAT

CC

®49

619

Test

ing

Con

ditio

ns

Med

ium

:B

roth

dilu

tion:

Cat

ion-

adju

sted

Mue

ller-

Hin

ton

brot

h w

ith ly

sed

hors

e bl

ood

(2 to

5%

v/v

); C

AM

HB

sup

plem

ente

d to

50

µµ g/m

Lca

lciu

m fo

r da

ptom

ycin

Aga

r dilu

tion:

Mue

ller-

Hin

ton

with

she

ep b

lood

(5%

v/v

) (w

hen

test

ing

asu

lfona

mid

e, ly

sed

hors

e bl

ood

shou

ld b

e us

ed);

agar

dilu

tion

is

curr

ently

not

rec

omm

ende

d fo

r da

ptom

ycin

. In

ocul

um:

Dire

ct c

olon

y su

spen

sion

, equ

ival

ent t

o a

0.5

McF

arla

nd s

tand

ard

Incu

batio

n:35

°C

±2

degr

ees;

am

bien

t air;

20

to 2

4 ho

urs

(CO

2if

nece

ssar

y fo

rgr

owth

with

aga

r dilu

tion)

Gen

eral

Com

men

ts

(1)

For

this

tabl

e, th

e be

ta-h

emol

ytic

gro

up in

clud

es th

e la

rge-

colo

ny-fo

rmin

g py

ogen

ic s

train

s of

stre

ptoc

occi

with

Gro

up A

(S. p

yoge

nes)

, C, o

r G a

ntig

ens

and

stra

ins

with

Gro

up B

(S. a

gala

ctia

e)an

tigen

. Sm

all-c

olon

y-fo

rmin

g be

ta-h

emol

ytic

stra

ins

with

Gro

up A

, C, F

, or G

ant

igen

s (S

. ang

inos

us, p

revi

ousl

y te

rmed

“S. m

illeri”

) are

con

side

red

part

of th

e vi

ridan

s gr

oup,

and

inte

rpre

tive

crite

ria fo

r the

viri

dans

gro

up s

houl

d be

use

d. T

he v

irida

ns g

roup

als

o in

clud

es S

. miti

s, S

. ora

lis, S

. san

guis

, S. s

aliv

ariu

s, S

. int

erm

ediu

s, S

. con

stel

latu

s, S

. mut

ans,

and

S. b

ovis

.

(2)

Sus

cept

ibili

ty te

stin

g of

pen

icill

ins

and

othe

r β-la

ctam

s ap

prov

ed b

y th

e FD

Afo

r tre

atm

ent o

f Gro

up A

and

Gro

up B

stre

ptoc

occi

is n

ot n

eces

sary

for c

linic

al p

urpo

ses

and

need

not

be

done

rout

inel

y, s

ince

as

with

van

com

ycin

, res

ista

nt s

train

s ha

ve n

ot b

een

reco

gniz

ed. B

reak

poin

ts a

nd in

terp

retiv

e cr

iteria

are

pro

vide

d fo

r pha

rmac

eutic

al d

evel

opm

ent,

epid

emio

logy

, or m

onito

ring

for e

mer

ging

resi

stan

ce. A

ny s

train

s fo

und

to b

e no

nsus

cept

ible

sho

uld

be re

ferr

ed to

a re

fere

nce

labo

rato

ry fo

r con

firm

atio

n.

(3)

Inte

rpre

tive

crite

ria fo

r st

rept

ococ

ci o

ther

than

S. p

neum

onia

ear

e pr

opos

ed b

ased

on

popu

latio

n di

strib

utio

ns o

f var

ious

spe

cies

, pha

rmac

okin

etic

s of

the

antim

icro

bial

age

nts,

pre

viou

sly

publ

ishe

d lit

erat

ure,

and

the

clin

ical

exp

erie

nce

of c

erta

in m

embe

rs o

f the

sub

com

mitt

ee. S

yste

mat

ical

ly c

olle

cted

clin

ical

dat

a w

ere

not a

vaila

ble

for r

evie

w w

ith m

any

of th

e co

mpo

unds

inth

e gr

oup.

(4)

Inst

ruct

ions

for p

repa

ratio

n of

lyse

d ho

rse

bloo

d ar

e pr

ovid

ed in

CLS

I/NC

CLS

doc

umen

t M7—

Met

hods

for D

ilutio

n An

timic

robi

al S

usce

ptib

ility

Test

s fo

r Bac

teria

Tha

t Gro

w A

erob

ical

ly.

(5)

For s

ome

orga

nism

/ant

imic

robi

al a

gent

com

bina

tions

, the

abs

ence

of r

esis

tant

stra

ins

prec

lude

s de

finin

g an

y re

sults

cat

egor

ies

othe

r tha

n “s

usce

ptib

le.”

For

stra

ins

yiel

ding

resu

lts s

ugge

stiv

eof

a “

nons

usce

ptib

le”

cate

gory

, or

gani

sm id

entif

icat

ion

and

antim

icro

bial

sus

cept

ibili

ty t

est

resu

lts s

houl

d be

con

firm

ed.

Sub

sequ

ently

, th

e is

olat

es s

houl

d be

sav

ed a

nd s

ubm

itted

to

are

fere

nce

labo

rato

ry th

at w

ill c

onfir

m re

sults

usi

ng a

CLS

I/NC

CLS

refe

renc

e di

lutio

n m

etho

d.

NO

TE:

Info

rmat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

RPE

NIC

ILLI

NS

(6)

Ast

rept

ococ

cal i

sola

te th

at is

sus

cept

ible

to p

enic

illin

can

be

cons

ider

edsu

scep

tible

to

ampi

cilli

n, a

mox

icill

in,

amox

icill

in-c

lavu

lani

c ac

id,

ampi

cilli

n-su

lbac

tam

, ce

facl

or,

cefa

zolin

, ce

fdin

ir,

cefe

pim

e,

cefp

rozi

l, ce

fota

xim

e,ce

ftibu

ten

(Gro

up A

stre

ptoc

occi

onl

y), c

eftri

axon

e, c

efur

oxim

e, c

efpo

doxi

me,

cefti

zoxi

me,

ce

phra

dine

, ce

phal

othi

n,

ceph

apiri

n,

erta

pene

m,

imip

enem

,lo

raca

rbef

, and

mer

open

em fo

r ap

prov

ed in

dica

tions

, and

nee

d no

t be

test

edag

ains

t tho

se a

gent

s.A A

Pen

icill

in (b

eta-

hem

olyt

ic g

roup

) or

ampi

cilli

n (b

eta-

hem

olyt

ic g

roup

)≤

0.12

≤0.

25- -

- -S

ee c

omm

ent (

5).

(7)

Stra

ins

of b

eta-

hem

olyt

ic s

trept

ococ

ci w

ith p

enic

illin

MIC

s of

gre

ater

than

0.12

µg/

mL

or a

mpi

cilli

n M

ICs

of g

reat

er t

han

0.25

µg/

mL

have

not

bee

nob

serv

ed; s

ubm

it su

ch s

train

s to

a re

fere

nce

labo

rato

ry.



Tabl

e 2H

Stre

ptoc

occu

sspp

. O

ther

Tha

nS.

pne

umon

iae

M7-

MIC

Tabl

e 2H

. (C

ontin

ued)

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

RPE

NIC

ILLI

NS

(Con

tinue

d)A A

Pen

icill

in (v

irida

ns g

roup

) or

ampi

cilli

n (v

irida

ns g

roup

) ≤

0.12

≤0.

250.

25-2

0.5-

4 ≥

4≥

8(8

) R

x:P

enic

illin

- or

am

pici

llin-

inte

rmed

iate

iso

late

s m

ay r

equi

re c

ombi

ned

ther

apy

with

an

amin

ogly

cosi

de fo

r bac

teric

idal

act

ion.

CEP

HEM

S (P

AR

ENTE

RA

L) (I

nclu

ding

cep

halo

spor

ins

I, II,

III,

and

IV. P

leas

e re

fer

to G

loss

ary

I.)S

ee c

omm

ent (

6).

C C C C C

C

Cef

epim

e (b

eta-

hem

olyt

ic g

roup

) or

cefo

taxi

me

(bet

a-he

mol

ytic

gro

up) o

rce

ftria

xone

(bet

a-he

mol

ytic

gro

up)

Cef

epim

e (v

irida

ns g

roup

) or

cefo

taxi

me

(viri

dans

gro

up) o

rce

ftria

xone

(viri

dans

gro

up)

≤0.

5≤

0.5

≤0.

5

≤1

≤1

≤1

- - - 2 2 2

- - - ≥4

≥4

≥4

See

com

men

t (5)

.

CA

RB

APE

NEM

SO

Erta

pene

m≤

1

--

(9) B

reak

poin

ts a

re fo

r rep

ortin

g ag

ains

t bet

a-he

mol

ytic

stre

ptoc

occi

onl

y.

See

com

men

t (5)

.O

Mer

open

em≤

0.5

--

See

com

men

t (5)

.G

LYC

OPE

PTID

ESB

Vanc

omyc

in≤

1-

- S

ee c

omm

ent (

5).

LIPO

PEPT

IDES

CD

apto

myc

in≤≤

1

--

See

com

men

t (5)

.M

AC

RO

LID

ES(1

0)

S

usce

ptib

ility

an

d re

sist

ance

to

az

ithro

myc

in,

clar

ithro

myc

in,

and

dirit

hrom

ycin

can

be

pred

icte

d by

test

ing

eryt

hrom

ycin

.

(11)

Not

rout

inel

y re

porte

d on

isol

ates

from

the

urin

ary

tract

.A

Ery

thro

myc

in≤

0.25

0.5

≥1

(12)

Rx:

Rec

omm

enda

tions

for

int

rapa

rtum

pro

phyl

axis

for

Gro

up B

stre

ptoc

occi

are

pen

icill

in o

r am

pici

llin.

Whi

le c

efaz

olin

is r

ecom

men

ded

for p

enic

illin

-alle

rgic

wom

en a

t low

risk

for a

naph

ylax

is, t

hose

at h

igh

risk

for

anap

hyla

xis

may

re

ceiv

e cl

inda

myc

in

or

erth

rom

ycin

. G

roup

B

stre

ptoc

occi

are

sus

cept

ible

to

ampi

cilli

n, p

enic

illin

, an

d ce

fazo

lin,

but

may

be

resi

stan

t to

clin

dam

ycin

and

/or

eryt

hrom

ycin

. W

hen

a gr

oup

Bst

rept

ococ

cus

is i

sola

ted

from

a p

regn

ant

wom

an w

ith s

ever

e pe

nici

llin

alle

rgy

(hig

h ris

k fo

r an

aphy

laxi

s), c

linda

myc

in a

nd e

ryth

rom

ycin

sho

uld

be te

sted

and

rep

orte

d.O

Azi

thro

myc

in≤

0.5

1 ≥

2O

Cla

rithr

omyc

in≤

0.25

0.5

≥1

OD

irith

rom

ycin

≤0.

51

≥2

TETR

AC

YCLI

NES

OTe

tracy

clin

e ≤

24

≥8

(13)

Org

anis

ms

that

ar

e su

scep

tible

to

te

tracy

clin

e ar

e al

so

cons

ider

edsu

scep

tible

to d

oxyc

yclin

e an

d m

inoc

yclin

e.



Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

RFL

UO

RO

QU

INO

LON

ESC

Levo

floxa

cin

≤2

4≥

8C

Oflo

xaci

n≤

2 4

≥8

See

com

men

t (9)

.O

Gat

iflox

acin

≤1

2≥

4 S

ee c

omm

ent (

9).

OG

repa

floxa

cin

≤0.

51

≥2

OTr

ovaf

loxa

cin

≤1

2≥

4PH

ENIC

OLS

BC

hlor

amph

enic

ol≤

48

≥16

See

com

men

t (11

).LI

NC

OSA

MID

ESB

Clin

dam

ycin

≤0.

250.

5≥

1S

ee c

omm

ents

(11)

and

(12)

.(1

4) M

acro

lide-

resi

stan

t is

olat

es o

f be

ta-h

emol

ytic

str

epto

cocc

i m

ay h

ave

cons

titut

ive

or in

duci

ble

resi

stan

ce to

clin

dam

ycin

[met

hyla

tion

of th

e 23

SrR

NA

enco

ded

by a

n er

mge

ne a

lso

refe

rred

to

as M

LSB

(mac

rolid

e,lin

cosa

mid

e, a

nd ty

pe B

str

epto

gram

in) r

esis

tanc

e] o

r may

be

resi

stan

t onl

yto

mac

rolid

es (

efflu

x m

echa

nism

enc

oded

by

a m

efge

ne).

Indu

cibl

ecl

inda

myc

in re

sist

ance

can

be

dete

cted

usi

ng a

dis

k ap

prox

imat

ion

test

by

plac

ing

a 2-

µµ g

clin

dam

ycin

di

sk

12

mm

fr

om

the

edge

of

a

15-µµ

ger

ythr

omyc

in d

isk

as p

art o

f the

nor

mal

dis

k di

ffusi

on p

roce

dure

. Fol

low

ing

incu

batio

n, o

rgan

ism

s th

at d

o no

t sho

w fl

atte

ning

of t

he c

linda

myc

in z

one

shou

ld b

e re

port

ed a

s cl

inda

myc

in s

usce

ptib

le.

Org

anis

ms

that

sho

wfla

tteni

ng o

f th

e cl

inda

myc

in z

one

adja

cent

to

the

eryt

hrom

ycin

dis

k(r

efer

red

to a

s a

“D”

zone

) ha

ve i

nduc

ible

clin

dam

ycin

res

ista

nce.

Su

chis

olat

es s

houl

d be

rep

orte

d as

“cl

inda

myc

in r

esis

tant

.”

Aco

mm

ent

that

"Thi

s is

olat

e is

pre

sum

ed t

o be

res

ista

nt b

ased

on

dete

ctio

n of

indu

cibl

ecl

inda

myc

in

resi

stan

ce.

C

linda

myc

in

may

st

ill

be

effe

ctiv

e in

so

me

patie

nts.

" m

ay b

e in

clud

ed.

STR

EPTO

GR

AM

INS

CQ

uinu

pris

tin-d

alfo

pris

tin

≤1

2≥

4(1

5) R

epor

t aga

inst

Stre

ptoc

occu

s py

ogen

es.

OXA

ZOLI

DIN

ON

ESC

Line

zolid

≤2

--

See

com

men

t (5)

.

Tabl

e 2H

. (C

ontin

ued)

Tabl

e 2H

Stre

ptoc

occu

sspp

. O

ther

Tha

nS.

pne

umon

iae

M7-

MIC


134

Tabl

e 2I

Vibr

io c

hole

rae

M7-

MIC


Tabl

e 2I

. M

IC In

terp

retiv

e St

anda

rds

(µµg/

mL)

for

Vibr

io c

hole

rae

Test

ing

Con

ditio

ns

Med

ium

:B

roth

dilu

tion:

Cat

ion-

adju

sted

Mue

ller-

Hin

ton

brot

h (C

AM

HB

)A

gar d

ilutio

n: M

uelle

r-H

into

n ag

ar (M

HA

)In

ocul

um:

Gro

wth

met

hod

or d

irect

col

ony

susp

ensi

on, e

quiv

alen

t to

a0.

5 M

cFar

land

sta

ndar

dIn

cuba

tion:

35 °

C ±

2 de

gree

s; a

mbi

ent a

ir; 1

6 to

20

hour

s

Min

imal

QC

Rec

omm

enda

tions

(See

Tab

le 3

for a

ccep

tabl

e Q

C ra

nges

.)

Esch

eric

hia

coli

ATC

C®

2592

2

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

RPE

NIC

ILLI

NS

AA

mpi

cilli

n≤

816

≥32

(1)

Cla

ss re

pres

enta

tive

for a

mpi

cilli

n an

d am

oxic

illin

.TE

TRA

CYC

LIN

ESC

Tetra

cycl

ine

≤4

8≥

16(2

) Te

tracy

clin

e is

the

repr

esen

tativ

e fo

r all

tetra

cycl

ines

, and

the

resu

ltsca

n be

app

lied

to d

oxyc

yclin

e.O

Dox

ycyc

line

≤4

8≥

16FO

LATE

PAT

HW

AYIN

HIB

ITO

RS

BTr

imet

hopr

im-s

ulfa

met

hoxa

zole

≤2/

38-

≥4/

76C

Sul

fona

mid

es≤

256

-≥

512

(3) S

ulfis

oxaz

ole

can

be u

sed

to re

pres

ent a

ny o

f the

cur

rent

ly a

vaila

ble

sulfo

nam

ide

prep

arat

ions

.PH

ENIC

OLS

CC

hlor

amph

enic

ol≤

816

≥32

NO

TE:

Info

rmat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.


135

Tabl

e 2J

Hel

icob

acte

r pyl

ori

M7-

MIC


Tabl

e 2J

. M

IC In

terp

retiv

e St

anda

rds

(µµg/

mL)

for

Hel

icob

acte

r pyl

ori

Min

imal

QC

Rec

omm

enda

tions

(See

Tab

le 3

Afo

r acc

epta

ble

QC

rang

es.)

Hel

icob

acte

r pyl

ori A

TCC

®43

504

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µµ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

RM

AC

RO

LID

ESA

Cla

rithr

omyc

in≤

0.25

0.5

≥1.

0(1

)

Thes

e br

eakp

oint

s pr

esum

e th

at c

larit

hrom

ycin

will

be

used

in a

nFD

A-a

ppro

ved

regi

men

tha

t in

clud

es a

pro

ton-

pum

p in

hibi

tor

or a

n H

2

anta

goni

st

(thes

e tre

atm

ents

in

clud

e om

epra

zole

, la

nsop

razo

le,

orra

ntid

ine

bism

uth

citra

te).

NO

TE:I

nfor

mat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.

Test

ing

Con

ditio

ns

Med

ium

:A

gar

dilu

tion:

M

uelle

r-H

into

n ag

ar (

MH

A)

and

aged

(≥

2w

eeks

old

) she

ep b

lood

(5%

v/v

)In

ocul

um:

Asa

line

susp

ensi

on e

quiv

alen

t to

a 2.

0 M

cFar

land

sta

ndar

d(c

onta

inin

g 1

x 10

7to

1 x

108

CFU

/mL)

, to

be p

repa

red

from

a 72

-hou

r-ol

d su

bcul

ture

fro

m a

blo

od a

gar

plat

e.

The

inoc

ulum

(1 to

thre

e µL

per s

pot)

is re

plic

ated

dire

ctly

ont

o th

ean

timic

robi

al a

gent

-con

tain

ing

agar

dilu

tion

plat

es.

Incu

batio

n:35

°C

±2

degr

ees;

thr

ee d

ays;

mic

roae

robi

c at

mos

pher

epr

oduc

ed

by

a ga

s-ge

nera

ting

syst

em

suita

ble

for

cam

pylo

bact

ers.


136

Tabl

e 2K

Pote

ntia

l Age

nts

of B

iote

rror

ism

M7-

MIC

NO

TE:I

nfor

mat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for o

ne y

ear.

Tabl

e 2K

. M

IC In

terp

retiv

e St

anda

rds

(µµg/

mL)

for

Pote

ntia

l Age

nts

of B

iote

rror

ism

: Bac

illus

ant

hrac

is, Y

ersi

nia

pest

is, B

urkh

olde

ria m

alle

i, B

urkh

olde

ria p

seud

omal

lei,

and

Fran

cise

lla tu

lare

nsis


Org

anis

mG

roup

Ant

imic

robi

al A

gent

MIC

(µµg/

mL)

Inte

rpre

tive

Stan

dard

Com

men

ts

SI

RPE

NIC

ILLI

NS

B. a

nthr

acis

Pen

icill

in≤

0.12

-≥

0.25

(7) C

lass

repr

esen

tativ

e fo

r am

oxic

illin

.ββ -

LAC

TAM

/ββ-L

AC

TAM

ASE

INH

IBIT

OR

CO

MB

INAT

ION

SB.

pse

udom

alle

iA

mox

icill

in-c

lavu

lani

c ac

id≤

8/4

16/8

≥ 32

/16

Min

imal

QC

Rec

omm

enda

tions

(See

Tab

le 3

for a

ccep

tabl

e Q

C ra

nges

.)

Esch

eric

hia

coli

ATC

C®

259

22 (a

ll or

gani

sms)

Esch

eric

hia

coli

ATC

C®

3521

8 (fo

r am

oxic

illin

-cla

vula

nic

acid

and

B.

pseu

dom

alle

i)St

aphy

loco

ccus

aur

eus

ATC

C®

292

13 (f

orB.

ant

hrac

is a

nd F

. tul

aren

sis)

Pseu

dom

onas

aer

ugin

osa

ATC

C®

2785

3 (fo

rB. m

alle

i/pse

udom

alle

i and

F. tu

lare

nsis

)

Test

ing

Con

ditio

ns

Med

ium

:B

roth

dilu

tion:

Cat

ion-

adju

sted

Mue

ller-

Hin

ton

brot

h (C

AM

HB

); fo

r F.

tula

rens

isad

d 2%

def

ined

gro

wth

sup

plem

ent

Inoc

ulum

:G

row

th m

etho

d or

dire

ct c

olon

y su

spen

sion

in C

AM

HB

, equ

ival

ent t

o a

0.5

McF

arla

nd s

tand

ard;

for

F.

tula

rens

is p

repa

re i

nocu

lum

as

adi

rect

col

ony

susp

ensi

on fr

om a

cho

cola

te a

gar

plat

eIn

cuba

tion:

35 °

C ±

2 de

gree

s; a

mbi

ent a

ir; 1

6 to

20

hour

s;fo

r Y.

pes

tisin

cuba

te24

ho

urs

and

if un

acce

ptab

le

grow

th

in

the

cont

rol

wel

lre

incu

bate

an

addi

tiona

l 24

hour

s; fo

r F. t

ular

ensi

s in

cuba

te 4

8 ho

urs

Gen

eral

Com

men

ts

(1)

Extr

eme

Cau

tion:

Pub

lic h

ealth

offi

cial

s sh

ould

be

notif

ied

abou

t al

l is

olat

es p

resu

mpt

ivel

y id

entif

ied

as B

. an

thra

cis,

Y.

pest

is,

B. m

alle

i, or

B.ps

eudo

mal

leio

r F.

tul

aren

sis.

Con

firm

atio

n of

isol

ates

of

thes

e ba

cter

ia m

ay r

equi

re s

peci

aliz

ed t

estin

g on

ly a

vaila

ble

in r

efer

ence

or

publ

ic h

ealth

labo

rato

ries.

Rec

omm

ende

d pr

ecau

tions

: Bio

safe

ty L

evel

2 (B

SL2

) pra

ctic

es, c

onta

inm

ent e

quip

men

t, an

d fa

cilit

ies

are

reco

mm

ende

d fo

r act

iviti

es u

sing

clin

ical

mat

eria

ls a

nd d

iagn

ostic

qua

ntiti

es o

f in

fect

ious

cul

ture

s. B

iosa

fety

Lev

el 3

(B

SL3

) pr

actic

es,

cont

ainm

ent

equi

pmen

t, an

d fa

cilit

ies

are

reco

mm

ende

d fo

r wor

k in

volv

ing

prod

uctio

n qu

antit

ies

or c

once

ntra

tions

of c

ultu

res,

and

for a

ctiv

ities

with

a h

igh

pote

ntia

l for

aer

osol

pro

duct

ion.

If B

SL2

or B

SL3

faci

litie

s ar

e no

t ava

ilabl

e, is

olat

es s

houl

d be

forw

arde

d to

refe

renc

e or

pub

lic h

ealth

labo

rato

ries

for s

usce

ptib

ility

test

ing.

(2

) In

terp

retiv

e cr

iteria

are

pro

pose

d ba

sed

on p

opul

atio

n di

strib

utio

ns, p

harm

acok

inet

ics

of th

e an

timic

robi

al a

gent

s, p

revi

ousl

y pu

blis

hed

lite

ratu

re, a

ndan

imal

mod

el d

ata.

(3)

Crit

eria

forB

. ant

hrac

isdo

not

app

ly to

oth

er B

acillu

ssp

p.(4

) W

AR

NIN

G: F

or Y

. pes

tis,s

tudi

es h

ave

dem

onst

rate

d th

at a

lthou

gh β

-lact

am a

ntim

icro

bial

age

nts

may

app

ear a

ctiv

e in

vitr

o,th

ey la

ck e

ffica

cy in

ani

mal

mod

els

of in

fect

ion.

The

se a

ntim

icro

bial

age

nts

shou

ld n

ot b

e re

porte

d as

sus

cept

ible

.(5

) Th

e re

com

men

ded

med

ium

for t

estin

g F.

tula

rens

isco

nsis

ts o

f CA

MH

B to

whi

ch a

2%

def

ined

gro

wth

sup

plem

ent (

25.9

g L

-cys

tein

e H

CL,

1.1

g L-

Cys

tine,

1 g

ade

nine

, 0.0

3 g

guan

ine

HC

L, 0

.01

g Vi

tam

in B

12, 0

.1 g

coc

arbo

xyla

se, 0

.25

g N

AD

, 10

g L-

glut

amin

e, 0

.02

g fe

rric

nitr

ate,

100

g gl

ucos

e, 3

mg

thia

min

e H

CL,

13

mg

p-am

inob

enzo

ic a

cid

[in 1

LH

2O])

is a

dded

afte

r aut

ocla

ving

. The

pH

of m

ediu

m s

houl

d be

adj

uste

d to

7.2

to 7

.4.

(6)

For

som

e or

gani

sm/a

ntim

icro

bial

age

nt c

ombi

natio

ns, t

he a

bsen

ce o

f res

ista

nt s

trai

ns p

recl

udes

def

inin

g an

y re

sults

cat

egor

ies

othe

r th

an"s

usce

ptib

le."

For

str

ains

yie

ldin

g re

sults

sug

gest

ive

of a

"no

nsus

cept

ible

" ca

tego

ry, o

rgan

ism

iden

tific

atio

n an

d an

timic

robi

al s

usce

ptib

ility

test

resu

lts s

houl

d be

con

firm

ed. S

ubse

quen

tly, t

he is

olat

es s

houl

d be

sav

ed a

nd s

ubm

itted

to a

refe

renc

e la

bora

tory

that

will

con

firm

resu

ltsus

ing

a C

LSI/N

CC

LS r

efer

ence

dilu

tion

met

hod.



Tabl

e 2K

Pote

ntia

l Age

nts

of B

iote

rror

ism

M7-

MIC

Org

anis

mG

roup

Ant

imic

robi

al A

gent

MIC

(µµg/

mL)

Inte

rpre

tive

Stan

dard

Com

men

ts

SI

RC

EPH

EMS

(PA

REN

TER

AL)

(Inc

ludi

ng c

epha

losp

orin

s I,

II, II

I, an

d IV

. Ple

ase

refe

r to

Glo

ssar

y I.)

B. m

alle

i B.

pse

udom

alle

iC

efta

zidi

me

≤8

16≥

32

CA

RB

APE

NEM

S B.

mal

lei

B. p

seud

omal

lei

Imip

enem

≤4

8≥

16

AM

INO

GLY

CO

SID

ESY.

pes

tisG

enta

mic

in≤

48

≥ 16

Stre

ptom

ycin

≤ 4

8≥

16F.

tula

rens

isG

enta

mic

in≤≤

4-

-Se

e co

mm

ent (

6).

Stre

ptom

ycin

≤≤8

--

See

com

men

t (6)

.TE

TRA

CYC

LIN

ESB.

ant

hrac

isTe

tracy

clin

e≤

1.0

--

(8)

Org

anis

ms

that

are

sus

cept

ible

to te

tracy

clin

e ar

e al

so c

onsi

dere

d su

scep

tible

todo

xycy

clin

e. H

owev

er, s

ome

orga

nism

s th

at a

re in

term

edia

te o

r res

ista

nt to

tetra

cycl

ine

may

be

susc

eptib

le to

dox

ycyc

line.

See

com

men

t (6)

. D

oxyc

yclin

e≤

1.0

--

B. m

alle

iB.

pse

udom

alle

i Y.

pes

tis

Tetra

cycl

ine

≤ 4

8≥

16S

ee c

omm

ent (

8).

Dox

ycyc

line

≤ 4

8≥

16

F. tu

lare

nsis

Tetr

acyc

line

≤≤ 4

--

See

com

men

ts (6

) and

(8).

Dox

ycyc

line

≤≤ 4

--

FLU

OR

OQ

UIN

OLO

NES

B. a

nthr

acis

Cip

roflo

xaci

n≤

0.5

--

See

com

men

t (6)

.Y.

pes

tisC

ipro

floxa

cin

≤ 1

2≥

4F.

tula

rens

isC

ipro

floxa

cin

≤≤ 0.

5-

-Se

e co

mm

ent (

6).

Levo

floxa

cin

≤≤ 0.

5-

-Se

e co

mm

ent (

6).

FOLA

TE P

ATH

WAY

INH

IBIT

OR

SB.

pse

udom

alle

iY.

pes

tisTr

imet

hopr

im-s

ulfa

met

hoxa

zole

≤ 2/

38-

≥4/

76

PHEN

ICO

LSY.

pes

tisC

hlor

amph

enic

ol≤

816

≥ 32

F. tu

lare

nsis

Chl

oram

phen

icol

≤≤ 8

--

See

com

men

t (6)

.

Tabl

e 2K

. (C

ontin

ued)



Tabl

e 2L

. MIC

Inte

rpre

tive

Stan

dard

s (µµ

g/m

L) fo

r N

eiss

eria

men

ingi

tidis

Test

ing

Con

ditio

ns

Med

ium

: B

roth

m

icro

dilu

tion:

C

atio

n-ad

just

ed

Mue

ller-

Hin

ton

brot

h(C

AM

HB

) sup

plem

ente

d w

ith 2

to 5

% ly

sed

hors

e bl

ood.

A

gar

dilu

tion:

M

uelle

r-H

into

n ag

ar

supp

lem

ente

d w

ith

5%de

fibrin

ated

she

ep b

lood

.In

ocul

um:

Dire

ct c

olon

y su

spen

sion

fro

m a

20

to 2

4 h

grow

th f

rom

Cho

cola

te a

gar

incu

bate

d at

35

°C; 5

% C

O2;

equ

ival

ent t

o a

0.5

McF

arla

nd s

tand

ard.

Col

onie

s gr

own

on s

heep

blo

od a

gar m

aybe

use

d fo

r in

ocul

um p

repa

ratio

n. H

owev

er, t

he 0

.5 M

cFar

land

susp

ensi

on

obta

ined

fr

om

shee

p bl

ood

agar

w

ill

cont

ain

appr

oxim

atel

y 50

% f

ewer

CFU

/mL.

Thi

s m

ust

be t

aken

int

oac

coun

t w

hen

prep

arin

g th

e fin

al

dilu

tion

prio

r to

pa

nel

inoc

ulat

ion,

as

guid

ed b

y co

lony

cou

nts.

Incu

batio

n:

35 °

C ±

2 de

gree

s; 5

% C

O2;

20

to 2

4 ho

urs

Tabl

e 2L

Nei

sser

ia m

enin

gitid

isM

7-M

IC

Min

imal

QC

Rec

omm

enda

tions

(See

Tab

les

3 an

d 3A

for

acce

ptab

leQ

C r

ange

s).

Stre

ptoc

occu

s pn

eum

onia

e AT

CC

®49

619

incu

bate

d ei

ther

in

ambi

ent

air

or 5

% C

O2,

exc

ept

that

azi

thro

myc

in Q

C t

ests

mus

t be

incu

bate

d in

am

bien

t air.

E.

col

iAT

CC

®25

922

(incu

bate

d ei

ther

in

ambi

ent

air

or 5

% C

O2)

shou

ld b

e us

ed f

or c

ipro

floxa

cin,

nal

idix

ic a

cid,

min

ocyc

line,

and

sulfi

soxa

zole

.

Gen

eral

Com

men

ts

(1)

Rec

omm

ende

d pr

ecau

tions

: B

iosa

fety

Lev

el 2

(B

SL2)

pra

ctic

es a

re r

ecom

men

ded

for

this

org

anis

m.

Whe

neve

r po

ssib

le,

proc

edur

es li

kely

to g

ener

ate

aero

sols

sho

uld

be p

erfo

rmed

with

in a

bio

logi

cal s

afet

y ca

bine

t.

(2)

Inte

rpre

tive

crite

ria a

re b

ased

upo

n po

pula

tion

dist

ribut

ions

of

MIC

s of

var

ious

age

nts,

pha

rmac

okin

etic

s of

the

age

nts,

prev

ious

ly p

ublis

hed

liter

atur

e, a

nd th

e cl

inic

al e

xper

ienc

e of

cer

tain

mem

bers

of t

he s

ubco

mm

ittee

. Sys

tem

atic

ally

col

lect

edcl

inic

al d

ata

wer

e no

t ava

ilabl

e to

rev

iew

with

man

y of

the

antim

icro

bial

age

nts

in th

is ta

ble.

(3)

For

som

e or

gani

sm/a

ntim

icro

bial

age

nt c

ombi

natio

ns,

the

abse

nce

of r

esis

tant

str

ains

pre

clud

es d

efin

ing

any

resu

ltsca

tego

ries

othe

r th

an “

susc

eptib

le.”

For

str

ains

yie

ldin

g re

sults

sug

gest

ive

of a

“no

nsus

cept

ible

” ca

tego

ry,

orga

nism

iden

tific

atio

n an

d an

timic

robi

al s

usce

ptib

ility

tes

t re

sults

sho

uld

be c

onfir

med

. Sub

sequ

ently

, the

isol

ates

sho

uld

be s

aved

and

subm

itted

to a

ref

eren

ce la

bora

tory

that

will

con

firm

res

ults

usi

ng a

CLS

I/NC

CLS

ref

eren

ce d

ilutio

n m

etho

d.

(4)

With

azi

thro

myc

in,

brea

kpoi

nts

wer

e de

velo

ped

initi

ally

usi

ng M

ICs

dete

rmin

ed b

y in

cuba

tion

in a

mbi

ent

air

for

the

phar

mac

odyn

amic

cal

cula

tions

.

(5)

Inst

ruct

ions

for

pre

para

tion

of l

ysed

hor

se b

lood

are

pro

vide

d in

CLS

I/NC

CLS

doc

umen

t M

7—M

etho

ds f

or D

ilutio

nA

ntim

icro

bial

Sus

cept

ibili

ty T

estin

g fo

r Bac

teria

that

Gro

w A

erob

ical

ly.

NO

TE:

Info

rmat

ion

in b

oldf

ace

type

is c

onsi

dere

d te

ntat

ive

for

one

year

.



Tabl

e 2L

Nei

sser

ia m

enin

gitid

isM

7-M

IC

Test

/Rep

ort

Gro

upA

ntim

icro

bial

Age

ntM

IC (µ

g/m

L)In

terp

retiv

e St

anda

rdC

omm

ents

SI

RPE

NIC

ILLI

NS

C CPe

nici

llin

Am

pici

llin

≤≤0.

06≤≤

0.12

0.12

-0.2

50.

25-1

≥≥ 0.

5≥≥

2C

EPH

EMS

(PA

REN

TER

AL)

(Inc

ludi

ng c

epha

losp

orin

s I,

II, II

I, an

d IV

. Ple

ase

refe

r to

Glo

ssar

y I.)

C CC

efot

axim

e or

ceftr

iaxo

ne≤≤

0.12

≤≤

0.12

– –

– –Se

e co

mm

ent (

3).

CA

RB

APE

NEM

SC

Mer

open

em≤≤

0.25

––

See

com

men

t (3)

.M

AC

RO

LID

ESC

Azi

thro

myc

in≤≤

2 –

–Se

e co

mm

ents

(3) a

nd (4

).(6

) May

be

appr

opria

te o

nly

for

prop

hyla

xis

of m

enin

goco

ccal

cas

e co

ntac

ts. T

hese

brea

kpoi

nts

do n

ot a

pply

to

ther

apy

of p

atie

nts

with

inv

asiv

e m

enin

goco

ccal

dise

ase.

TETR

AC

YCLI

NES

CM

inoc

yclin

e≤≤

2 –

–Se

e co

mm

ents

(3) a

nd (6

).

FLU

OR

OQ

UIN

OLO

NES

C CC

ipro

floxa

cin

Levo

floxa

cin

≤≤0.

03≤≤

0.03

0.06

0.06

≥≥0.

12

≥≥0.

12

See

com

men

t (6)

.(7

) Fo

r su

rvei

llanc

e pu

rpos

es,

a na

lidix

ic a

cid

MIC

≥≥8

µg/m

Lm

ay c

orre

late

with

dim

inis

hed

fluor

oqui

nolo

ne s

usce

ptib

ility

.FO

LATE

PAT

HW

AYIN

HIB

ITO

RS

C CSu

lfiso

xazo

leTr

imet

hopr

im-

sulfa

met

hoxa

zole

≤≤2

≤≤0.

12/2

.34 0.

25/4

.75

≥≥8

≥≥0.

5/9.

5 Se

e co

mm

ent (

6).

PHEN

ICO

LS CC

hlor

amph

enic

ol≤≤

2 4

≥≥8

AN

SAM

YCIN

SC

Rifa

mpi

n≤≤

0.5

1≥≥

2Se

e co

mm

ent (

6).

Tabl

e 2L

. (C

ontin

ued)

140

Tabl

e 3

Non

fast

idio

us Q

ualit

y C

ontro

lM

7-M

IC


January 2005 Vol. 25 No. 1Table 3. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of MinimalInhibitory Concentrations (MICs) (µµg/mL) of Nonfastidious Organisms (Using Cation-AdjustedMueller-Hinton Medium Without Blood or Other Nutritional Supplements)

Antimicrobial Agent


ATCC® 29213a

Enterococcusfaecalis

ATCC® 29212

Escherichiacoli

ATCC® 25922


ATCC® 27853

Escherichiacoli

ATCC® 35218b

AmikacinAmoxicillin-clavulanic acidAmpicillinAmpicillin-sulbactamAzithromycinAzlocillinAztreonamCarbenicillinCefaclorCefamandoleCefazolinCefdinirCefditorenCefepimeCefetametCefiximeCefmetazoleCefonicidCefoperazoneCefotaximeCefotetanCefoxitinCefpodoximeCefprozilCeftazidimeCeftibutenCeftizoximeCeftriaxoneCefuroximeCephalothinChloramphenicolCinoxacinCiprofloxacinClarithromycinClinafloxacinClindamycinc

ColistinDalbavancinDaptomycind

DirithromycinDoripenemDoxycyclineEnoxacinErtapenemErythromycinc

FleroxacinFosfomycine

GarenoxacinGatifloxacinGemifloxacinGentamicinf

GrepafloxacinImipenemKanamycinLevofloxacinLinezolidLomefloxacin

1-40.12/0.06-0.5/0.25

0.5-2-

0.5-22-8

-2-81-4

0.25-10.25-1

0.12-0.50.25-2

1-4-

8-320.5-21-41-41-4

4-161-41-8

0.25-14-16

-2-81-8

0.5-20.12-0.5

2-16-

0.12-0.50.12-0.5

0.008-0.060.06-0.25

-0.03-0.12

0.25-11-4

0.015-0.060.12-0.5

0.5-20.06-0.25

0.25-10.25-10.5-4

0.004-0.030.03-0.12

0.008-0.030.12-1

0.03-0.120.015-0.06

1-40.06-0.5

1-40.25-2

64-2560.25/0.12-1.0/0.5

0.5-2--

1-4-

16-64----------------------

4-16-

0.25-2-

0.03-0.254-16

-0.03-0.12

1-4-

1-42-8

2-164-161-42-8

32-1280.03-0.250.12-1.0

0.015-0.124-16

0.12-0.50.5-216-640.25-2

1-42-8

0.5-42/1-8/4

2-82/1-8/4

-8-32

0.06-0.254-161-4

0.25-11-4

0.12-0.50.12-1

0.015-0.120.25-10.25-10.25-10.25-1

0.12-0.50.03-0.120.06-0.25

2-80.25-1

1-40.06-0.50.12-0.5

0.03-0.120.03-0.12

2-84-162-82-8

0.004-0.015-

0.002-0.015-

0.25-1---

0.015-0.060.5-2

0.06-0.250.004-0.015

-0.03-0.12

0.5-20.004-0.030.008-0.03

0.004-0.0150.25-1

0.004-0.030.06-0.25

1-40.008-0.06

-0.03-0.12

1-4----

2-82-8

16-64-----

1-8--

> 32-

2-88-32

----

1-4-

16-648-64

----

0.25-1-

0.06-0.5-

0.25-2---

0.12-0.5-

2-82-8

-1-42-8

0.5-20.5-2

0.25-10.5-2

0.25-2.01-4

-0.5-4

-1-4

-4/2-16/8

-8/4-32/16

-----------------------------------------------------



NOTE 1: These MICs were obtained in several reference laboratories by broth microdilution. If four or fewerconcentrations are tested, quality control may be more difficult.

NOTE 2: Information in boldface type is considered tentative for one year.NOTE 3: For four-dilution ranges, results at the extremes of the acceptable range(s) should be suspect. Verify control

validity with data from other control strains.

Footnotesa. ATCC is a registered trademark of the American Type Culture Collection.b. Because this strain may lose its plasmid, careful organism maintenance is required; refer to M7, Section 12.4. c. When disk approximation tests are performed with erythromycin and clindamycin, S. aureus ATCC® BAA-977

(containing inducible ermA-mediated resistance) and S. aureus ATCC® BAA-976 (containing msrA-mediated macrolide-only efflux) are recommended for quality assessment purposes (e.g., training, competency assessment, or testevaluation). S. aureus ATCC® BAA-977 should demonstrate inducible clindamycin resistance (i.e., a positive D-zonetest), while S. aureus ATCC® BAA-976 should not demonstrate inducible clindamycin resistance. S. aureus ATCC®25923 should be used for routine quality control (e.g., weekly or daily) of erythromycin and clindamycin disks usingstandard Mueller-Hinton agar.

d. QC ranges reflect MICs obtained when Mueller-Hinton broth is supplemented with calcium to a final concentration of50 µg/mL.

e. The approved MIC susceptibility testing method is agar dilution. Agar media should be supplemented with 25 µg/mL ofglucose-6-phosphate. Broth dilution should not be performed.

f. For control organisms for gentamicin and streptomycin high-level aminoglycoside screen tests for enterococci, see Table2D.

g. This test should be performed by agar dilution only.h. Very medium-dependent, especially with enterococci.i. The quality control limits for E. coli ATCC® 35218 when using Haemophilus Test Medium (HTM) are 16/2 to 64/2 µg/mL.j. For broth microdilution testing of tigecycline, when MIC panels are prepared, the medium must be prepared

fresh on the day of use. The medium must be no greater than 12 hours old at the time the panels are made,however, the panels may then be frozen for later use.

k. For control organisms for vancomycin screen test for enterococci, see Table 2D.


Tabl

e 3

Non

fast

idio

us Q

ualit

y C

ontro

lM

7-M

IC

Antimicrobial Agent


ATCC® 29213a

Enterococcusfaecalis

ATCC® 29212

Escherichiacoli

ATCC® 25922


ATCC® 27853

Escherichiacoli

ATCC® 35218b

LoracarbefMecillinamMeropenemMethicillinMezlocillinMinocyclineMoxalactamMoxifloxacinNafcillinNalidixic acidNetilmicinNitrofurantoinNorfloxacinOfloxacinOritavancinOxacillinPenicillinPiperacillinPiperacillin-tazobactamPolymyxin BQuinupristin-dalfopristinRifampinSparfloxacinSulfisoxazoleh

TeicoplaninTelavancinTelithromycinTetracyclineTicarcillinTicarcillin-clavulanic acidTigecycline j

TobramycinTrimethoprimh

Trimethoprim-sulfamethoxazoleTrospectomycinTrovafloxacinVancomycink

0.5-2-

0.03-0.120.5-21-4

0.06-0.54-16

0.015-0.120.12-0.5

-≤ 0.258-320.5-2

0.12-10.5-2

0.12-0.50.25-2

1-40.25/4-2/4

-0.25-1

0.004-0.0150.03-0.1232-1280.25-10.12-1

0.06-0.250.12-1

2-80.5/2-2/20.03-0.25

0.12-11-4

≤ 0.5/9.52-16

0.008-0.030.5-2

--

2-8>161-41-4

-0.06-0.5

2-8-

4-164-162-81-4

0.12-18-321-41-4

1/4-4/4-

2-80.5-4

0.12-0.532-128

0.06-0.250.12-0.5

0.015-0.128-32

16-6416/2-64/20.03-0.12

8-32≤ 1

≤ 0.5/9.52-8

0.06-0.251-4

0.5-20.03-0.25f

0.008-0.06-

2-80.25-1

0.12-0.50.008-0.06

-1-4

≤ 0.5-14-16

0.03-0.120.015-0.12

---

1-41/4-4/40.25-2

-4-16

0.004-0.0158-32

---

0.5-24-16

4/2-16/20.03-0.25

0.25-10.5-2

≤ 0.5/9.58-32

0.004-0.015-

>8-

0.25-1-

8-32-

8-321-8

--

0.5-8-

1-41-8

---

1-81/4-8/40.25-2

-16-640.5-2

----

8-328-32

8/2-32/2-

0.25-1>64

8/152-32/608-

0.25-2-

------------------

0.5/4-2/4----------

8/2-32/2i

-------


142

Tabl

e 3A

Fast

idio

us Q

ualit

y C

ontro

lM

7-M

IC


Table 3A. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of MinimalInhibitory Concentrations (MICs) (µg/mL) of Fastidious Organisms

Antimicrobial Agent


ATCC® 49247a


ATCC®

49766

Neisseria gonorrhoeaeATCC® 49226


ATCC® 49619

Helicobacterpylori

ATCC® 43504

Campylobacterjejuni

ATCC® 33560b

36 °C/48 hours

Campylobacterjejuni

ATCC® 33560b

42 °C/24 hours

Amoxicillinc

Amoxicillin-clavulanic acidc

Ampicillin Ampicillin-

sulbactamAzithromycin Aztreonam CefaclorCefamandoleCefdinirCefditorenCefepimeCefetametCefiximeCefmetazoleCefonicidCefotaximeCefotetanCefoxitinCefpiromeCefpodoxime Cefprozil Ceftazidime Ceftibuten Ceftizoxime Ceftriaxone Cefuroxime Cephalothin ChloramphenicolCiprofloxacin Clarithromycin ClinafloxacinClindamycinDalbavancinDaptomycind

DirithromycinDoripenemDoxycyclineEnoxacin ErtapenemErythromycinFleroxacinGarenoxacinGatifloxacinGemifloxacinGentamicinGrepafloxacinImipenemLevofloxacinLinezolidLomefloxacinLoracarbefMeropenemMetronidazoleMoxifloxacinNitrofurantoin

- 2/1-16/8

2-82/1-8/4

1-40.12-0.5

---

0.06-0.250.5-20.5-20.12-12-16

-0.12-0.5

--

0.25-10.25-1

- 0.12-1 0.25-1

0.06-0.5 0.06-0.25

- -

0.25-1 0.004-0.03

4-160.001-0.008

---

8-32-----

0.03-0.120.002-0.0080.004-0.030.002-0.008

-0.002-0.015

-0.008-0.03

-0.03-0.12

---

0.008-0.03-

--

--

--

1-40.25-1

0.12-0.5-----

0.06-0.25-----

1-4 ----

0.25-1 ---------

0.06-0.25--

0.015-0.06 -------

0.25-1---

0.5-20.03-0.12

---

--

--

--- -

0.008-0.03-

0.015-0.060.015-0.250.004-0.03

0.5-2-

0.015-0.060.5-20.5-2

-0.03-0.12

- 0.03-0.12

- 0.008-0.03 0.004-0.015

0.25-1 - -

0.001-0.008--------

0.015-0.06- -

0.008-0.03-

0.002-0.015--

0.004-0.03---

0.008-0.03-----

0.03-0.120.03/0.015 -

0.12/0.060.06-0.25

-

0.06-0.25-

1-4-

0.03-0.250.015-0.120.03-0.25

0.5-2---

0.03-0.12---

0.03-0.12 0.25-1

- -

0.12-0.50.03-0.12

0.25-1 0.5-2 2-8

- 0.03-0.120.03-0.120.03-0.120.008-0.030.06-0.50.06-0.250.03-0.120.015-0.12

-0.03-0.25 0.03-0.12

-0.015-0.060.12-0.5

0.008-0.03-

0.06-0.50.03-0.12

0.5-20.5-2

-2-8

0.06-0.25-

0.06-0.254-16

0.015-0.12-

- -

- - - - - - - - - - - - - - - - - - - - - - - - -

0.015-0.12--------- -------------

64-256--

- -

- -

- - - - ----------- -- - - - - - - -

0.12-1-------

0.5-2--

1-8----

0.5-2------

0.004-0.015---

- -

- -

- - - - - - - - - - - - - -- - - - - - - - - -

0.06-0.5 -------

0.25-2--

1-4----

0.5-4------

0.008-0.03---


Tabl

e 3A

Fast

idio

us Q

ualit

y C

ontro

lM

7-M

IC


Organism Haemophilusinfluenzae Neisseria gonorrhoeae Streptococcus

pneumoniaeHelicobacter

pyloriCampylobacter

spp.

Medium

Broth dilution:HaemophilusTest Medium(HTM) broth

Agar dilution: GC agar baseand 1% defined growthsupplement. The use of acysteine-free supplement isrequired for agar dilutiontests with carbapenems andclavulanate. Cysteine-containing defined growthsupplements do notsignificantly alter dilution testresults with other drugs.

Broth dilution: Cation-adjusted Mueller-Hinton broth with lysedhorse blood (2-5% v/v).

Agar Dilution:Mueller-Hintonagar with aged(≥ 2-week-old)sheep blood (5%v/v).

Agar dilution:Mueller-Hintonagar with 5%defibrinatedsheep blood

Inoculum Direct colonysuspension,equivalent to a0.5 McFarlandstandard

Direct colony suspension,equivalent to a 0.5McFarland standard

Direct colonysuspension, equivalentto a 0.5 McFarlandstandard

See footnote f,below.

Direct colonysuspension,equivalent to a0.5 McFarlandstandard

IncubationCharacteristics

35 °C; ambientair; 20-24 hours

35 °C; 5% CO2; 20-24 hours 35 °C; ambient air; 20-24 hours

35 °C; three days;microaerobicatmosphereproduced by gas-generating systemsuitable forcampylobacters

36 °C /48 hoursor 42 °C/ 24hours; 10% CO2,5% O2 and 85%N2 or amicroaerophilicenvironment

Testing Conditions for Clinical Isolates and Performance of Quality Control

NOTE 1: Information in boldface type is considered tentative for one year.NOTE 2: For four-dilution ranges, results at the extremes of the acceptable range(s) should be suspect. Verify control validity

with data from other control strains.Footnotes

a. ATCC is a registered trademark of the American Type Culture Collection.b. Since some isolates of C. jejuni ssp. doylei, C. fetus, and C. lari may not grow at 42 °C, susceptibility testing of these isolates

should be performed at 36 °C.c. Quality control limits for E. coli ATCC® 35218 when tested on HTM are 4/2 to 16/8 µg/mL for amoxicillin-clavulanic acid and

≥ 256 µg/mL for amoxicillin; testing amoxicillin may help to determine if the isolate has maintained its ability to produce β-lactamase.

d. QC ranges reflect MICs obtained when Mueller-Hinton broth is supplemented with calcium to a final concentration of 50 µg/mL.e. For broth microdilution testing of tigecycline, when MIC panels are prepared, the medium must be prepared fresh on

the day of use. The medium must be no greater than 12 hours old at the time the panels are made, however, the panelsmay then be frozen for later use.

f. The inoculum for testing of H. pylori should be as follows: a saline suspension equivalent to a 2.0 McFarland standard(containing 1x107 to 1x108 CFU/mL), to be prepared from a 72-hour-old subculture from a blood agar plate. The inoculum (1to 3 µL per spot) is replicated directly on the antimicrobial agent-containing agar dilution plates.


Antimicrobial Agent


ATCC® 49247a


ATCC® 49766

Neisseria gonorrhoeaeATCC® 49226

StreptococcuspneumoniaeATCC® 49619

HelicobacterpyloriATCC®

43504

Campylobacterjejuni

ATCC® 33560b

36 °C/48 hours

Campylobacterjejuni

ATCC® 33560b

42 °C/24 hours

NorfloxacinOfloxacinOritavancinPenicillinPiperacillin-tazobactamQuinupristin-

dalfopristinRifampinSparfloxacinSpectinomycinTelavancinTelithromycinTetracyclineTigecycline

e


TrospectomycinTrovafloxacinVancomycin

-0.015-0.06

--

0.06/4-0.5/42-8

0.25-10.004-0.015

--

1-44-32

0.06-0.50.03/0.59-0.25/4.75

0.5-20.004-0.015

-

------

--------

---

-0.004-0.015

-0.25-1

--

- 0.004-0.015

8-32--

0.25-1--

1-40.004-0.015

-

2-8 1-4

0.008-0.060.25-1

-0.25-1

0.015-0.060.12-0.5

- 0.002-0.0150.004-0.03

0.12-0.50.015-0.120.12/2.4-

1/191-4

0.06-0.250.12-0.5

------

----

0.06-0.50.12-1.0

--

---

------

--------

---

------

--------

---



Table 3B. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of MinimalInhibitory Concentrations (MICs) (µµg/mL) Generated in Cation-Adjusted Mueller-Hinton Broth + 2%Defined Growth Supplement

AntimicrobialAgent

Staphylococcus aureus

ATCC® 29213 24 hours

Staphylococcus aureus

ATCC® 29213 48 hours

Escherichia coli

ATCC® 2592224 hours

Escherichia coli






CiprofloxacinChloramphenicolDoxycyclineGentamicinLevofloxacinNalidixic AcidStreptomycinTetracyclineTrimethoprim-

sulfamethoxazole

0.25-14-16

0.12-10.25-1

0.12-0.5—

8-320.25-2

≤≤0.25/4.75

0.25-14-32

0.25-20.25-1

0.12-0.5—

8-640.5-4

≤≤0.25/4.75

0.004-0.0162-81-4

0.25-20.008-0.03

1-88-321-4

≤≤0.5/9.5

0.004-0.034-161-8

0.25-20.008-0.06

2-88-322-8

≤≤0.5/9.5

0.12-1—

4-320.5-20.5-2

—32-128

8-32—

0.25-1 —

4-32 0.5-4 0.5-4

—32-256

8-64 —

Note 1: Francisella tularensis MIC results read after 24 hours of incubation should use 24-hour QC ranges;results read after 48 hours should use only the 48-hour QC ranges.

Tabl

e 3B

QC

Mon

itorin

g fo

r CA

MH

B+

2% D

efin

ed G

row

th S

uppl

emen

tM

7-M

IC

For Use With M7-A6–MIC Testing M100-S15Table 3C. Reference Guide to Quality Control Testing Frequency

This table summarizes the suggested frequency of testing CLSI/NCCLS-recommended ATCC qualitycontrol strains to be performed by the user of antimicrobial susceptibility tests (AST). It applies only toantimicrobial agents for which 20 or 30 consecutive test days of quality control testing producedsatisfactory results.

Number of days of consecutiveQC testing required

a

Test Modification 1 5 20 or 30 CommentsMIC Test(s)

Use new shipment or lot number X

Expand dilution range X Example:Convert from breakpoint to expandedrange MIC panels.

Reduce dilution range X Example:Convert from expanded dilution rangeto breakpoint panels.

Use new method (same company) X Examples:Convert from visual to instrument reading of panel.

Convert from overnight to rapid MICtest.

In addition, perform in-house validationstudies.

Use new manufacturer of MIC test X In addition, perform in-house validationstudies.

Inoculum PreparationConvert inoculum preparation/standardization to use of a device thathas its own QC protocol

X Example:Convert from visual adjustment of turbidity to use of a photometric devicefor which a quality control procedure isprovided.

Convert inoculum preparation/standardization to a method that isdependent on user technique

X Example:Convert from visual adjustment of turbidity to another method that is notbased on a photometric device.

Instrument/SoftwareSoftware update that affects AST results X Monitor all drugs, not just those

implicated in software modification.Repair of instrument that affects ASTresults

X Depending on extent of repair (e.g.,critical component such as the optics),additional testing may be appropriate(e.g., five days).

Tabl

e 3C

QC

Tes

ting

Freq

uenc

yM

7-M

ICNOTE 1: Addition of any NEW antimicrobial agent requires 20 or 30 consecutive days of satisfactory testing (see M7-A6, Section 12.7)

prior to use of this guide.

NOTE 2: QC can be performed prior to or concurrent with testing patient isolates. Patient results can be reported for that day if quality control results are within the acceptable limits.

NOTE 3: Manufacturers of commercial or in-house prepared tests should follow their own internal procedures and applicable regulations.

NOTE 4: Acceptable MIC QC limits for FDA-cleared antimicrobial susceptibility tests may differ slightly from acceptableCLSI/NCCLS QC limits. Users of each device should utilize manufacturer’s procedures and QC limits as indicated in theinstructions for use.

NOTE 5: For troubleshooting out-of-range results, refer to M7-A6, Section 12.9.

NOTE 6: Broth, saline, and/or water used to prepare an inoculum does not require routine quality control.

Footnote

a. Does not eliminate the need for routine weekly or daily QC testing.©Clinical and Laboratory Standards Institute. All rights reserved. 145

146

Tabl

e 4

Solv

ents

and

Dilu

ents

M7-

MIC


January 2005 Vol. 25 No. 1Table 4. Solvents and Diluents for Preparation of Stock Solutions of Antimicrobial Agents

Antimicrobial Agent Solvent DiluentAmikacin WaterAmoxicillin Phosphate buffer, pH 6.0, 0.1 mol/L Phosphate buffer, pH 6.0, 0.1 mol/LAmpicillin Phosphate buffer, pH 8.0, 0.1 mol/L Phosphate buffer, pH 6.0, 0.1 mol/LAzithromycin 95% ethanol or glacial acetic acidf Broth mediaAzlocillin WaterAztreonam Saturated solution sodium bicarbonate WaterCarbenicillin WaterCefaclor WaterCefadroxil Phosphate buffer, pH 6.0, 0.1 mol/L WaterCefamandole WaterCefazolin Phosphate buffer, pH 6.0, 0.1 mol/L Phosphate buffer, pH 6.0, 0.1 mol/LCefdinir Phosphate buffer, pH 6.0, 0.1 mol/L WaterCefditoren Phosphate buffer, pH 6.0, 0.1 mol/L WaterCefepime Phosphate buffer, pH 6.0, 0.1 mol/L Phosphate buffer, pH 6.0, 0.1 mol/LCefetamet Phosphate buffer, pH 6.0, 0.1 mol/L WaterCefixime Phosphate buffer, pH 7.0, 0.1 mol/L Phosphate buffer, pH 7.0, 0.1 mol/LCefmetazole WaterCefonicid WaterCefoperazone WaterCefotetan Dimethyl sulfoxidee WaterCefotaxime WaterCefoxitin WaterCefpodoxime 0.10% (11.9 mmol/L) aqueous sodium bicarbonate WaterCefprozil WaterCeftazidime Sodium carbonated WaterCeftibuten 1/10 vol DMSO WaterCeftizoxime WaterCeftriaxone WaterCefuroxime Phosphate buffer, pH 6.0, 0.1 mol/L Phosphate buffer, pH 6.0, 0.1 mol/LCephalexin Phosphate buffer, pH 6.0, 0.1 mol/L WaterCephalothin Phosphate buffer, pH 6.0, 0.1 mol/L WaterCephapirin Phosphate buffer, pH 6.0, 0.1 mol/L WaterCephradine Phosphate buffer, pH 6.0, 0.1 mol/L WaterChloramphenicol 95% ethanol WaterCinoxacin 1/2 volume of water, then add 1 mol/L NaOH, Water

dropwise to dissolveCiprofloxacin WaterClarithromycin Methanole or glacial acetic acidf Phosphate buffer, pH 6.5, 0.1 mol/LClavulanic acid Phosphate buffer, pH 6.0, 0.1 mol/L Phosphate buffer, pH 6.0, 0.1 mol/LClinafloxacin WaterClindamycin WaterColistin

aWater Water

Dalbavancin DMSO WaterDaptomycin Water Water

147

Tabl

e 4

Solv

ents

and

Dilu

ents

M7-

MIC



Antimicrobial Agent Solvent DiluentDirithromycin Glacial acetic acidf WaterDoripenem 0.85% physiological saline 0.85% physiological salineDoxycycline WaterEnoxacin 1/2 volume of water, then 0.1 mol/L NaOH dropwise Water

to dissolveErtapenem Phosphate buffer, pH 7.2, 0.01 mol/L Phosphate buffer, pH 7.2, 0.01 mol/LErythromycin 95% ethanol or glacial acetic acidf WaterFleroxacin 1/2 volume of water, then 0.1 mol/L NaOH dropwise Water

to dissolveGarenoxacin Water (with stirring)Gatifloxacin Water (with stirring)Gemifloxacin WaterGentamicin WaterImipenem Phosphate buffer, pH 7.2, 0.01 mol/L Phosphate buffer, pH 7.2, 0.01 mol/LKanamycin WaterLevofloxacin 1/2 volume of water, then 0.1 mol/L NaOH dropwise Water

to dissolveLinezolid WaterLomefloxacinLoracarbef WaterMecillinam WaterMeropenem WaterMethicillin WaterMetronidazole Dimethyl sulfoxidee WaterMezlocillin WaterMinocycline WaterMoxalactam 0.04 mol/L HCl (let sit for 1.5 to 2 h) Phosphate buffer, pH 6.0, 0.1 mol/L

(diammonium salt)b

Moxifloxacin WaterNafcillin WaterNalidixic acid 1/2 volume of water, then add 1 mol/L NaOH,

dropwise to dissolveNetilmicin WaterNitrofurantoinc Phosphate buffer, pH 8.0, 0.1 mol/L Phosphate buffer, pH 8.0, 0.1 mol/LNorfloxacin 1/2 volume of water, then 0.1 mol/L NaOH dropwise Water

to dissolveOfloxacin 1/2 volume of water, then 0.1 mol/L NaOH dropwise Water

to dissolveOxacillin WaterPenicillin WaterPiperacillin WaterPolymyxin B Water WaterQuinupristin-dalfopristin WaterRifampin Methanole [maximum concentration = 640 µg/mL] Water (with stirring)Sparfloxacin WaterSpectinomycin WaterStreptomycin Water

Sulbactam Water

148

Tabl

e 4

Solv

ents

and

Dilu

ents

M7-

MIC



Footnotes

a. The formulation of colistin used in antimicrobial susceptibility tests is colistin sulfate and notcolistin methane sulfonate (sulfomethate).

b. The diammonium salt of moxalactam is very stable, but it is almost pure R isomer. Moxalactam for clinicaluse is a 1:1 mixture of R and S isomers. Therefore, the salt is dissolved in 0.04 mol/L HCl and allowed toreact for 1.5 to 2 hours to convert it to equal parts of both isomers.

c. Alternatively, nitrofurantoin is dissolved in dimethyl sulfoxide.

d. Anhydrous sodium carbonate is used at a weight of exactly 10% of the ceftazidime to be used. The sodiumcarbonate is dissolved in solution in most of the required water. The antibiotic is dissolved in this sodiumcarbonate solution, and water is added to the desired volume. The solution is to be used as soon aspossible, but it can be stored up to six hours at no more than 25 °C.

e. These compounds are potentially toxic. Consult the material safety data sheets (MSDS) available from theproduct manufacturer before using any of these materials.

f. For glacial acetic acid, use 1/2 volume of water, then add glacial acetic acid dropwise until dissolved, notto exceed 2.5 µL/mL.

Antimicrobial Agent Solvent DiluentSulfonamides 1/2 volume hot water and minimal amount of Water

2.5 mol/L NaOH to dissolveTazobactam WaterTelavancin DMSO WaterTelithromycin Glacial acetic acidf Water Tetracycline WaterTicarcillin Phosphate buffer, pH 6.0, 0.1 mol/L Phosphate buffer, pH 6.0, 0.1 mol/LTigecycline Water WaterTobramycin WaterTrimethoprim 0.05 mol/L lactice or hydrochlorice acid, Water (may require heat)

10% of final volumeTrimethoprim (if lactate) WaterTrospectomycin Water

Vancomycin WaterNOTE: Information in boldface type is considered tentative for one year.


149

Tabl

e 5

Dilu

tion

Sche

me

for

Aga

r Dilu

tion

Tests

M7-

MIC



Table 5. Scheme for Preparing Dilutions of Antimicrobial Agents to Be Used in Agar DilutionSusceptibility Tests

Antimicrobial Solution

Step Conc. Source Vol. Diluent Intermediate Final Conc. Log2 Concentration at 1:10 Dilution in(µµg/mL) Agar (µµg/L)

5120 Stock - - 5120 512 9µg/mL(mg/L)

1 5120 Stock 2 mL 2mL 2560 256 82 5120 Stock 1 3 1280 128 73 5120 Stock 1 7 640 64 64 640 Step 3 2 2 320 32 55 640 Step 3 1 3 160 16 46 640 Step 3 1 7 80 8 37 80 Step 6 2 2 40 4 28 80 Step 6 1 3 20 2 19 80 Step 6 1 7 10 1 010 10 Step 9 2 2 5 0.5 -111 10 Step 9 1 3 2.5 0.25 -212 10 Step 9 1 7 1.25 0.125 -3

NOTE: This table is modified from Ericsson HM, Sherris JC. Antibiotic sensitivity testing. Report of an internationalcollaborative study. Acta Pathol Microbiol Scand. 1971;217 (suppl B):1-98.

150

Tabl

e 6

Dilu

tion

Sche

me

for

Bro

th D

ilutio

n Te

stsM

7-M

IC


January 2005 Vol. 25 No. 1Table 6. Scheme for Preparing Dilutions of Antimicrobial Agents to Be Used in Broth DilutionSusceptibility Tests

Antimicrobial Solution

NOTE: This table is modified from Ericsson HM, Sherris JC. Antibiotic sensitivity testing. Report of an internationalcollaborative study. Acta Pathol Microbiol Scand. 1971;217 (suppl B):1-90.

Footnotes

a. The volumes selected can be any multiple of these figures, depending on the number of tests to be performed.

b. CAMHB, cation-adjusted Mueller-Hinton broth. Adjustment with cations, if necessary, occurs before this step.

1 5120 µg/mL Stock 1 mL 9 mL 512 µg/mL 9

2

3

4

512

512

512

Step 1

Step 1

Step 1

1

1

1

1

3

7

256

128

64

8

7

65

6

7

64

64

64

Step 4

Step 4

Step 4

1

1

1

1

3

7

32

16

8

5

4

38

9

10

8

8

8

Step 7

Step 7

Step 7

1

1

1

1

3

7

4

2

1

2

1

0

11

12

13

1

1

1

Step 10

Step 10

Step 10

1

1

1

1

3

7

0.5

0.25

0.125

-1

-2

-3

CAMHBb FinalStep Concentration Source Volumea + Volumea = Concentration Log2

151

Tabl

e 7

Mod

ifica

tions

for L

ister

iasp

p.M

7-M

IC



CAMHB: cation-adjusted Mueller-Hinton brothLHB: lysed horse blood

Footnotes

a. WARNING: For Listeria spp., cephems may appear active in vitro but are not effective clinically and should not bereported as susceptible.

b. For some organism/antimicrobial combinations, the absence of resistant strains precludes defining any resultscategories other than “susceptible.” For strains yielding results suggestive of a “nonsusceptible” category, organismidentification and antimicrobial susceptibility test results should be confirmed. Subsequently, the isolates should besaved and submitted to a reference laboratory that will confirm results using a CLSI/NCCLS reference dilutionmethod.

NOTE 1: To prepare lysed horse blood (LHB), freeze-thaw until the blood is thoroughly lysed. Aseptically mix equalvolumes of LHB and sterile distilled water (now 50%). To be used in the broth test, the combination of brothand LHB must be clear, and this can be accomplished by centrifuging the 50% blood at 12 000 x g for 20minutes. Decant the supernatant; recentrifuge if necessary. Add appropriate amounts of the 50% LHB to thebroth medium to yield a final concentration of 2 to 5% LHB.


Table 7. Suggested Modifications of Standard Methods for Susceptibility Testing of Listeria spp.

Organism Method Medium Incubation Comments

Listeria spp.a Brothmicrodilution

CAMHB +LHB (2-5% v/v)

35 ºC; 16-20hours

ampicillinb

≤ 2 µg/mL = susceptible

penicillinb

≤ 2 µg/mL = susceptible

Tabl

e 8

Sugg

este

d Te

st R

esul

t Ver

ifica

tion

and

Org

anism

Iden

tific

atio

nM

7-M

ICJanuary 2005 Vol. 25 No. 1


a Category I When results listed in this category are observed on individual patient isolates, they should be verified by one or moreof the following:




interpretive criteria are provided in Tables 2A to 2J (listed with an “NS” above) and for staphylococci withvancomycin-intermediate or vancomycin-resistant results: 1) confirm the organism identification; 2) confirmthe antimicrobial susceptibility test results; 3) save the isolate; and 4) submit the isolate to a referencelaboratory that will test it by a CLSI/NCCLS reference dilution method.

b Category II When results listed in this category are observed on individual patient isolates, the verification steps as outlined forCategory I should be considered if the resistance is uncommon in a given institution.

c For these antimicrobial agent/organism combinations, resistance has not been documented to date.d When submitting reports to a public health laboratory, include antimicrobial susceptibility results forSalmonella spp. that are intermediate or resistant to 3rd-generation cephalosporins and/or intermediate orresistant to fluoroquinolone or resistant to nalidixic acid.

Table 8. Suggestions for Verification of Antimicrobial Susceptibility Test Results and Confirmationof Organism Identification

This table reflects the drugs listed for testing against the respective organisms in Tables 2A to 2J in M100and gives some examples to consider for verification protocols at a given institution. The list includesphenotypes that: 1) have never been documented; 2) are uncommon; and/or 3) represent results thatcould easily occur from technical errors and which may have significant clinical consequences.

Organism or Group Category Ia



Category IIb

Phenotypes that may be uncommon at a given institution and/or

result from technical errorsGram-negative organismsEnterobacteriaceae(any)

carbapenem - I or R amikacin - Rfluoroquinolone - R

Citrobacter freundiiEnterobacter spp.Serratia marcescens

ampicillin, cefazolin, or cephalothin- S

Escherichia coli ESBL confirmed positiveKlebsiella spp. ampicillin - S ESBL confirmed positiveProteus vulgarisProvidencia spp.

ampicillin - S

Salmonella spp. 3rd-generation cephalosporin - I or Rd

fluoroquinolone I or R or nalidixic acid - Rd

Pseudomonas aeruginosa

concurrent gentamicin and tobramycin andamikacin - R

Stenotrophomonas maltophilia

carbapenem - S trimethoprim-sulfamethoxazole - R

Haemophilus influenzae

aztreonam - NScarbapenem - NS3rd-generation cephalosporinc - NSfluoroquinolone - NS

ampicillin - R and β-lactamase- negativeamoxicillin-clavulanic acid-R


3rd-generation cephalosporin - R fluoroquinolone - R

Any organism Resistant to all agents routinelytested

153

Tabl

e 8

Sugg

este

d Te

st R

esul

t Ver

ifica

tion

and

Org

anism

Iden

tific

atio

nM

7-M

IC



aCategory I When results listed in this category are observed on individual patient isolates, they should be verified byone or more of the following:

1. Ensuring the unusual results are not due to transcription errors, contamination, or use of adefective panel, plate, or card.

2. Checking previous reports on the patient to determine if the isolate was encountered and verifiedearlier.

3. Confirming the identification of the isolate.4. Repeating the susceptibility test to confirm results. Sometimes it is helpful to use an alternative

test method for the repeat test. 5. For isolates that show results other than susceptible for those antimicrobial agents for which only

susceptible interpretive criteria are provided in Tables 2A to 2J (listed with an “NS” above) and forstaphylococci with vancomycin-intermediate or vancomycin-resistant results: 1) confirm theorganism identification; 2) confirm the antimicrobial susceptibility test results; 3) save the isolate;and 4) submit the isolate to a reference laboratory that will test it by a CLSI/NCCLS referencedilution method.

bCategory II When results listed in this category are observed on individual patient isolates, the verification steps asoutlined for Category I should be considered if the resistance is uncommon in a given institution.

c For these antimicrobial agent/organism combinations, resistance has not been documented to date.

Organism or Group Category Ia



Category IIb

Phenotypes that may be uncommon at a given institution

and/or result from technical errorsGram-positive organismsEnterococcus spp. daptomycin - NS vancomycin - REnterococcus faecalis ampicillin or penicillin - R

daptomycin - NSlinezolid - Rquinupristin-dalfopristin - S

high-level aminoglycoside - R(particularly if isolate from sterile body site)

Enterococcus faecium daptomycin - NSlinezolid - R

high-level aminoglycoside - R (particularly if isolate from sterilebody site)

quinupristin-dalfopristin - RStaphylococcus aureus daptomycin - NS

linezolid - NSquinupristin-dalfopristin - I or Rvancomycin - I or R

oxacillin - R

Staphylococcus, coagulase-negative

daptomycin - NSlinezolid - NSvancomycin - I or R


fluoroquinolone - Rlinezolidc - NSvancomycinc - NS

penicillin - R3rd-generation cephalosporin - R

Streptococcus, betagroup

ampicillin or penicillinc - NS3rd-generation cephalosporin - NSdaptomycin - NSlinezolid - NSvancomycinc - NS

Streptococcus, viridansgroup

daptomycin - NSlinezolid - NSvancomycin - NS

penicillin - I or R

Any organism Resistant to all agents routinely tested

January 2005 Vol. 25 No. 1G

loss

ary

I


Glossary I (Part 1). ββ-lactams: Class and Subclass Designation and Generic Name

a Penicillinase-labile; hydrolyzed by staphylococcal penicillinase.b Not hydrolyzed by staphylococcal penicillinase.c Cephalosporin I, II, III, and IV are sometimes referred to as 1st-, 2nd-, 3rd, and 4th-generation cephalosporins, respectively.

Cephalosporin III and IV are also referred to as “extended-spectrum cephalosporins.” This does not imply activity against ESBL-producing gram-negativebacteria.

d Although often referred to as a 2nd-generation cephalosporin, cephamycins are not included with the other cephalosporins with regard to reporting of ESBL-producing strains.

e For all confirmed ESBL-producing strains, the test interpretation should be reported as resistant for this antimicrobial class or subclass.

Antimicrobial Class Antimicrobial Subclass Agents Included; Generic Namespenicillins penicillina penicillin

aminopenicillina amoxicillin

ampicillinureidopencillina azlocillin

mezlocillinpiperacillin

carboxypenicillina carbenicillinticarcillin

penicillinase-stablepenicillins

b

cloxacillindicloxacillinmethicillinnafcillinoxacillin

amidinopenicillin mecillinamβ-lactam/β-lactamaseinhibitor combinations

amoxicillin-clavulanic acidampicillin-sulbactampiperacillin-tazobactamticarcillin-clavulanic acid

cephems (parenteral) cephalosporin Ic,e cefazolin

cephalothincephapirincephradine

cephalosporin IIc,e cefamandole

cefonicidcefuroxime (sodium)

cephalosporin IIIc,e cefoperazone

cefotaximeceftazidimeceftizoximeceftriaxone

cephalosporin IVc,e cefepime cephamycind cefmetazole

cefotetancefoxitin

oxacephem moxalactamcephems (oral) cephalosporine cefaclor

cefadroxilcefdinircefditorencefetametcefiximecefpodoximecefprozilceftibutencefuroxime (axetil)cephalexincephradine

carbacephem loracarbefmonobactams aztreonamcarbapenems doripenem

ertapenemimipenemmeropenem

For Use With M7-A6–MIC Testing M100-S15Glossary I (Part 2). Non-ββ-lactams: Class and Subclass Designation and Generic Name

Antimicrobial Class Antimicrobial Subclass Agents Included; Generic Namesaminocyclitols spectinomycin

trospectinomycinaminoglycosides amikacin

gentamicinkanamycinnetilmicinstreptomycintobramycin

ansamycins rifampinquinolones quinolone cinoxacin

garenoxacinnalidixic acid

fluoroquinolone ciprofloxacinclinafloxacinenoxacinfleroxacingatifloxacingemifloxacingrepafloxacinlevofloxacinlomefloxacinmoxifloxacinnorfloxacinofloxacinsparfloxacintrovafloxacin

folate pathway inhibitors sulfonamidestrimethoprimtrimethoprim-sulfamethoxazole

fosfomycins fosfomycinketolides telithromycinlincosamides clindamycinlipopeptides daptomycin

polymyxins colistin polymyxin B

macrolides azithromycinclarithromycindirithromycinerythromycin

nitrofurans nitrofurantoinnitroimidazoles metronidazoleoxazolidinones linezolidglycopeptides glycopeptide oritavancin

vancomycinlipoglycopeptide dalbavancin

teicoplanintelavancin

phenicols chloramphenicolstreptogramins quinupristin-dalfopristintetracyclines doxycycline

minocyclinetetracycline

glycylcycline tigecycline

Glo

ssar

y I



loss

ary

II


Glossary II. Abbreviations/Routes of Administration/Drug Class for Antimicrobial Agents Listedin M100-S15

Antimicrobial Agent Agent Abbreviationa Routes of Administrationb Drug ClassPO IM IV

Amikacin AN, AK, Ak, AMI, AMK

X X aminoglycoside

Amoxicillin AMX, Amx, AMOX, AC

X penicillin

Amoxicillin-clavulanic acid AMC, Amc, A/C, AUG, Aug, XL, AML

X β-lactam/β-lactamase inhibitor

Ampicillin AM, Am, AMP X X X penicillinAmpicillin-sulbactam SAM, A/S,

AMS, ABX β-lactam/β-lactamase

inhibitorAzithromycin AZM, Azi, AZI, AZ X X macrolideAzlocillin AZ, Az, AZL X X penicillinAztreonam ATM, AZT, Azt, AT, AZM X monobactam

Carbenicillin (indanyl salt)

Carbenicillin

CB, Cb, BAR X

X X

penicillin

Cefaclor CEC, CCL, Cfr, FAC, CF X cephemCefadroxil CFR, FAD X cephemCefamandole MA, CM, Cfm, FAM X X cephemCefazolin CZ, CFZ, Cfz, FAZ, KZ X X cephemCefdinir CDR, Cdn, DIN, CD, CFD X cephemCefditoren CDN X cephemCefepime FEP, Cpe, PM, CPM X X cephemCefetamet CAT, FET X cephemCefixime CFM, FIX, Cfe, IX X cephemCefmetazole CMZ, CMZS, CMT X X cephemCefonicid CID, Cfc, FON, CPO X X cephemCefoperazone CFP, Cfp, CPZ, PER, FOP,

CPX X cephem

Cefotaxime CTX, TAX, Cft, FOT, CT X X cephemCefotetan CTT, CTN, Ctn, CTE,

TANS, CNX X cephem

Cefoxitin FOX, CX, Cfx, FX X X cephemCefpodoxime CPD, Cpd, POD, PX X cephemCefprozil CPR, CPZ, FP X cephemCeftazidime CAZ, Caz, TAZ, TZ X X cephemCeftibuten CTB, TIB, CB X cephemCeftizoxime ZOX, CZX, CZ, Cz, CTZ,

TIZX X cephem

Ceftriaxone CRO, CTR, FRX, Cax, AXO, TX

X X cephem

Cefuroxime (axetil)

Cefuroxime (sodium)

CXM, CFX, ROX, Crm, FUR, XM

X

X X

cephem

Cephalexin CN, LEX, CFL X cephemCephalothin CF, Cf, CR, CL, CEP,

CE, KFX cephem

Glo

ssar

y II



Glossary II. (Continued) Antimicrobial Agent Agent

Abbreviationa


Drug Class

PO IM IVCephapirin CP, HAP X X cephemCephradine RAD, CH X cephemChloramphenicol C, CHL, CL X X phenicolCinoxacin CIN, Cn X quinoloneCiprofloxacin CIP, Cp, CI X X fluoroquinoloneClarithromycin CLR, CLM,

CLA, Cla, CHX macrolide

Clinafloxacin CFN, CLX, LF X X fluoroquinoloneClindamycin CC, CM, CD, Cd, CLI,

DAX X X lincosamide

Colistin CL, CS, CT X lipopeptideDalbavancin DAL X glycopeptideDaptomycin DAP X lipopeptideDicloxacillin DX, DIC X penicillinDirithromycin DTM, DT X macrolideDoripenem DOR X carbapenemErtapenem ETP X X carbapenemErythromycin E, ERY, EM X X macrolideFleroxacin FLE, Fle, FLX, FO X X fluoroquinoloneFosfomycin FOS, FF, FO, FM X fosfomycinGarenoxacin GRN X X quinoloneGatifloxacin GAT X X fluoroquinoloneGemifloxacin GEM X fluoroquinoloneGentamicinGentamicin synergy

GM, Gm, CN, GENGM500, HLG, Gms

X X aminoglycoside

Grepafloxacin GRX, Grx, GRE, GP X fluoroquinolone

Imipenem IPM, IMI, Imp, IP X carbapenemKanamycin K, KAN, HLK, KM X X aminoglycosideLevofloxacin LVX, Lvx,

LEV, LEVO, LEX X fluoroquinolone

Linezolid LNZ, LZ, LZD X X oxazolidinoneLomefloxacin LOM, Lmf X fluoroquinoloneLoracarbef LOR, Lor, LO X cephemMecillinam MEC X penicillinMeropenem MEM, Mer, MERO,

MRP, MPX carbapenem

Methicillin DP, MET, ME, SC X X penicillinMezlocillin MZ, Mz, MEZ X X penicillinMinocycline MI, MIN, Min, MN,

MNO, MC, MHX X tetracycline

Moxalactam MOX X X cephemMoxifloxacin MXF X X fluoroquinoloneNafcillin NF, NAF, Naf X X penicillinNalidixic acid NA, NAL X quinoloneNetilmicin NET, Nt, NC X X aminoglycosideNitrofurantoin F/M, FD, Fd, FT,

NIT, NI, FX nitrofurantoin

Norfloxacin NOR, Nxn, NX X fluoroquinoloneOfloxacin OFX, OFL, Ofl, OF X X X fluoroquinoloneOritavancin ORI X glycopeptideOxacillin OX, Ox, OXS, OXA X X X penicillin


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a Abbreviations assigned to one or more diagnostic products in the U.S.b As available in the U.S.

PO per OS (oral)IM intramuscularIV intravenous


Glossary II. (Continued)Antimicrobial Agent Agent

Abbreviationa


Drug Class

PO IM IVPenicillin P, PEN, PV X X X penicillin Piperacillin PIP, PI, PP, Pi X X penicillin Piperacillin-tazobactam TZP, PTZ, P/T, PTc X β-lactam/β-lactamase

inhibitor combinationPolymyxin B PB X lipopeptide

Quinupristin-dalfopristin SYN, Syn, QDA,RP

X streptogramin

Rifampin RA, RIF, Rif, RI,RD

X X ansamycin

Sparfloxacin SPX, Sfx, SPA, SO X fluoroquinolone

Spectinomycin SPT, SPE, SC X X aminocyclitolStreptomycin

Streptomycin synergy

S, STR,StS, SM,

ST2000, HLS

X X aminoglycoside

Sulfonamides SSS, S3 X X folate pathway antagonist(some PO only)

Teicoplanin TEC, TPN, Tei,TEI, TP, TPL

X X glycopeptide

Telavancin TLV X glycopeptideTelithromycin TEL X ketolideTetracycline TE, Te, TET, TC X X tetracyclineTicarcillin TIC, TC, TI, Ti X X penicillinTicarcillin-clavulanic acid TIM, Tim, T/C,

TCC, TLcX β-lactam/β-lactamase

inhibitorTigecycline TGC X glycylcyclineTobramycin NN, TM, TO, To,

TOBX X aminoglycoside

Trimethoprim TMP, T, TR, W X folate pathway inhibitorTrimethoprim-sulfamethoxazole

SXT, SxT, T/S, TS,COT

X X folate pathway inhibitor

Trospectinomycin X X aminocyclitolTrovafloxacin TVA, Tva, TRV, TV X X fluoroquinolone

Vancomycin VA, Va, VAN X X glycopeptide



Agent Abbreviation Antimicrobial Agents for Which RespectiveAbbreviation is Used

AZM Azithromycin, AztreonamAZ Azithromycin, Azlocillin

CB, Cb Ceftibuten, CarbenicillinCFR, Cfr Cefaclor, Cefadroxil

CF, Cf Cefaclor, CephalothinCM Clindamycin, Cefamandole

CFM, Cfm Cefixime, CefamandoleCZ, Cz Ceftizoxime, CefazolinCD, Cd Clindamycin, Cefdinir

CPZ Cefprozil, CefoperazoneCP, Cp Cephapirin, Cefoperazone, CiprofloxacinCN, Cn Cephalexin, Cefotetan, Cinoxacin, Gentamicin

CFX, Cfx Cefoxitin, CefuroximeCL Cephalothin, ChloramphenicolCH Clarithromycin, CephradineDX Doxycycline, DicloxacillinFO Fleroxacin, FosfomycinSC Spectinomycin, MethicillinSO Sparfloxacin, OxacillinTC Tetracycline, Ticarcillin

List of Identical Abbreviations Used for More Than One Antimicrobial Agent inU.S. Diagnostic Products

Iden

tical

Abb

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Summary of Comments and Subcommittee Responses

M100-S14: Performance Standards for Antimicrobial Susceptibility Testing; Fourteenth InformationalSupplement (M7—MIC Testing)

General

1. It has come to my attention that there are conflicting guidelines regarding interpretation of MICs which couldresult in confusion and subsequent mistreatment, harm, and even death of patients. For example, currentCLSI/NCCLS guidelines for vancomycin susceptibility state that the organism is resistant with an MIC >1.0 ifit is a streptococcus but sensitive up to an MIC of 4.0 if it is a staphylococcus. Clearly, any organism, staph orstrep, with an MIC <5 would be inhibited by vancomycin in a patient with therapeutic levels. Current guidelinescould result in inappropriate isolation and treatment of many patients with certain strep infections. Clearly,MIC interpretations should be based more on expected tissue and serum drug concentrations.

• CLSI/NCCLS interpretive criteria are established using a combination of microbiologic (e.g., populationdistribution data), pharmacokinetic/pharmacodynamic, and clinical response data. A drug can havedifferent levels of activity against one genus versus another for several reasons, among which are thelocation of the target site in the cell, the accessibility of the drug to the target site, and whether the drugexhibits cidal or static activity. Because of this, there are no universal breakpoints that are appropriatefor all organisms. In addition, when there is no known resistance to a particular drug, the susceptiblebreakpoint is usually set just above the upper MIC range of the normal or wild type population so thatemerging resistant populations can be detected. For example, the MICs of vancomycin for the wild typepopulation of streptococci are less than 1 µg/mL, whereas the wild type population of staphylococciincludes strains with vancomycin MICs of 2 or 4 µg/ml. Therefore, the susceptible vancomycinbreakpoint has been set at 1 µg/mL for streptococci and 4 µg/ml for staphylococci. If strains ofstreptococci were to develop vancomycin MICs >1 µg/mL, then it would be appropriate to thenreevaluate clinical and microbiological data and possibly adjust the interpretive criteria.

2. Amoxicillin-sulbactam is marketed and prescribed in more than 20 countries all over the world. The breakpointscannot be extrapolated from the results of amoxicillin-clavulanate or ampicillin-sulbactam, even though crosssusceptibility among these drugs does exist. We feel that this point should be clarified in CLSI/NCCLSrecommendations.

• Clinical and Laboratory Standards Institute is able to establish interpretive criteria only forantimicrobial agents which have been presented and discussed at CLSI meetings. If sufficient dataconforming to CLSI/NCCLS document M23—Development of In Vitro Susceptibility Testing Criteria andQuality Control Parameters for amoxicillin-sulbactam were presented to the subcommittee, we wouldconsider a request for interpretive criteria for that compound.

3. Sodium fosfomycin (not trometamol) is commonly used in Latin America for the treatment of severalinfections. Seven Latin American countries use cefoperazone-sulbactam for severe infections. No breakpointsare available for either compound.

• There are breakpoints in the current documents for Enterococcus faecalis and Escherichia coli for oralfosfomycin. If sufficient data conforming to CLSI/NCCLS document M23—Development of In VitroSusceptibility Testing Criteria and Quality Control Parameters for sodium fosfomycin and forcefoperazone-sulbactam were presented to the subcommittee, we would consider a request forinterpretive criteria for those compounds.

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Table 2A

4. In South America, azithromycin (AZ) is at present largely used for the treatment of bacterial gastroenteritis dueto Salmonella spp. or Shigella spp. Breakpoints for the assay of AZ against these isolates should be included.

• If data conforming to CLSI/NCCLS document M23—Development of In Vitro Susceptibility TestingCriteria and Quality Control Parameters are presented to the subcommittee, we would consider addinginterpretive criteria for azithromycin for these organisms.

5. In South America, ESBLs are frequently found in Proteus mirabilis, Salmonella (non-typhi) and Shigella spp.Why does Clinical and Laboratory Standards Institute consider only E. coli and Klebsiella spp. for ESBLdetection? Use of cefotaxime, ceftazidime and cefepime should be encouraged for the phenotypic detection ofESBLs.

• We have recently carried out a study to determine the suitability of the ESBL screening and confirmationtests for P. mirabilis and that organism has been added to the ESBL table in Table 2A in M2 and M7 alongwith E. coli, K. pneumoniae, and K. oxytoca. Although the use of cefepime for characterizing ESBLs hasbeen described, criteria for the use of cefepime with and without clavulanate has not been studiedsufficiently to date to be included in the document. The same is true for Salmonella and Shigella spp.,which precludes adding them to the list at this time.

Table 2C

6. We currently do not perform any definitive identification testing on any coagulase-negative staphylococci(CoNS). We do a rapid latex, and if negative, report as CoNS. In M100-S14, the text states that testing for mecAor PBP 2a is to be performed on non-S. epidermidis isolates. Are you then saying that I must now performdefinitive identification for all coagulase-negative staphylococci?

• The Clinical and Laboratory Standards Institute does not require identification of coagulase-negativestaphylococci to the species level, with two exceptions: 1) laboratories should identify S. saprophyticus inurinary isolates for which susceptibility testing is not recommended; and 2) laboratories should identifyS. lugdunensis, an uncommon pathogen, but one that can cause endocarditis. For laboratories that do notwish to identify all coagulase-negative staphylococci to species level, S. saprophyticus and S. lugdunensiscan be easily identified using a few simple tests (Clinical Microbiology Procedures Handbook, 2nd edition,2004, ASM Press; Manual of Clinical Microbiology, 8th edition 2003, ASM Press). S. saprophyticus isnovobiocin resistant at ≤≤ 16 mm on Mueller-Hinton agar. S. lugdunensis can be identified usingpyrrolidonyl arylamidase and ornithine decarboxylase. S. lugdunensis is strongly PYR positive andornithine decarboxylase positive. A simple scheme for identification of S. lugdunensis has also beenproposed by Schnitzler, et al. (J Clin Microbiol, 36:812-13;1998).

7. If we have a patient with pure culture of coagulase-negative staphylococci from a lower respiratory specimen,a wound, or a catheter tip, are you suggesting that because these are not sterile sites, we should not beperforming the mecA testing? Is this mecA test ONLY for sterile site specimens, or is it for serious infectionsand sites? You know that a terminology of “serious infection” falls into a gray zone.

• The definition of serious infection should be institution-specific. Laboratories, in consultation withinfectious disease clinicians, should decide which specimens warrant additional testing of CoNS for mecAor PBP 2a. For example, isolates from endocarditis and osteomyelitis would fall into this category.

8. I have a question regarding the use of the cefoxitin disk to predict for oxacillin resistance in Staphylococcusspecies as outlined in M100-S14. The following two statements in the document are in themselves easilyunderstood.

M100-S14, page 104, Warning 2, states, “For oxacillin-resistant Staphylococcus aureus and coagulase-negativestaphylococci, all penicillins, cephems, and other ß-lactams...may appear active in vitro but are not effectiveclinically. Results for these drugs should be reported as resistant or should not be reported.” C

omm

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MIC



M100-S14, page 105, comment 10, states, “For oxacillin-susceptible strains, results for parenteral and oralcephems, ß-lactam/ß-lactamase inhibitor combinations, and carbapenems, if tested, should be reportedaccording to the results generated using routine interpretative criteria.”

It is when I attempt to combine the information that I am becoming confused.

Let’s say that I have a Staphylococcus species with MICs for oxacillin and cefazolin which interpret as resistant,but the cefoxitin disk diffusion interpretation is susceptible. Do I change the cephems, and other ß-lactams tosusceptible as well, following the logic of page 104, warning 2, or do I leave the cephems and other ß-lactamsas resistant in accordance with comment 10 on page 105?

• Testing of staphylococci against cefazolin and cefoxitin using an MIC method is not recommended.Determination of oxacillin susceptibility is best done with oxacillin when using an MIC method and bycefoxitin when doing disk diffusion. These phenotypic test methods correlate best with the presence orabsence of the mecA gene, which is associated with oxacillin resistance. Susceptibility to cefazolin andother cephems should be predicted using oxacillin when performing an MIC test or cefoxitin (foroxacillin) when performing disk diffusion.

9. If I were to not perform any definitive identification on coagulase-negative staphylococci isolates andperformed the mecA test, what are the implications if the isolate was truly an S. epidermidis?

• Tests for mecA and the gene product PBP 2a are accurate and rapid methods for detecting oxacillinresistance in S. aureus and coagulase-negative staphylococci including S. epidermidis.

10. In Table 2C (M7), comment 10, is this mecA testing for coagulase-negative staphylococci isolates only, or is italso for S. aureus?

• See the response to comment 9.

11. I have a question regarding the testing of coagulase-negative staphylococci isolates with cefoxitin. We use anautomated system and this particular drug is not on the conventional panel that we test. Dropping a disk wouldinvolve keeping Mueller-Hinton agar on hand and performing QC on the disks. Is this testing for sterile sitesonly? Is this a rule or just a recommendation? We would appreciate any guidance on this matter.

• Determination of oxacillin susceptibility is best done with oxacillin when using an MIC method and bycefoxitin when performing disk diffusion. These phenotypic test methods correlate best with the presenceor absence of the mecA gene, which mediates oxacillin resistance. When using an automated system, avalidation study should be performed prior to routine use to determine if it accurately predicts oxacillinsusceptibility.

12. Why is Clinical and Laboratory Standards Institute moving to the cefoxitin disk screen test for oxacillinresistance detection in staphylococci? It is clear that there is better correlation between oxacillin resistance andmecA detection or the latex test for PBP 2a. This information should be stated in the CLSI recommendations.

• For S. aureus and S. lugdunensis, the cefoxitin disk test is comparable to the oxacillin disk test forprediction of mecA-mediated resistance to oxacillin; however, the cefoxitin disk test is easier to read andtherefore it is the preferred method. For coagulase-negative staphylococci, oxacillin interpretive criteriacorrelate with the presence or absence of the gene encoding oxacillin resistance (mecA) in S. epidermidis;however, these interpretive criteria may overcall resistance for other coagulase-negative staphylococci(e.g., S. saprophyticus). For coagulase-negative staphylococci, the cefoxitin disk test has greater specificitythan oxacillin and equal sensitivity, although it may miss some strains of mecA-positive S. simulans. It istrue, however, that mecA detection and the latex test for PBP 2a are the most accurate predictors ofmecA-mediated resistance and these tests should be used when available and clinically relevant. However,not all laboratories have the resources to perform these tests. Please also see the response to comment 11.

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Vol. 25 No. 1 M100-S15

Related CLSI/NCCLS Publications*

M2-A8 Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard—Eighth Edition (2003).This standard contains updated recommended techniques, interpretive criteria, and quality control parameters for disk susceptibility testing.

M7-A6 Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; ApprovedStandard—Sixth Edition (2003). This standard provides updated reference methods for the determination of minimalinhibitory concentrations (MICs) for aerobic bacteria by broth macrodilution, broth microdilution, and agar dilution.

M11-A6 Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard—Sixth Edition(2004). This standard provides reference methods for the determination of minimal inhibitory concentrations (MICs)of anaerobic bacteria by broth microdilution and agar dilution.

M23-A2 Development of In Vitro Susceptibility Testing Criteria and Quality Control Parameters; Approved Guideline—Second Edition (2001). This document addresses the required and recommended data needed for the selection ofappropriate interpretive standards and quality control guidelines for antimicrobial agents.

M31-A2 Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated fromAnimals; Approved Standard—Second Edition (2002). This document provides the currently recommendedtechniques for antimicrobial agent disk and dilution susceptibility testing, criteria for quality control testing, andinterpretive criteria for veterinary use.

M37-A2 Development of In Vitro Susceptibility Testing Criteria and Quality Control Parameters for VeterinaryAntimicrobial Agents; Approved Guideline—Second Edition (2002). This document addresses the required andrecommended data needed for selection of appropriate interpretative standards and quality control guidance for newveterinary antimicrobial agents.

M39-A Analysis and Presentation of Cumulative Antimicrobial Susceptibility Test Data; Approved Guideline (2002).This document describes methods for the recording and analysis of antimicrobial susceptibility test data, consisting ofcumulative and ongoing summaries of susceptibility patterns of epidemiologically significant microorganisms.

_____________* Proposed- and tentative-level documents are being advanced through the Clinical and Laboratory Standards Institute consensusprocess; therefore, readers should refer to the most recent editions.



NOTES

Vol. 25 No. 1 M100-S15


NOTES



NOTES

Vol. 25 No. 1 M100-S15


NOTES

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LaboratoriesRiverside Medical Center (IL)Robert Wood Johnson University

Hospital (NJ)Royal Columbian Hospital (New

Westminster, BC, Canada)Sahlgrenska Universitetssjukhuset

(Sweden)St. Alexius Medical Center (ND)St. Anthony Hospital (CO)St. Anthony's Hospital (FL)St. Barnabas Medical Center (NJ)St. Christopher's Hospital for

Children (PA)St-Eustache Hospital (Quebec,

Canada)St. John Hospital and Medical

Center (MI)St. John's Hospital & Health Center

(CA)St. Joseph Mercy Hospital (MI)St. Joseph's Hospital - Marshfield

Clinic (WI)St. Jude Children's Research Hospital

(TN)St. Mary of the Plains Hospital

(TX)St. Michael's Hospital (Toronto,

ON, Canada)Ste. Justine Hospital (Montreal, PQ,

Canada)Salem Clinic (OR)San Francisco General Hospital

(CA)Santa Clara Valley Medical Center

(CA)Seoul Nat'l University Hospital

(Korea)Shands at the University of FloridaSouth Bend Medical Foundation

(IN)South Western Area Pathology

Service (Australia)Southern Maine Medical Center Spartanburg Regional Medical

Center (SC)Specialty Laboratories, Inc. (CA)State of Connecticut Dept. of Public

HealthState of Washington Department of

HealthStony Brook University Hospital

(NY)Stormont-Vail Regional Medical

Center (KS)Sun Health-Boswell Hospital (AZ)Sunnybrook Health Science Center

(ON, Canada)Sunrise Hospital and Medical Center

(NV)

Swedish Medical Center - Providence Campus (WA)

Temple University Hospital (PA)Tenet Odessa Regional Hospital

(TX)The Toledo Hospital (OH)Touro Infirmary (LA)Tripler Army Medical Center (HI)Truman Medical Center (MO)UCLA Medical Center (CA)UCSF Medical Center (CA)UNC Hospitals (NC)Unidad de Patologia Clinica (Mexico)Union Clinical Laboratory (Taiwan)Universita Campus Bio-Medico

(Italy)University College Hospital (Galway,

Ireland)University of Alabama-Birmingham

Hospital University of Chicago Hospitals

(IL)University of Colorado HospitalUniversity of Debrecen Medical Health and Science Center (Hungary)University of Illinois Medical CenterUniversity of Maryland Medical

SystemUniversity of the Ryukyus (Japan)University of Wisconsin HospitalThe University of Texas Medical

BranchThe University of the West IndiesUniversity of Virginia Medical

CenterUniversity of WashingtonUSA MEDDAC-AKUS LABS, Inc. (CA)UZ-KUL Medical Center (Belgium)VA (Hampton) Medical Center (VA)VA (Tuskegee) Medical Center

(AL) Valley Children's Hospital (CA)Virginia Beach General Hospital

(VA)Virginia Department of HealthVirginia Regional Medical Center

(MN)ViroMed Laboratories (MN)Washington Adventist Hospital

(MD)Washoe Medical Center

Laboratory (NV)Waterford Regional Hospital

(Ireland)Wellstar Health Systems (GA)West Jefferson Medical Center (LA)Wilford Hall Medical Center (TX)William Beaumont Army Medical

Center (TX)William Beaumont Hospital (MI)William Osler Health Centre (Brampton,

ON, Canada)Winn Army Community Hospital

(GA)Winnipeg Regional Health Authority

(Winnipeg, Canada)Wishard Memorial Hospital (IN)Yonsei University College of

Medicine (Korea)York Hospital (PA)

OFFICERS BOARD OF DIRECTORS

Thomas L. Hearn, Ph.D.,President

Centers for Disease Control and Prevention

Robert L. Habig, Ph.D.,President-Elect

Abbott Laboratories

Wayne Brinster,Secretary

BD

Gerald A. Hoeltge, M.D.,Treasurer

The Cleveland Clinic Foundation

Donna M. Meyer, Ph.D.,Immediate Past President

CHRISTUS Health

Glen Fine, M.S., M.B.A., Executive Vice President

Susan Blonshine, RRT, RPFT, FAARCTechEd

Kurt H. Davis, FCSMLS, CAECanadian Society for Medical Laboratory Science

Mary Lou Gantzer, Ph.D.Dade Behring Inc.

Lillian J. Gill, M.S.FDA Center for Devices and Radiological Health

Carolyn D. Jones, J.D., M.P.H.AdvaMed

J. Stephen Kroger, M.D., MACPCOLA

Willie E. May, Ph.D.National Institute of Standards and Technology

Gary L. Myers, Ph.D.Centers for Disease Control and Prevention

Klaus E. Stinshoff, Dr.rer.nat.Digene (Switzerland) Sàrl

James A. ThomasASTM International

Kiyoaki Watanabe, M.D.Keio University School of Medicine

Judith A. Yost, M.A., M.T.(ASCP)Centers for Medicare & Medicaid Services

940 West Valley Road Suite 1400 Wayne, PA 19087 USA Phone 610.688.0100 FAX 610.688.0700 E-MAIL: [email protected] WEBSITE: www.clsi.org ISBN 1-56238-556-9

manual clsi 2005

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