Multidrug-resistant Organisms in Health Care Settings
Sherman J. Alter, M.D.
Division of Infectious DiseaseThe Children’s Medical Center of
DaytonDepartment of Pediatrics
Boonshoft School of MedicineWright State University
Dayton, OH
NDM- beta lactamaseorganisms
White nosefungus
Monkeypox
E. coli O104:H4
SARSMeaslesH5N1
Impact of multidrug-resistant organisms (MDROs) on the health care system
• Infections caused by MDROs are associated with worsened clinical outcomes, including an increased risk of death.
• MDRO infections are also associated with significantly increased costs to hospitals, mostly attributable to increased length of stay.
• Media, legislative, and regulatory pressures are additional factors compelling hospitals to more effectively control MDROs.
Factors that might increase antimicrobial resistance in hospitals
• Greater severity of illness of hospitalized patients• More severely immunocompromised patients• Newer devices and procedures in use• Increased introduction of resistant organisms from the
community• Ineffective infection control and isolation practices and
compliance• Increased use of antimicrobial prophylaxis• Increased empiric polymicrobial antibiotic therapy• High antibiotic usage per geographic area per unit time
Clin Infect Dis 1997; 25:584-99
Risk factors for health care-associated infections and infection with drug-resistant
bacteria
Risk factors for health care-associated infections• Hospitalization for >2 days in preceding 90 days• Residence in nursing home or long-term care facility• Home infusion therapy, including antibiotics• Long-term dialysis within 30 days• Home wound care • Family member with multidrug-resistant pathogenRisk factors for infection with antibiotic-resistant bacteria• Antimicrobial therapy in preceding 90 days• Current hospitalization for >5 days• High frequency of antibiotic resistance in community or
specific hospital unit• Immunosuppression
Peleg et al. N Engl J Med 2010;362:1804-13
Rationale for MDRO control
Clinical consequences of MDROs Worsened patient morbidity/mortality
Economic consequences of MDROs ↑ costs of managing individual patients, opportunity costs, cost of control programs
Legislative mandates ↑ number of states require specific surveillance strategies; many promote or mandate public reporting.
Pay-for-performance measures Proposals to MRSA in CMS programs linked to ↓ hospital reimbursement
Public image and reputation Patient advocacy groups and media focused on MDRO preparedness
Medicolegal liability Lawsuits linking MRSA infection with hospital/provider neglect
From What Every Health Care Executive Should Know: The Cost of Antibiotic Resistance. Joint Commission Resources, 2009.
Elements of an effective multidrug resistant organism control program
1. MDRO and infection control risk assessment2. MDRO and infection control performance
assessment3. Antibiotic stewardship4. Transmission control5. Education
From What Every Health Care Executive Should Know: The Cost of Antibiotic Resistance. Joint Commission Resources, 2009.
Preventing antimicrobial resistance in health care settings
Prevent Infections1. Vaccinate2. Get the catheters outDiagnose and treat
infections effectively3. Target the pathogen4. Access the experts
Use antimicrobials wisely5. Practice antimicrobial control6. Use local data7. Treat infection, not
contamination8. Treat infection, not
colonization9. Know when to say “no” to
“vanco”10. Stop antimicrobial treatmentPrevent transmission11. Isolate the pathogen12. Break the chain of contagion
http://www.cdc.gov/drugresistance/healthcare/ha/12steps_HA.htm
Antimicrobial Resistance: Key Prevention Strategies
Optimize Use
PreventTransmission
PreventInfection
EffectiveDiagnosis& Treatment
PathogenAntimicrobial-Resistant Pathogen
Antimicrobial Resistance
Antimicrobial Use
Infection
Susceptible Pathogen
Mortality associated with carbapenem resistant (CR) vs
susceptible (CS) Klebsiella pneumoniae (KP)
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Patel G et al. ICHE 2008;29:1099-1106
OR 3.71 (1.97-7.01)
OR 4.5 (2.16-9.35)
Fact:Pre-discharge influenza and pneumococcal vaccination of at-risk hospital patients AND influenza vaccination of healthcare personnel will prevent infections.
Prevent Infection Step 1: Vaccinate
Respiratory antibiotic prescription rates over the study period, demonstrating year‐to‐year variability, temporal correlation with Ontario influenza viral surveillance data, and increasing influenza vaccination rates, with greater increases in Ontario than in other provinces combined. Respiratory antibiotic prescriptions are expressed as rate per 1000 people on the left vertical axis. Viral surveillance data (gray‐shaded areas) are expressed as the monthly percentage of positive test results on the right vertical axis. Vaccination rates for the household population aged 12 years (gray vertical bars, Ontario; ⩾black vertical bars, other provinces combined) are expressed as the percentage of the population vaccinated on the right vertical axis. The horizontal axis represents time. The black vertical line represents the introduction of the universal influenza immunization program (UIIP).
Kwong et al CLIN INFECT DIS 2009 49(5):750-756.
Dose‐response relationship between change in respiratory antibiotic prescriptions and influenza vaccination rate. The vertical axis represents the pre‐/post‐2000 relative rates for respiratory antibiotic prescriptions. The horizontal axis represents the absolute change in influenza vaccination rate for the household population aged 12 years from 1996–1997 to the mean during the post‐2000 period. Bubble ⩾size represents the inverse of the variance of the estimate of relative rate, used as the weighting factor in the weighted linear regression analysis. The solid line represents the weighted linear regression line, and the P value is for the regression coefficient. BC, British Columbia.
Kwong et al. CLIN INFECT DIS 2009 49(5):750-756.
Dayton Daily News 09/01/2011
CDC. MMWR. February 15, 2008 / 57(06);144-148
Fact: Catheters and other invasive devices are the # 1 exogenous cause of hospital-onset infections.
Prevent Infection Step 2: Get the catheters out
Biofilm on Intravenous Catheter Connecter 24 hours after Insertion
Scanning Electron Micrograph
Process of Catheter Related Infections
From the Quality and Safety Research Group Johns Hopkins University 2009
Risk Factors for catheter-relatedbloodstream infection
• Multiple lumen catheters-– increased tissue trauma predisposes to potential infection– more manipulation and contamination of multiple ports/hubs
• Total parenteral nutrition and/or lipid infusions
• Low nurse to patient ratio
• Site of insertion; subclavian vein poses less risk than internal jugular or femoral vein
Merrer et al. JAMA. 2001;286:700-7
Evidence based steps to preventing catheter-related bloodstream infections
• Clean hands (waterless alcohol based hand sanitizer or wash hands with soap and water)!
• Select best insertion site
• Use proper skin preparation (chlorhexidine)
• Use maximal barrier precautions
• Remove catheter as soon as possible
Fact:Appropriate antimicrobial therapy (correct regimen, timing, dosage, route, and duration) saves lives.
Diagnose & Treat Infection Effectively
Step 3: Target the pathogen
Fact: Appropriate antimicrobial therapy saves lives.
Actions: culture the patient target empiric therapy to likely pathogens
and local antibiogram target definitive therapy to known pathogens
and antimicrobial susceptibility test results
MDROs = microorganisms, predominantly bacteria, that are resistant to one or more classes of antibiotics. These pathogens are frequently resistant to most available antimicrobial agents
Diagnose & Treat Infection Effectively
Step 3: Target the pathogen
Organisms that can effectively “escape” the effects of antibacterial drugs
Enterobacter
Staphylococcus aureus
Klebsiella
Acinetobacter
Pseudomonas aeruginosa
Enterococcus
IDSA. Clin Infect Dis 2009;48 (1 January)
Causative agents with 3-class and 4-class antimicrobial resistance within infection types
(National Healthcare Safety Network, 2006-2007)
Kallen et al. Infect Control Hosp Epidemiol 2010;31:528–531
Giske et al. Antimicrobial Agents and Chemotherapy 2008; 52(3): 813-21.
Fact: Programs to improve antimicrobial use are effective – antibiotic stewardship
Use Antimicrobials Wisely Step 5: Practice antimicrobial control
Associations between antimicrobial use and the emergence of antimicrobial resistance
• Changes in antimicrobial use are paralleled by changes in the prevalence of resistance.
• Antimicrobial resistance is more prevalent in healthcare-associated bacterial infections, compared with those acquired in the community.
• Patients with healthcare-associated infections caused by resistant strains are more likely than control patients to have received prior antibiotics.
• Areas within hospitals that have the highest rates of antimicrobial resistance also have the highest rates of antimicrobial use.
• Increasing duration of patient exposure to antimicrobials increases the likelihood of colonization with resistant organisms.
IDSA and SHEA Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship Clin Infect Dis 2007; 44:159-77
Annual prevalence of imipenem resistance in P. aeruginosa vs. carbapenem use rate
0 10 20 30 40 50 60 70 80 900
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Carbapenem Use Rate
% I
mip
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. aeru
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Gould et al. ICHE 2006;27:923-5
Mechanisms for the appearance or spread of antimicrobial resistance in
hospital organisms• Introduction of a resistant organism to a
susceptible population• Acquisition of resistance by a susceptible strain
– Spontaneous mutation– Genetic transfer
• Expression of a regulated resistance already present in the population
• Selection of a resistant subpopulation• Dissemination or spread of resistant organisms
Clin Infect Dis 1997; 25:584-99
32
Infectious Disease Society of America (IDSA) Society for Healthcare Epidemiology of
America (SHEA)CID 2007:44 159-177
Antibiotic stewardship: methods to control antimicrobial use to prevent or control antimicrobial resistance
• Optimal use of all antimicrobials (e.g., incorporate practice guidelines)
• Selective removal, control, or restriction of antimicrobial agents or classes
• Rotational or cyclic antimicrobial utilization• Use of combination antimicrobial therapy to prevent the
emergence of resistance• Formulary restriction • Intravenous to oral switch• Automatic stop orders• Computerized order entry• Provider education (best when used • with other interventions)
Ten Strategies proposed by IDSA and SHEA for implementation of an Antibiotic
Stewardship (AS) Program
1. Prospective audit with intervention and feedback (A-I)
2. Formulary restriction and pre-authorization (A-II)3. Education with intervention (A-III)4. Guidelines with clinical pathways (A-III)5. Antimicrobial cycling (C-II)6. Antimicrobial order forms (B-II)7. Reducing combination therapy (C-II)8. Streamlining and de-escalation therapy (A-II)9. Dose optimization (A-II)10. Parenteral or oral conversion (A-III)
Carbapenem-resistant Pseudomonas aeruginosa and carbapenem utilization
Lepper et al. AAC 2002;46:2920-5
Winter antibiotic prescriptions, France by region, October 2000 to March 2007
From 2001 to 2006, a decreasing trend was observed in the rate of pneumococci resistant to penicillin (47% to 32% of isolates) and the rate of pneumococci resistantto macrolides (49% to 36%) Sabuncu et al. PLoS Med. 2009 June; 6(6): e1000084 (Epub)
Fact: The prevalence of resistance can vary by time, locale, patient population, hospital unit, and length of stay.
Use Antimicrobials Wisely Step 6: Use local data
Methicillin -resistant Staphylococcus aureusDCMC
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Surveillance as a strategy to prevent the spread of MDROs
Active surveillance to identify patients colonized but not overtly infected with MDROs– Specimens from body sites can be submitted
for culture– By identifying these individuals, measures can
be taken to prevent the spread to other patients.
– Active surveillance has been shown to reduce the frequency of MDRO infection in specific populations in a wide variety of settings.
CDC. MMWR 2009;58:256-258
Fact: A major cause of antimicrobial overuse is “treatment” of contaminated cultures.
Use Antimicrobials WiselyStep 7: Treat infection,not contamination
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DCMC Microbiology Laboratory
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Process change implemented in the ED
Training im-plemented in the lab
Mean blood culture contamination rate decreased from 3.3% to 1.4% 2001-2009. The number of children with a contaminated blood culture was reduced from 236 to 103 (7130 blood cultures per year total). That’s 133 children spared repeat visits, admissions, prolonged stays, excess charges and potential hospital acquired infections by undergoing further evaluations or being admitted unnecessarily.
DCMC Microbiology Laboratory
Fact: Vancomycin overuse promotes emergence, selection, and spread of resistant pathogens.
Use Antimicrobials WiselyStep 9: Know when to say “no” to vancomycin
S. aureus
Penicillin
[1950s]Penicillin-resistant
S. aureus
Evolution of Drug Resistance in S. aureusMethicillin
[1970s]
Methicillin-resistant
S. aureus (MRSA)
Vancomycin-resistantenterococci (VRE)
Vancomycin
[1990s]
[1997]
Vancomycinintermediate-
resistantS. aureus (VISA)
[ 2002 ]Vancomycin-
resistantS. aureus
Bonten, M. J. M. et al. Arch Intern Med 1998;158:1127-1132.
“Colonization pressure” in the spread of vancomycin-resistant enterococcus
Fact: Failure to stop unnecessary antimicrobial treatment contributes to overuse and resistance.
Actions:when infection is curedwhen cultures are negative and
infection is unlikelywhen infection is not diagnosed
Use Antimicrobials Wisely Step 10: Stop antimicrobial
treatment
Effect of antibiotic prescribing in primary care on
antimicrobial resistance in individual patients:
systematic review and meta-analysis
Costelloe C et al. BMJ.
2010;340:c2096.
Prevent Transmission Step 11: Isolate the
pathogenFact: Patient-to-patient spread of pathogens can
be prevented.
Actions:use standard infection control precautions contain infectious body fluids
(use approved airborne/droplet/contact isolation precautions)
when in doubt, consult infection control experts
Isolation precautions to prevent the spread of MDROs
• The use of gowns and gloves when in a patient room is the standard of care for preventing transmission from patients with MDROs– Compliance is always an ongoing
challenge!– Personal protective equipment (PPE)
utilized prior to entering the room and removed prior to leaving the room.
– Special contact isolation with MDROs
http://www.who.int/gpsc/country_work/hhsa_framework.pdf
Environmental hygiene to minimize the spread of MDROs
• Targeted to eliminate the reservoir of MDROs on hospital surfaces and equipment– MDROs can persist in the environment
despite routine cleaning practices– Some resistant organisms can remain for
weeks without proper surface disinfection– Patients admitted to rooms previously
occupied by a patient with an MDRO are at higher risk for developing infection with that organism.
Decolonization to prevent the spread of MDROs
• Aims to eradicate resistant bacteria from colonized patients in an effort to prevent subsequent infection or spread– Topical antibiotics are often utilized– Limited experience in the use of
decolonization in general hospital patients– Current guidelines, citing concern for the
development of resistance to the drugs used for decolonization, advise against widespread use of this practice
Prevent Transmission Step 12: Break the chain of
contagion
Fact: Healthcare personnel can spread antimicrobial-resistant pathogens from patient to patient.
Actions:stay home when you are sick contain your contagionkeep your hands cleanset an example!
The New York Times February 26, 2010
The β-lactam family of antibiotics
Ceftriaxone 3rdTicarcillin
Ceftazidime 3rdMezlocillin
Cefotaxime 3rdCarbenicillin
Ertapenem
CefmetazoleCefuroxime 2ndAmpicillin
MeropenemCefotetanCefamandole 2ndMethicillin
AztreonamImipenemCefoxitinCephalothin 1stBenzyl-penicillin
MonobactamsCarbapenemsCephamycinsCephalosporinsPenicillins
Cefepime 4th
Doripenem
The β-lactam family of antibiotics
Ceftriaxone 3rdTicarcillin
Ceftazidime 3rdMezlocillin
Cefotaxime 3rdCarbenicillin
Ertapenem
CefmetazoleCefuroxime 2ndAmpicillin
MeropenemCefotetanCefamandole 2ndMethicillin
AztreonamImipenemCefoxitinCephalothin 1stBenzyl-penicillin
MonobactamsCarbapenemsCephamycinsCephalosporinsPenicillins
Cefepime 4th
ESBLs hydrolyze all PenicillinsCephalosporinsMonobactams
Doripenem
The β-lactam family of antibiotics
Ceftriaxone 3rdTicarcillin
Ceftazidime 3rdMezlocillin
Cefotaxime 3rdCarbenicillin
Ertapenem
CefmetazoleCefuroxime 2ndAmpicillin
MeropenemCefotetanCefamandole 2ndMethicillin
AztreonamImipenemCefoxitinCephalothin 1stBenzyl-penicillin
MonobactamsCarbapenemsCephamycinsCephalosporinsPenicillins
Cefepime 4th
ampCs hydrolyze all PenicillinsCephalosporins except4th generation (cefepime)CephamycinsMonobactams
Doripenem
The β-lactam family of antibiotics
Ceftriaxone 3rdTicarcillin
Ceftazidime 3rdMezlocillin
Cefotaxime 3rdCarbenicillin
Ertapenem
CefmetazoleCefuroxime 2ndAmpicillin
MeropenemCefotetanCefamandole 2ndMethicillin
AztreonamImipenemCefoxitinCephalothin 1stBenzyl-penicillin
MonobactamsCarbapenemsCephamycinsCephalosporinsPenicillins
Cefepime 4th
Metallo BL hydrolyze all PenicillinsCephalosporins CephamycinsCarbapenems
Doripenem
The β-lactam family of antibiotics
Ceftriaxone 3rdTicarcillin
Ceftazidime 3rdMezlocillin
Cefotaxime 3rdCarbenicillin
Ertapenem
CefmetazoleCefuroxime 2ndAmpicillin
MeropenemCefotetanCefamandole 2ndMethicillin
AztreonamImipenemCefoxitinCephalothin 1stBenzyl-penicillin
MonobactamsCarbapenemsCephamycinsCephalosporinsPenicillins
Cefepime 4th
KPCs hydrolyze all PenicillinsCephalosporins CephamycinsCarbapenemsMonobactams
Doripenem
CMAJ October 2010
Conclusions: Key Prevention Strategies
Prevent infection Diagnose and treat infection
effectively
Use antimicrobials wisely
Prevent transmission
Education
“Mankind faces a crossroads. One path leads to despair and utter hopelessness, the other to total extinction.”
Woody Allen
Sumo wrestling students hold babies as they try to make them cry during the Crying Sumo competition at Sensoji Temple on April 28, 2007 in Tokyo, Japan. The first baby to cry wins the competition. The ceremony takes place in Japan to wish for the good health of the child as it is said that crying is good for the health of babies.
April 29, 2007 - Photo by Junko Kimura/Getty Images News
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