Multidrug-resistant Organisms in Health Care Settings

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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osa

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





Ertapenem





Cefepime 4th

ESBLs hydrolyze all PenicillinsCephalosporinsMonobactams

Doripenem





Ertapenem





Cefepime 4th

ampCs hydrolyze all PenicillinsCephalosporins except4th generation (cefepime)CephamycinsMonobactams

Doripenem





Ertapenem





Cefepime 4th

Metallo BL hydrolyze all PenicillinsCephalosporins CephamycinsCarbapenems

Doripenem





Ertapenem





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

Multidrug-resistant Organisms in Health Care Settings

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