Transcript Slide 1

Multidrug-resistant Organisms
in Health Care Settings
Sherman J. Alter, M.D.
Division of Infectious Disease
The Children’s Medical Center of Dayton
Department of Pediatrics
Boonshoft School of Medicine
Wright State University
Dayton, OH
Measles
H5N1
Monkeypox
NDM- beta lactamase
organisms
E. coli O104:H4
SARS
White nose
fungus
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
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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 drugresistant 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 pathogen
Risk 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.
2.
3.
4.
5.
MDRO and infection control risk assessment
MDRO and infection control performance assessment
Antibiotic stewardship
Transmission control
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 Infections
1. Vaccinate
2. Get the catheters out
Diagnose and treat infections
effectively
3. Target the pathogen
4. Access the experts
Use antimicrobials wisely
5. Practice antimicrobial control
6. Use local data
7. Treat infection, not
contamination
8. Treat infection, not colonization
9. Know when to say “no” to
“vanco”
10. Stop antimicrobial treatment
Prevent transmission
11. Isolate the pathogen
12. Break the chain of contagion
http://www.cdc.gov/drugresistance/healthcare/ha/12steps_HA.htm
Antimicrobial Resistance:
Key Prevention Strategies
Susceptible
Pathogen
Pathogen
Antimicrobial-Resistant
Pathogen
Prevent
Infection
Prevent
Transmission
Infection
Antimicrobial
Resistance
Effective
Diagnosis
& Treatment
Optimize Use
Antimicrobial Use
Mortality associated with carbapenem
resistant (CR) vs susceptible (CS)
Klebsiella pneumoniae (KP)
Percent of subjects
60
p<0.001
p<0.001
50
CRKP
40
CSKP
30
20
10
0
Overall Mortality
OR 3.71 (1.977.01)
Attributable
Mortality
OR 4.5 (2.16-9.35)
Patel G et al. ICHE 2008;29:1099-1106
Prevent Infection
Step 1: Vaccinate
Fact:
Pre-discharge influenza and pneumococcal vaccination
of at-risk hospital patients AND influenza vaccination
of healthcare personnel will prevent infections.
Kwong et al CLIN INFECT DIS 2009 49(5):750-756.
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.
Dayton Daily News 09/01/2011
CDC. MMWR. February 15, 2008 / 57(06);144-148
Prevent Infection
Step 2: Get the catheters out
Fact:
Catheters and other invasive devices are the # 1 exogenous
cause of hospital-onset infections.
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-related
bloodstream 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)
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Use maximal barrier precautions
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Remove catheter as soon as possible
Diagnose & Treat Infection Effectively
Step 3: Target the pathogen
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
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.
Use Antimicrobials Wisely
Step 5: Practice antimicrobial control
Fact: Programs to improve antimicrobial use are
effective – antibiotic stewardship
Associations between antimicrobial use and
the emergence of antimicrobial resistance
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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
% Imipenem-resistant
P. aeruginosa
Annual prevalence of imipenem resistance in
P. aeruginosa vs. carbapenem use rate
80
70
60
50
40
30
20
10
0
0
20
40
60
80
Carbapenem Use Rate
Gould et al. ICHE 2006;27:923-5
100
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 resistant
to macrolides (49% to 36%) Sabuncu et al. PLoS Med. 2009 June; 6(6): e1000084 (Epub)
Use Antimicrobials Wisely
Step 6: Use local data
Fact:
The prevalence of resistance can vary by time,
locale, patient population, hospital unit, and
length of stay.
0
Outpt
Inpt
Total
3rd Qtr 11
1st Qtr 11
3rd Qtr 10
1st Qtr 10
3rd Qtr 09
1st Qtr 09
3rd Qtr 08
1st Qtr 08
3rd Qtr 07
1st Qtr 07
3rd Qtr 06
1st Qtr 06
3rd Qtr 05
1st Qtr 05
3rd Qtr 04
1st Qtr 04
3rd Qtr 03
1st Qtr 03
Methicillin -resistant Staphylococcus aureus
DCMC
80
70
60
50
40
30
20
10
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-
Use Antimicrobials Wisely
Step 7: Treat infection,not contamination
Fact:
A major cause of antimicrobial overuse is
“treatment” of contaminated cultures.
Blood Culture Contamination Rate
5.0
% Contaminated
4.0
3.0
2.0
1.0
0.0
Mean blood culture contamination rate 1.9%. For ~600 children per quarter who had a
blood draw from the lab personnel, 12 had a contaminated blood culture.
DCMC Microbiology Laboratory
Blood Culture Contamination Rate
5.0
% Contaminated
4.0
3.0
Process change
implemented in
the ED
Training
implemented in
the lab
2.0
1.0
0.0
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
Use Antimicrobials Wisely
Step 9: Know when to say “no” to
vancomycin
Fact: Vancomycin overuse promotes emergence,
selection, and spread of resistant pathogens.
Evolution of Drug Resistance in S. aureus
Penicillin
S. aureus
Methicillin
Methicillin-resistant
Penicillin-resistant
[1950s]
S. aureus
[1970s]
S. aureus (MRSA)
Vancomycin
[1997]
[1990s]
Vancomycinresistant
S. aureus
[ 2002 ]
Vancomycin
intermediateresistant
S. aureus
(VISA)
Vancomycin-resistant
enterococci (VRE)
“Colonization pressure” in the spread of
vancomycin-resistant enterococcus
Bonten, M. J. M. et al. Arch Intern Med 1998;158:1127-1132.
Use Antimicrobials Wisely
Step 10: Stop antimicrobial treatment
Fact: Failure to stop unnecessary antimicrobial
treatment contributes to overuse and
resistance.
Actions:
when infection is cured
when cultures are negative and infection is
unlikely
when infection is not diagnosed
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 pathogen
Fact:
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 antimicrobialresistant pathogens from patient to patient.
Actions:
 stay home when you are sick
 contain your contagion
 keep your hands clean
 set an example!
The New York Times February 26, 2010
The β-lactam family of antibiotics
Penicillins
Benzylpenicillin
Methicillin
Cephalosporins Cephamycins Carbapenems
Cephalothin 1st
Cefamandole
2nd
Ampicillin
Cefuroxime 2nd
Carbenicillin
Cefotaxime 3rd
Mezlocillin
Ceftazidime 3rd
Ticarcillin
Ceftriaxone 3rd
Cefepime 4th
Cefoxitin
Imipenem
Meropenem
Cefotetan
Cefmetazole
Ertapenem
Doripenem
Monobactams
Aztreonam
The β-lactam family of antibiotics
Penicillins
Benzylpenicillin
Methicillin
Cephalosporins Cephamycins Carbapenems
Cephalothin 1st
Cefamandole
2nd
Cefoxitin
Imipenem
Meropenem
Cefotetan
Ertapenem
Ampicillin
Cefuroxime 2nd
Carbenicillin
Cefotaxime 3rd
Mezlocillin
Ceftazidime 3rd
Ticarcillin
Ceftriaxone 3rd
Cefepime 4th
Cefmetazole
Doripenem
ESBLs hydrolyze all
Penicillins
Cephalosporins
Monobactams
Monobactams
Aztreonam
The β-lactam family of antibiotics
Penicillins
Benzylpenicillin
Methicillin
Cephalosporins Cephamycins Carbapenems
Cephalothin 1st
Cefamandole
2nd
Ampicillin
Cefuroxime 2nd
Carbenicillin
Cefotaxime 3rd
Mezlocillin
Ceftazidime 3rd
Ticarcillin
Ceftriaxone 3rd
Cefepime 4th
Cefoxitin
Imipenem
Meropenem
Cefotetan
Cefmetazole
Ertapenem
Doripenem
ampCs hydrolyze all
Penicillins
Cephalosporins except
4th generation (cefepime)
Cephamycins
Monobactams
Monobactams
Aztreonam
The β-lactam family of antibiotics
Penicillins
Benzylpenicillin
Methicillin
Cephalosporins Cephamycins Carbapenems
Cephalothin 1st
Cefamandole
2nd
Ampicillin
Cefuroxime 2nd
Carbenicillin
Cefotaxime 3rd
Mezlocillin
Ceftazidime 3rd
Ticarcillin
Ceftriaxone 3rd
Cefepime 4th
Cefoxitin
Imipenem
Meropenem
Cefotetan
Cefmetazole
Ertapenem
Doripenem
Metallo BL hydrolyze all
Penicillins
Cephalosporins
Cephamycins
Carbapenems
Monobactams
Aztreonam
The β-lactam family of antibiotics
Penicillins
Benzylpenicillin
Methicillin
Cephalosporins Cephamycins Carbapenems
Cephalothin 1st
Cefamandole
2nd
Ampicillin
Cefuroxime 2nd
Carbenicillin
Cefotaxime 3rd
Mezlocillin
Ceftazidime 3rd
Ticarcillin
Ceftriaxone 3rd
Cefepime 4th
Cefoxitin
Imipenem
Meropenem
Cefotetan
Cefmetazole
Ertapenem
Doripenem
KPCs hydrolyze all
Penicillins
Cephalosporins
Cephamycins
Carbapenems
Monobactams
Monobactams
Aztreonam
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 Senso
Temple on April 28, 2007 in Tokyo, Japan. The first baby to cry wins the competition. The ceremony takes place
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