practical aspects of control of multidrug resistant ......practical aspects of control of multidrug...
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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
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