Vikas Kesarwani Vikas Kesarwani MD FICM FCCPMD FICM FCCPAsstt. Professor & In-charge, Asstt. Professor & In-charge,

Department of Critical care medicineDepartment of Critical care medicine

ANTIMICROBIAL STEWARDSHIP:ANTIMICROBIAL STEWARDSHIP:A CONCERN FOR ALL PRACTITIONERSA CONCERN FOR ALL PRACTITIONERS

Guideline ResourcesGuideline Resources

• IDSA and SHEAIDSA and SHEA– Guidelines for Developing an Institutional Program Guidelines for Developing an Institutional Program

to Enhance Antimicrobial Stewardshipto Enhance Antimicrobial Stewardship

• ASMASM– Antimicrobial Resistance Prevention Initiative—An Antimicrobial Resistance Prevention Initiative—An

UpdateUpdate

IDSA: Infectious Disease Society of America IDSA: Infectious Disease Society of America SHEA: Society of Heathcare Epidemiology of AmericaSHEA: Society of Heathcare Epidemiology of AmericaASM: American Society of Microbiology ASM: American Society of Microbiology

Appropriate initial antibioticAppropriate initial antibiotic (usually empirical)(usually empirical) while while improving improving patient patient

outcomesoutcomes and and heathcare heathcare

Appropriate initial antibioticAppropriate initial antibiotic (usually empirical)(usually empirical) while while improving improving patient patient

outcomesoutcomes and and heathcare heathcare

UnnecessaryUnnecessaryAntibioticsAntibiotics (broad (broad

spectrum) and increased spectrum) and increased resistanceresistance and and costcost

UnnecessaryUnnecessaryAntibioticsAntibiotics (broad (broad

spectrum) and increased spectrum) and increased resistanceresistance and and costcost

Antimicrobial Therapy : Antimicrobial Therapy :

Anti-Anti-MicrobialMicrobial

StewardshipStewardship

A Balancing ActA Balancing Act

Why Stewardship is Needed

– Up to Up to 50% antimicrobial 50% antimicrobial prescribingprescribing inappropriate inappropriate**

– Causal relationshipCausal relationship between between antimicrobial useantimicrobial use and and emergence of emergence of resistanceresistance

– IDSA’s: IDSA’s: Bad Bugs, No Drugs task forceBad Bugs, No Drugs task force to call for to call for a global commitment from stakeholders to support a global commitment from stakeholders to support the the development of 10 new drugs in development of 10 new drugs in novelnovel classes classes by the year 2020by the year 2020: : 10 × 20 initiative10 × 20 initiative

*Dellit TH et al. IDSA and SHEA guidelines. Clin inf dis 2007;44(2):159-177.IDSA: Infectious Diseases Society of America

Those of us not developing new drugs Those of us not developing new drugs have another job: have another job:

Conserve the antibiotics byConserve the antibiotics by Antibiotic stewardship Antibiotic stewardship

What is Antimicrobial Stewardship?What is Antimicrobial Stewardship?

• ““The optimal The optimal selectionselection, , dosagedosage, and , and durationduration of of antimicrobial treatmentantimicrobial treatment that that results in the results in the best clinical outcome”best clinical outcome” or or

““TreatmentTreatment and and prevention of infectionprevention of infection, , with with minimal toxicityminimal toxicity to the patient and to the patient and minimal impactminimal impact on subsequent on subsequent resistanceresistance.”.”

Dellit TH, et al. CID 2007;44:159-77, Dellit TH, et al. CID 2007;44:159-77, Hand K, et al. Hospital Pharmacist 2004;11:459-64Hand K, et al. Hospital Pharmacist 2004;11:459-64Paskovaty A, et al IJAA 2005;25:1-10Paskovaty A, et al IJAA 2005;25:1-10

3 Goals of Antimicrobial Stewardship3 Goals of Antimicrobial Stewardship

• 11stst Goal: Goal: each patient receive the most each patient receive the most appropriateappropriate antimicrobial antimicrobial

• 2nd Goal:2nd Goal: preventprevent antimicrobial antimicrobial overuse, misuse, and abuse.overuse, misuse, and abuse.

• 3rd Goal :3rd Goal : minimize minimize the development ofthe development of resistance.resistance.

• Secondary goalSecondary goalReduceReduce healthcare healthcare costscosts without adversely impacting without adversely impacting

quality of carequality of care

Goals of Antimicrobial StewardshipGoals of Antimicrobial Stewardship

11stst Goal: Goal: each patient receive the most each patient receive the most appropriate antimicrobial appropriate antimicrobial

““4 D’s4 D’s of optimal antimicrobial therapy”: of optimal antimicrobial therapy”:

- - RightRight Drug Drug,,--RightRight DoseDose, , - - De-escalationDe-escalation to pathogen-directed therapy, to pathogen-directed therapy,- - RightRight DurationDuration of therapy. of therapy.

Goals of Antimicrobial StewardshipGoals of Antimicrobial Stewardship

• 22ndnd Goal: prevent antimicrobial Goal: prevent antimicrobial overuse, misuse, and abuse.overuse, misuse, and abuse.

Overuse:Overuse:Antibiotics toAntibiotics to patients with patients with viral infectionsviral infections, , noninfectious processes (noninfectious processes (pancreatitispancreatitis), infections ), infections that do not require antibiotics (that do not require antibiotics (small skin abscesses small skin abscesses that willthat will resolve with I & D resolve with I & D), and ), and bacterial colonizationbacterial colonization (positive urine culture result in (positive urine culture result in catheterized patient.).catheterized patient.).

Goals of Antimicrobial StewardshipGoals of Antimicrobial Stewardship• 22ndnd Goal: prevent antimicrobial Goal: prevent antimicrobial

overuse, misuse, and abuse.overuse, misuse, and abuse.

• Misuse: Misuse: use of use of broad-spectrum antibioticsbroad-spectrum antibiotics that cover that cover MDR organisms in a patient with MDR organisms in a patient with community acquiredcommunity acquired infectioninfection or the or the failure to adjust antibiotics according failure to adjust antibiotics according to culture.to culture.

• Abuse:Abuse: use of one use of one particular antibiotic preferentially particular antibiotic preferentially over othersover others as a result of as a result of aggressive detailing by aggressive detailing by pharmaceutical representativepharmaceutical representative or worse because or worse because of of financial interest.financial interest.

Goals of Antimicrobial StewardshipGoals of Antimicrobial Stewardship

• 33rdrd Goal : Goal : minimize minimize the development ofthe development of resistance. resistance. Antimicrobial resistance is associated with Antimicrobial resistance is associated with increased morbidity and mortalityincreased morbidity and mortality

Building the Stewardship teamBuilding the Stewardship team

Infectious Diseases Infectious Diseases SpecialistsSpecialists

AntimicrobialAntimicrobialControlControl

AntimicrobialAntimicrobialControlControl

Infection Control Infection Control AdministrationAdministration

ClinicalClinicalPharmacists Pharmacists

ID trainedID trained

NursingNursingSurgical InfectionSurgical InfectionExperts/SurgeonsExperts/Surgeons

OT PersonnelOT PersonnelMicrobiologistMicrobiologist

IntensivistIntensivist

The stewardship team does not The stewardship team does not have to fit a particular mold.have to fit a particular mold.

Building the Stewardship teamBuilding the Stewardship team

Hospitalist interested inHospitalist interested in infectious disease infectious disease

AntimicrobialAntimicrobialControlControl

AntimicrobialAntimicrobialControlControl

Infection Control Infection Control AdministrationAdministration

NursingNursingSurgical InfectionSurgical InfectionExperts/SurgeonsExperts/Surgeons

OT PersonnelOT PersonnelMicrobiologistMicrobiologist

IntensivistIntensivist

Infection Infection preventionistpreventionist

Antimicrobial Stewardship Antimicrobial Stewardship Core StrategiesCore Strategies

IDSA Grading System for Ranking IDSA Grading System for Ranking Recommendations in Clinical GuidelinesRecommendations in Clinical Guidelines

Kish MA et al. CID 2001; 32: 851 - 4Kish MA et al. CID 2001; 32: 851 - 4

Category, GradeCategory, Grade DefinitionDefinition

Strength of Strength of recommendationrecommendation AA Good evidence to supportGood evidence to support

BB Moderate evidence to supportModerate evidence to support

CC Poor evidence to supportPoor evidence to support

Quality of evidenceQuality of evidence II ≥ ≥ 1 randomized, controlled trials1 randomized, controlled trials

IIII ≥ ≥ 1 clinical trial unrandomized, cohort 1 clinical trial unrandomized, cohort or case-controlled studies, dramatic or case-controlled studies, dramatic results from uncontolled experimentsresults from uncontolled experiments

IIIIII Opinion of experts, clinical experience, Opinion of experts, clinical experience, descriptive studiesdescriptive studies

Antimicrobial Stewardship Core StrategiesAntimicrobial Stewardship Core Strategies

• Front endFront end (pre-prescription approach): (pre-prescription approach):

Formulary restrictionFormulary restriction and and preauthorizationpreauthorization (expert approval) leading to reductions in (expert approval) leading to reductions in antimicrobial use and cost . antimicrobial use and cost . (A II)(A II)

• Back endBack end (Post prescription approach): (Post prescription approach):

Interventions after antimicrobials have been Interventions after antimicrobials have been prescribedprescribed. (A II). (A II)

• Prospective audit with intervention and feedbackProspective audit with intervention and feedback of of antimicrobial use and resistance patterns antimicrobial use and resistance patterns to reduce to reduce inappropriate antimicrobial use inappropriate antimicrobial use (A I)(A I)

Dellit TH, et al. CID 2007;44:159-77 Dellit TH, et al. CID 2007;44:159-77 Hand K, et al Hospital Pharmacist 2004;11:459-64Hand K, et al Hospital Pharmacist 2004;11:459-64Paskovaty A, et al IJAA 2005;25:1-10Paskovaty A, et al IJAA 2005;25:1-10

Core strategy “The Front End”Core strategy “The Front End”

• Restrictive prescriptive authorityRestrictive prescriptive authority::

- Certain- Certain antimicrobialsantimicrobials require require prior authorizationprior authorization for use by all except a select group of clinicians.for use by all except a select group of clinicians.

- Approved- Approved for a specific for a specific durationduration, thereby , thereby prompting reviewprompting review after cultureafter culture data obtained. data obtained.

- - TargetTarget a a specific diseasespecific disease or indication with or indication with specific antimicrobialsspecific antimicrobials associated with associated with highhigh rates rates of of resistance and costresistance and cost..

Advantage:Advantage: --PreventsPrevents overuse, misuse overuse, misuse andand abuse abuse. . - Significant - Significant reduction in cost. reduction in cost.

Core Strategy “The Back end”Core Strategy “The Back end”

• Post prescription restriction: Uses prospective review and Post prescription restriction: Uses prospective review and feedback. feedback.

• Specific AntimicrobialsSpecific Antimicrobials are are reviewed at specified intervalsreviewed at specified intervals after initiation. Adviced to after initiation. Adviced to continue, adjust, change, or continue, adjust, change, or discontinuediscontinue the therapy the therapy based on microbiology resultsbased on microbiology results and and clinical featuresclinical features of the case. of the case.

AdvantageAdvantageFocus is on Focus is on De-escalation.De-escalation.- - changing a changing a broad-spectrumbroad-spectrum antibiotic to antibiotic to narrow spectrumnarrow spectrum - changing from - changing from combinationcombination therapy to therapy to monotherapymonotherapy, or, or- - stopping antibioticstopping antibiotic therapy altogether as it becomes more therapy altogether as it becomes more apparent that these drugs are apparent that these drugs are not needednot needed. .

Supplemental Antimicrobial Supplemental Antimicrobial Stewardship Strategies/TechniquesStewardship Strategies/Techniques

– Education: clinical guidelines, infection Education: clinical guidelines, infection control.control.

– Antimicrobial order formsAntimicrobial order forms

– IV-PO switchIV-PO switch

– Dose optimization via PK-PDDose optimization via PK-PD

– Antimicrobial cyclingAntimicrobial cycling

Educational StrategiesEducational Strategies

• Educational programs, active interventionEducational programs, active intervention(A-III, B-II)(A-III, B-II) Guideline & algorithm dissemination.Guideline & algorithm dissemination.

• Guidelines and clinical pathways – Guidelines and clinical pathways – seek multi-seek multi-disciplinary involvement and approvaldisciplinary involvement and approval (A-I)(A-I)– Incorporate local antimicrobial resistanceIncorporate local antimicrobial resistance patterns patterns

(A-I)(A-I)– Provide Provide education and feedbackeducation and feedback to practitioners to practitioners

(A-III)(A-III) idea ? idea ? Microbiology Newsletter.Microbiology Newsletter. Questions of the Questions of the week/monthweek/month

Antimicrobial order forms (B-II)Antimicrobial order forms (B-II)Shown to be effective component of the program Shown to be effective component of the program

and can and can facilitate planning facilitate planning into into practice. practice. Helps Helps audit audit andand feedback. feedback.

– ensures ensures guideline-basedguideline-based appropriate appropriate empiric empiric antibioticantibiotic ordering. ordering.

– Day 3 reviewDay 3 review bundlebundle based on investigations and based on investigations and clinical profile. clinical profile.

– Streamlining or Streamlining or de-escalationde-escalation therapy therapy (A-II)(A-II)

Antimicrobial order formsAntimicrobial order forms

Day 3 Antibiotic Review Bundle Day 3 Antibiotic Review Bundle

Pulcini et al, JAC, 2008 Pulcini et al, JAC, 2008

Parenteral to Enteral conversion Parenteral to Enteral conversion (A-I)(A-I)– As soon as the patient’s condition allowsAs soon as the patient’s condition allows

• Reduces length of stay Reduces length of stay && healthcare costs healthcare costs

I.V. to oral switch overI.V. to oral switch over

Dose optimization via PK-PDDose optimization via PK-PDDose optimization Dose optimization (A-II)(A-II)

Based on Based on Organ dysfunctionOrgan dysfunction..Patient characteristicsPatient characteristics (wt, age, sex, (wt, age, sex, ethnicity),ethnicity),Causative Causative organismorganism ( (virulencevirulence), ), SiteSite of infection (drug delivery to that site) of infection (drug delivery to that site)

– Hypothesis:Hypothesis: by by removing specific classesremoving specific classes of of antimicrobials antimicrobials on a regular basison a regular basis, the , the development of resistance can be avoided.development of resistance can be avoided.

Antimicrobial cycling – is Antimicrobial cycling – is not recommended not recommended because of because of insufficient datainsufficient data (no ranking) (no ranking)

Antimicrobial cyclingAntimicrobial cycling

………………………………….

Barriers to Implementing Antibiotic Barriers to Implementing Antibiotic stewardship programmestewardship programme

The Vicious Spiral: The Prescriber’s dilemma

--Must get right at all Must get right at all cost.cost.

-Blanket cover is less -Blanket cover is less stressful. stressful.

-Lack of faith in tests-Lack of faith in tests

-Defensive medicine-Defensive medicine

use of new use of new drugsdrugs

Use of broad Use of broad spectrum drugs spectrum drugs C.difficleC.difficle

costcostResistanceResistance

Barriers to Implementing Antibiotic Barriers to Implementing Antibiotic stewardship programmestewardship programme

Lack of understanding of problem…Who cares..Lack of understanding of problem…Who cares..– Staff may not want to assume “added” Staff may not want to assume “added”

responsibility. responsibility. (No compensation)(No compensation)..– The paradoxThe paradox: : higherhigher the the antibiotic demandantibiotic demand more more

earning, earning, happierhappier the the beneficiariesbeneficiaries. .

– ““Many Many clinicians might feel offendedclinicians might feel offended to their right to their right to prescribe antibiotics freely (unrestricted)”to prescribe antibiotics freely (unrestricted)”

-Sunenshine RH, et al. -Sunenshine RH, et al. Clin Infect Dis Clin Infect Dis 2004;38:934-38.2004;38:934-38.

-Arvind Kejriwal-Arvind Kejriwal IAC IAC

We can still do much without problem.

Every ounce of stewardship counts Every ounce of stewardship counts

– start small, – start small, think bigthink big!!

We can still do a lot….. We can still do a lot…..

• Form an Form an Antibiotic stewardship teamAntibiotic stewardship team with with Hospitalists interested in infectious Hospitalists interested in infectious diseasedisease..

• Educate:Educate: clinical guidelines, algorithms, clinical guidelines, algorithms, infection control techniques.infection control techniques.

• Day 3 Antibiotic Review form.Day 3 Antibiotic Review form.

Day 3 Antibiotic Review form

Pulcini et al, JAC, 2008

-IV-PO switch.IV-PO switch.-De-escalation.De-escalation.-Audit and feedback.Audit and feedback.

We can still do a lot….. We can still do a lot…..

• Form an Form an Antibiotic stewardship teamAntibiotic stewardship team with with Hospitalists interested in infectious diseaseHospitalists interested in infectious disease..

• Educate:Educate: clinical guidelines, algorithms, infection clinical guidelines, algorithms, infection control techniques.control techniques.

• Day 3 Antibiotic Review form.Day 3 Antibiotic Review form. - - IV-PO switch.IV-PO switch.- De-escalation.- De-escalation.- Audit and feedback.- Audit and feedback.

• PosterPoster of of empiric treatment guidelineempiric treatment guideline. . • Microbiology newsletterMicrobiology newsletter with microbial resistance with microbial resistance

review and feedback. review and feedback.

………………………….

A Disturbing Trend

1930 1940 1950 1960 1970 1980 1990 2000 2010

Sulfa, BL, AG, Chloramphenicol

TCN, MAC, Vanc, RIF, FQ, TMP

No new classes. Modification of existing agents.

LZD, DAP,TIG

CBP; DAL;New Entities

Limited

PCN-resistant S. aureus

MRSA

VRE

VISA in 7 states

VRSA

LZD-R S. aureus

MDR Pseudomonas and Acinetobacter, metallo-beta-lactamases, carbapenemases

Half of US and Japanese companies END drug discovery

Computer Surveillance

• Sentri7• SafetySurveillor-Pharmacy• TheraDoc• CPOE• Benchmarking• Antimicrobial use