Practical Aspects of Control of Multidrug Resistant Organisms (MDROs)

Hospital Authority Convention 2012 May 7, 2012

Tom R. Talbot, MD MPH Associate Professor of Medicine and Preventive Medicine

Vanderbilt University School of Medicine Chief Hospital Epidemiologist

Vanderbilt University Medical Center

Objectives • Describe the most common types of MDROs and

their epidemiology • Discuss interventions designed to prevent the

transmission of MDROs in healthcare settings

• Discuss some practical challenges with implementing these interventions for MDRO control

Multidrug-Resistant Organisms (MDROs): Background

• Infectious agents that are resistant to key antimicrobials. May include resistance to: – One or more antimicrobials – All but one antimicrobial or class – All antimicrobials and classes – Three or more antimicrobial classes*

• Limited treatment options • Associated morbidity/mortality

*Management of MDRO in Healthcare Settings, 2006 HICPAC

S = Sensitive (Antibiotic will treat) R = Resistant (Antibiotic will NOT treat)

Different Antibiotic Options

MDR GN

What options do we have to treat this patient?

Examples of MDROs

• Methicillin-resistant Staphylococcus aureus • Vancomycin-resistant Enterococci • MDR Gram-negative bacilli

– Carbepenemase-resistant Enterobacteriaceae (CRE) – New Delhi metallo-β-lactamase (NDM-1)

• Clostridium difficile*

MRSA

VRE

MDR GN

C diff

*Often grouped with MDROs but not technically MDRO;

Will not be covered in this lecture

MRSA • Staphylococcus aureus resistant to methicillin/oxacillin • Illness ranges from very minor to life-threatening • Causes increased morbidity and mortality • Has emerged in community (soft tissue infections) • Persons may be colonized (nares, skin) or infected

Gorwitz RJ et al. Journal of Infectious Diseases. 2008: 197:1226-34

Klevens MR et al JAMA 2007;298:1763+

Invasive MRSA Incidence

94,360 MRSA Deaths

MRSA

VRE • Enterococcus species that is resistant to vancomycin

– Endemic in most US hospitals – Asymptomatic carriage can occur (GI tract) – Illness ranges from very minor to life-threatening – Associated with increased morbidity and mortality as

compared with infection due to susceptible enterococci

– Includes E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii

– Mechanisms of Resistance • Chromosomally-mediated:

– AmpC type β-lactamases

• Plasmid-mediated: – Extended-spectrum-β-lactamases (ESBLs) – Carbapenemases (e.g. KPCs) – New Delhi metallo-β-lactamase (NDM-1)

• Integron-mediated: – Verona integron-encoded metallo-β-lactamases (VIM)

MDR Gram Negatives

• Klebsiella pneumoniae carbapenemases (KPCs) – A type of CRE – Confers resistance to all β-lactams – Resides on transferable plasmids and hydrolyzes all penicillins,

cephalosporins and carbapenems – Limits options for treatment

MDR Gram Negatives

Schwaber MJ et al JAMA 2008;300:2911

Gupta N et al Clin Infect Dis 2011;53:60+

New Delhi Metallo-β-Lactamase (NDM-1)

MDR GN

Antibiotic Resistance: Healthcare-Associated Infections (HAIs) in USA

MDROs accounted for 16% of all reported US HAIs in 2007

Hidron AI et al. Infect Control Hosp Epidemiol 2008:29:996+

Gupta N et al Clin Infect Dis 2011;53:60+

MDR GN

http://ecdc.europa.eu/en/activities/surveillance/EARS-Net/database/Pages/map_reports.aspx

MRSA VRE

Ps Ag R to Carbapenems

2010

Kp R to Carbapenems

http://www.chp.gov.hk/en/epidemiology/29/97/119/564.html

Clinical Impact of MDROs • Limited treatment options • Propensity for transmission within healthcare

facilities • Worse outcomes (APACHE II scores, length of

stay, mortality) shown for most

ALL MDROs

Cosgrove SE et al Clin Infect Dis 2003;36:53+

MRSA and Mortality: Bacteremia

MRSA

Engemann JJ et al CID 2003;36:592+

MRSA and Mortality: Surgical Site Infections

MRSA

Mortality Associated with KPC-Producing Organisms

p<0.001

p<0.001

20 48 12 38

OR 3.71 (1.97-7.01) OR 4.5 (2.16-9.35)

Patel et al. Infect Control Hosp Epidemiol 2008;29:1099-1106

MDR GN

Source of the MDRO • Colonized or infected patient • Colonized or infected healthcare worker • Contaminated environment • Spontaneous mutation

ALL MDROs

Crnich CJ et al Resp Care 2005,50:813+

Environmental Contamination ALL MDROs

Reducing Transmission of MDROs in Healthcare Settings

• Administrative measures and adherence monitoring • Education and training of healthcare personnel • Surveillance (know the scope of the problem) • Infection control precautions • Environmental measures • Judicious use of antimicrobial agents

ALL MDROs

*Management of MDRO in Healthcare Settings, 2006 HICPAC

www.PreventingHAIs.com

MRSA

MDR GN

CDC Transmission-Based Precautions

• Based upon the mode of spread of the pathogen • Hand hygiene • Involves use of personal protective equipment

ALL MDROs

Practical Challenges with Improving Hand Hygiene

• Involves creating reflexive behavior in all healthcare workers

• Must be accessible during workflow • Must be emphasized as priority • Must have accountability related to performance

ALL MDROs

Contact Precautions • Used w/ pathogens transmitted by direct contact • Gloves & gown upon entering pt room

ALL MDROs

Practical Challenges with Use of Isolation Precautions

• Also involves behavior change • Perceptions of

– Importance of PPE in breaking transmission – Individual role in transmission – Effectiveness of precautions

• Does not replace hand hygiene • Unanticipated consequences of isolation

precautions • How to apply to non-acute care settings?

ALL MDROs

Contamination of Gowns, Gloves and Hands

Morgan, D, et al. Infect Control Hosp Epidemiol. 2010;31:716+

MDR GN

Diekema D et al CID 2007;44:1101+

Adverse Consequences of Contact Precautions

Decreased healthcare contacts

Patients examined less frequently each day

Patients have vital signs checked less often

More adverse events

Psychological symptoms (depression)

ALL MDROs

General Recommendations: Environmental Measures

• Clean and disinfect surfaces in close proximity to patient and high-touch surfaces more frequently than minimal-touch surfaces

• Dedicate non-critical equipment to use on individual patients colonized or infected with MDROs

• Prioritize room cleaning of patients on contact precautions

*Management of MDRO in Healthcare Settings, 2006 HICPAC

ALL MDROs

Practical Challenges with Environmental Interventions

• Cleaning of critical equipment – Who cleans the ventilator, bedside IV pump? – Fear that untrained staff will do harm – Trained staff often too busy to clean

• How do you audit cleanliness? – New technologies – Resource investment

ALL MDROs

Auditing Environmental Cleanliness

• ATP Detection – Swab detection of ATP

on surfaces (as marker of organism burden)

• Fluorescent tags – High touch surfaces – Place and return after

cleaning to assess

ALL MDROs

Judicious Use of Antimicrobial Agents/ Antimicrobial Stewardship

• Processes designed to measure and optimize the appropriate use of antimicrobials

• Achieved by selecting the appropriate agent, dose, duration of therapy and route of administration

• Implement systems to prompt clinicians to use appropriate agents – Annual antibiograms

• Implement process for review and feedback of prescribed antimicrobials

ALL MDROs

*Management of MDRO in Healthcare Settings, 2006 HICPAC

34 34

Most Common Reasons for Unnecessary Days of Therapy in Inpatients

576 (30%) of 1941 days of antimicrobial therapy deemed unnecessary

Hecker MT et al. Arch Intern Med. 2003;163:972-978.

ALL MDROs

Adapted from Spellberg B et al. Clin Infect Dis. 2004;38:1279-86.

New Antibacterial Agents Approved 1983-2011: The Pipeline is Dry

• Only 15-16 antibiotics are in development

• Only 8 of these have activity against key Gram neg bacteria

• None have activity against bacteria resistant to all current drugs

ALL MDROs

Antimicrobial Stewardship: A Spectrum of Activities

Comprehensive program led by ID

trained physician and pharmacist

Individual interventions based on goals of institution led by individual(s) with

interest

Many approaches in between

ALL MDROs

Examples of Stewardship Interventions • Formulary management

– Eliminate unnecessary duplication of agents – e.g. Pick one antibiotic in a class

• Pre-prescription review – Phone call placed or form filled out before pharmacy dispenses

antibiotic – e.g. Restrict expensive agents (e.g. daptomycin, linezolid)

• Post-prescription review – Downstream review of appropriateness of antibiotic therapy, usually

at 24-72 hours – e.g. Focus on use of an expensive drug (see above), commonly used

agent (vancomycin), on a disease state (bacteremia, asymptomatic bacteriuria), or on IV to PO conversion

ALL MDROs

Active Surveillance Testing • Practice of culturing asymptomatic patients

for the presence of MDRO (colonized) • Prevalence of MDRO may be greater than

anticipated, even if there have only been a few clinical cases

*Management of MDRO in Healthcare Settings, 2006 HICPAC

ALL MDROs

Practical Issues with AST and MDROs • Should you screen? • Which patient populations? • What screening test should you use? • Can you charge patients? • What sites should be cultured? • Do you isolate empirically? • Do you decolonize carriers? • What about screening healthcare workers?

ALL MDROs

Median 7 Control

Measures Employed per Study

MRSA

Huang SS et al Clin Infect Dis 2006;43:971+

MRSA

Harbarth S et al JAMA 2008;299:1149+

• Swiss study • Prospective cohort, with crossover design • 12 surgical wards • Rapid PCR detection of MRSA with contact

isolation, decontamination of patients if MRSA positive

• Outcomes: nosocomial invasive MRSA infections

MRSA

MRSA

Harbarth S et al JAMA 2008;299:1149+

• Low prevalence of MRSA in Switzerland • High hand hygiene compliance • Not randomized, single institution

• Observational study • 3 hospitals • Rapid PCR detection of MRSA • 3 phases: baseline, ICU screening,

universal screening

MRSA

Robicsek A et al Ann Intern Med 2008;148:409+

MRSA

Robicsek A et al Ann Intern Med 2008;148:409+

• Observational: no control arm • Changes in time to obtain study results • Single health system

Screening for MRSA? PROS

• Reduces transmission • Reduces MRSA infections (?) • Detects greater reservoir for transmission • Costs of program < costs of MRSA infections • Current practice is incomplete

– “Don’t Ask, Don’t Isolate”

MRSA

Screening for MRSA? CONS

• Other methods exist to prevent MRSA • What to do with screen + patients? • Marked logistics and costs

– Micro lab – Tech FTE, supplies – Isolation supplies – Negative impact of isolation – Upfront costs

MRSA

Harrington G et al ICHE 2007;28:837+

Decreasing MRSA without Active Surveillance Testing

• Interventions: – Antimicrobial hand

gel – Isolation signs – Feedback of data to

frontline

MRSA

Trends in Invasive MRSA Infections, U.S. 2005-2008

Kallen AJ. JAMA 2010;304:641-8

MRSA

Wenzel RP et al ICHE 2008;29:1012+

Interventions to Prevent Nosocomial MRSA: Prevent HAIs

MRSA

SHEA/IDSA Compendium (www.PreventingHAIs.com)

CDC’s Management of MDROs in Healthcare Settings, 2006. (www.cdc.gov/hicpac/mdro/mdro_0.html)

Hand hygiene Contact precautions

Cleaning and disinfection Education

Active surveillance testing Chlorhexidine bathing Decolonization therapy

Assess compliance with and impact of the

interventions

MRSA

Challenges with MDRO Control: A Regional Responsibility

Pts with KPC

Transmission within many

facilities

Won SY et al Clin Infect Dis 2011;53:532+

MDR GN

Conclusions

• MDROs are a problem of growing concern • There are an increasing number of strategies to

prevention MDRO transmission in healthcare settings

• Many gaps in knowledge re: best approach to MDRO control, adverse impact of control interventions; methods to overcome practical barriers to prevention efforts