1) A study investigated an outbreak of infections caused by a multidrug-resistant Klebsiella pneumoniae strain in an ICU between November and December 2000. 2) The outbreak was associated with contaminated roll boards used in operating rooms. 3) Active surveillance cultures identified 4 patients infected and 1 colonized with the outbreak strain within 2-18 days of surgery.

1. Multidrug Resistant Organisms
Danae Bixler, MD, MPH

2. Objectives
• Definitions
• Explain:
– Which MDROs are important and why
– Reservoir for MDROs
– Resistance to key antibiotics
– Surveillance
– Control measures
– Challenges of outbreak investigation
2

3. Public Health Significance of Multi-
Drug Resistance
http://www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf
• Increased:
– Cost
– Length of stay
– Admissions to ICU
– Surgical procedures
– Morbidity
– Mortality
3

4. EXAMPLE – CONTROL OF A
VANCOMYCIN-RESISTANT
ENTEROCOCCUS IN HEALTH CARE
FACILITIES IN A REGION
N Engl J Med, 2001; 344:1427-1433
4

5. Siouxland region of Iowa, Nebraska
and South Dakota
N Engl J Med, 2001; 344:1427-1433
• 4 acute care facilities
• 28 long term care facilities
• Population 135,000
• December 1996 - April 1997 - isolates of VRE
increased from 0 to 63
• Meeting of health care facilities, District
Health Department, state health departments,
Indian Health Service
5

6. Plan: Active Surveillance
N Engl J Med, 2001; 344:1427-1433
Acute Care Facilities
• Patients transferred from
acute care facilities outside
the community
• Patients:
– hospitalized longer than 72
hours;
– on dialysis, with cancer,
transplant or in ICU;
– who have had prolonged
treatment with antimicrobial
agents; or
– with invasive devices
Long Term Care Facilities
• Patients admitted from acute
care with unknown VRE status
(pre-emptive contact
precautions)
• Patients:
– hospitalized longer than 72
hours;
– on dialysis, with cancer,
transplant or in ICU;
– who have had prolonged
treatment with antimicrobial
agents; or
– with invasive devices
6

7. Plan: Infection Control
N Engl J Med, 2001; 344:1427-1433
Isolation and
Infection
Control
Precautions
Acute Care Facility Long Term Care Facility
Room
assignment
Private or cohort Private > cohort > place with non-
colonized roommate IF:
•Roommate has NO immunosuppression
or broken skin or renal failure AND
•Both roommates able to wash hands AND
•VRE patient DOES NOT HAVE urinary or
fecal incontinence or draining wound
7

8. Plan: Infection Control
N Engl J Med, 2001; 344:1427-1433
Isolation and Infection
Control Precautions
Acute Care Facility AND Long Term Care Facility
VRE status System of identifying the records of patients with
infection or colonization
Barrier precautions Gloves for direct patient contact; gowns for
substantial contact with patient or body fluids
Hand washing Health care workers, patients, and visitors
Care of equipment Dedicated non-critical equipment / cleaning or
disinfecting with approved disinfectants
Education Healthcare workers, patients, visitors
Communication VRE status indicated on transfer sheets and orally
8

9. Colonization Rates, 1997 – 1999,
Siouxland Region
N Engl J Med, 2001; 344:1427-1433
Type of
Facility
Colonization with VRE
Number of Patients (%)
1999 versus 1997
1997 1998 1999 Relative Risk (95% CI) P value
All 40 (2.2) 26 (1.4) 9 (0.5) 0.2 (0.01 – 0.05) < 0.001
Acute care 10 (6.6) 9 (5.5) 0 0 < 0.001
Long term
care
30 (1.7) 17 (1.0) 9 (0.5) 0.3 (0.2 – 0.7) 0.001
9

10. Prevention Collaborative
http://www.cdc.gov/hai/recoveryact/stateResources/collaborationPrimer.html
• Coordinator
• Multidisciplinary advisory group
• Healthcare facility participation
– Written commitment / Letters of support
• Prevention strategies
– Science-based
– Feasible
10

11. Prevention Collaborative
http://www.cdc.gov/hai/recoveryact/stateResources/collaborationPrimer.html
• Meetings
– Agree on goals
– Share learning, communication and feedback
• Measurement
– Select a measurement system (e.g., NHSN)
– Facility commitment to participate
– Regular feedback
• Ongoing communication
11

12. MDROs Reported to NHSN, 2006-2007
Infect Control Hosp Epidemiol, 2008; 29:996-1011
Organism Resistant to Number of
isolates tested
Resistance
percentage
Staphylococcus
aureus
Oxacillin 2736 56.2
Enterococcus
faecium
Vancomycin 969 80.0
Enterococcus
faecalis
Vancomycin 1,497 6.9
Pseudomonas
aeruginosa
Fluoroquinolones 2,185 30.7
Piperacillin or
piperacillin/tazobactam
1545 17.5
Amikacin 1,444 6.0
Imipenem or miropenem 1,558 25.3
Cefepime 1,604 11.2
12

13. MDROs Reported to NHSN, 2006-2007
Infect Control Hosp Epidemiol, 2008; 29:996-1011
Organism Resistant to Number of
isolates tested
Resistance
percentage
Klebsiella
pneumoniae
Ceftriaxone or ceftazidime 329 - 579 21.2 – 27.1
Imipenem, meropemen or
ertapenem
302 - 452 3.6 – 10.8
Klebsiella oxytoca Ceftriaxone or ceftazidime 232 16.8
Imipenem, meropemen or
ertapenem
181 2.8
Acinetobacter
baumannii
Imipenem or meropemen 82 - 427 25.6 – 36.8
Escherichia coli Ceftriaxone or ceftazidime 173 – 1,577 5.5 – 11.0
Imipenem, meropemen or
ertapenem
163 - 871 0.9 – 4.0
Fluoroquinolones 255 – 1,920 22.7 – 30.8
13

14. Reservoirs for MDROs
Organism Reservoir Colonizes In hospital environment
Staphylococcus
aureus
Nares, skin Nares, skin Stethoscopes, pagers, bed spaces,
linens, wheelchairs, doorknobs,
workstations, telephones …
Enterococcus
species
Intestines Intestines Bed rails, linens, doorknobs,
bedpans, urinals, blood pressure
cuffs, stethoscopes, monitoring
equipment
Pseudomonas
aeruginosa
Soil, water,
plants
Axilla, ear,
perineum,
respiratory tract
Drains, toilets, showers, water in
patient equipment
Acinetobacter
species
Soil, water,
food
Pharynx,
especially
tracheostomy
Tap water, peritoneal dialysate
bath, urinals, washcloths, soap
dispensers
Enterobacteriaceae
(Klebsiella,
Enterobacter, E.Coli)
Intestines Oropharynx,
genitourinary
tract
Sinks, ultrasonography gel, bath
soap, water baths
14

15. Resistance 101
Staphylococcus aureus
Antibiotic Resistance
mechanism
Label Alternate antibiotics
Penicillin β – lactamase
(inducible plasmid)
Nafcillin, oxacillin,
methicillin
Methicillin
(penicillinase-stable
β-lactam antibiotic)
Staphylococcal
chromosomal
casette (SCC) mec
•6 types
•Associated with
resistance to other
antibiotics
•MRSA •Vancomycin
Glycopeptides •Chromosomal
mutation
•VRSA
•VISA
•?
15

16. Resistance 101
Enterococcus
Antibiotic Resistance
mechanism
Label Alternate
antibiotics
Ampicillin Decreased binding
of antibiotic
(chromosomal)
Ampicillin resistant Ampicillin and
aminoglycoside
Aminoglycosides Aminoglycoside-
modifying enzyme
(chromosomal)
High-level
(aminoglycoside)
resistant (HLR)
Vancomycin
Vancomycin Reduced binding of
drug to cell wall
(plasmid)
VRE •?
16

17. Resistance 101
Gram Negative Bacilli
Antibiotic Resistance
mechanism
Label Alternate
antibiotics
Penicillins, 1st
, 2nd
and 3rd
generation
cephalosporins and
aztreonam
Extended-spectrum
β – lactamases
Chromosomal or
plasmid
•Also frequently
resistant to:
fluoroquinolones,
co-trimoxazole,
trimethoprim
ESBL-producing - Carbapenems
Carbapenems Carbapenemase
•Transposon
(mobile genetic
material)
CRE (Carbapenem
resistant
enterobacteriaceae)
•? / Colistin and
Polymyxin B
17

18. Types of Infections Caused by MDROs
Gram (+) Cocci
Mandell, 7th
Edition
Bacteria Types of infections
Staphylococcus aureus •Surgical site infections (SSI)
•Central line-associated bloodstream
infections (CLABSI)
•Ventilator-associated pneumonias
(VAP)
•Bacteremia
•Osetomyelitis, septic arthritis
•Other organs …
18

19. Types of Infections Caused by MDROs
Gram (+) Cocci (2)
Mandell, 7th
Edition
Bacteria Types of infections
Enterococcus species •Bacteremia
•Catheter-associated urinary tract
infections (CAUTI)
•Intra-abdominal and pelvic infections
•Neonatal infections
•Skin and soft tissue
19

20. Types of Infections Caused by MDROs
Gram (-) Bacilli
Mandell, 7th
Edition
Bacteria Types of infections
Pseudomonas aeruginosa •Bacteremia
•Acute pneumonia, chronic respiratory infections
•Bone and joint
•Ear, eye
•UTI
•Skin and soft tissue (e.g., burns)
Acinetobacter species •Pneumonia
•Bacteremia
•Cellulitis after surgery or trauma
Enterobacteriaceae
Klebsiella species
Enterobacter sp
E.coli
•UTI
•Neonatal bacteremia
•Sepsis and meningitis
•Pneumonia
•Wound and burn infections
•CLABSIs
20

21. Surveillance
http://www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf
• Routine clinical cultures (antibiograms)
– Detect emergence of new MDROs
– Facility- or unit- specific summary antimicrobial
susceptibility reports
• Monitor for changes
• MDRO incidence (new isolates per 1000
patient days or per month)
– Monitor trends / evaluate impact of prevention
– Does not distinguish colonization from infection
21

22. Surveillance
http://www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf
• MDRO infection rates
– Requires clinical data
– Helpful in defining clinical impact
• Molecular typing
– Confirm clonal transmission
– Evaluate interventions in facility
22

23. Active Surveillance Cultures
http://www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf
• Prospective identification of colonized persons
• Coupled with intervention can reduce
transmission
• Resource intensive
• Methods
– MRSA: nares > perirectal and wound
– VRE: stool, rectal or perirectal
– MDR-GNB: peri-rectal or rectal alone or in
combination with oropharyngeal, endotracheal,
inguinal, or wound
23

24. EXAMPLE – UNIVERSAL SURVEILLANCE
FOR MRSA IN 3 AFFILIATED HOSPITALS
Ann Intern Med, 2008; 148:409-418.
24

25. Infection Control Strategies
Evanston Northwestern Healthcare
Ann Intern Med, 2008; 148:409-418
• 3 hospitals
– 40,000 annual admissions
– 450 staff physicians
• Contact isolation for MRSA-colonized persons
– Private room or cohort
– Gowns and gloves for all room entries
– Dedicated equipment, e.g., stethoscopes
25

26. Study Design
Ann Intern Med, 2008; 148:409-418
Timeframe Period 1 (Aug 1,
2003 – July 31,
2004)
Period 2 (Aug 1,
2004 – July 31,
2005)
Period 3 (Aug 1,
2005 – April 2007)
Strategy No active
surveillance
ASC at ICU
admission
ASC at any
admission
Admissions tested
(%)
0 (0%) 3334 (75.9%) 62,035 (84.4%)
Positive test results 0 277 (8.3%) 3926 (84.4%)
Contact precautions
for MRSA
yes yes yes
Routine
decolonization
no no Mupirocin,
chlorhexidine
MRSA per 10,000
patient-days
(95% CI)
8.9
(7.6 – 10.4)
7.4
(6.1 – 9.0)
3.9
(3.2 – 4.7)
26

27. Ann Intern Med, 2008; 148:409-418
27

28. Infection Control Precautions
http://www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf
• Standard precautions
– Masks for:
• Splash-generating procedures
• Patients with open tracheostomies
• Circumstances when there is evidence of transmission from heavily colonized
sources (e.g., burns)
• Contact precautions
– All patients with infections or previously identified as colonized
– Patients with ability to perform hand hygiene and without draining
wounds, diarrhea, uncontrolled secretions: establish ranges of
permitted ambulation, socialization and use of common areas based
on risk …
• Cohorting, in order of preference:
– Single patient room
– Cohort with patient with same MDRO
– Cohort with low-risk patient
28

29. Infection Control Precautions
http://www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf
• Environmental measures
– Increased cleaning of:
• Items in close proximity to patient, e.g., bed rails, over-
bed tables
• Frequently touched surfaces
– Monitoring
• Decolonization
29

30. EXAMPLE – OUTBREAK OF INFECTION
WITH A MULTIRESISTANT KLEBSIELLA
PNEUMONIAE STRAIN ASSOCIATED
WITH CONTAMINATED ROLL BOARDS
IN OPERATING ROOMS
J Clin Microbiol, 2005; 43:4961-4967.
30

31. Case definition
J Clin Microbiol, 2005; 43:4961-4967.
• “Cases were defined as patients who were
admitted to the ICU for > 24 h in November
2000 and who were positive for MRKP* by
culture of specimens taken between 1
November 2000 and 31 December 2000.
• Samples for culture were taken from specific
infection sites or for surveillance, and samples
from both colonized and infected patient
were included.”
*resistant to trimethoprim-sulfamethoxazole and aminoglycosides; ESBL
positive
31

32. Description of Cases
J Clin Microbiol, 2005; 43:4961-4967.
Case Reason for
Admission
Date Date of
first culture
First positive
specimen
Days
between
surgery and
collection
1 Laparotomy 10/26 11/2 Abdominal wounds 4
2 Subdural empyema 11/4 11/6 Sputum 2
3 Trauma 11/8 11/11 Blood 2
4 Pancreatitis 10/30 11/18 Discharge from ear 1
5 Esophageal
resection
10/18 11/18 Discharge from
thorax drain
5
6 Laparotomy 11/7 11/23 Sputum 15
7 Subarachnoid
hemorrhage
11/24 12/19 CSF none
32

33. Genotyping of Isolates from Patients
and OR Rollboards
J Clin Microbiol, 2005; 43:4961-4967.
33

34. Disinfectants for non-critical items
Practical Healthcare Epidemiology, 3rd
Edition;
http://www.cdc.gov/hicpac/pdf/guidelines/Disinfection_Nov_2008.pdf
• Chlorine-based products
– Sporicidal
– Corrosive
– Respiratory irritant
– Inactivation by organic matter
• Phenolics
– Bactericidal, fungicidal, virucidal, tuberculocidal
– Tissue irritant
– Hyperbilirubinemia in neonatal nursery
34

35. Disinfectants for non-critical items
Practical Healthcare Epidemiology, 3rd
Edition;
http://www.cdc.gov/hicpac/pdf/guidelines/Disinfection_Nov_2008.pdf
• H2O2
– Bactericidal, fungicidal, virucidal, sporicidal
– Chemical irritant
• Quaternary ammonium compounds
– Bactericidal, fungicidal, virucidal against lipophilic (enveloped)
viruses
– Not sporicidal, tuberculocidal or active against hydrophilic
viruses.
– Inactivated by water hardness and cotton
• 70-90% alcohol
– Virucidal, tuberculocidal
– Lack sporicidal action and cannot penetrate
protein-rich materials
– Damage some surfaces after repeated use
35

36. EXAMPLE – NOSOCOMIAL OUTBREAK
OF INFECTION WITH PAN-DRUG-
RESISTANT ACINETOBACTER
BAUMANNII IN A TERTIARY CARE
UNIVERSITY HOSPITAL
Infect Control Hosp Epidemiol, 2009; 30:257-263.
36

37. Case Definition
Infect Control Hosp Epidemiol, 2009; 30:257-263.
• “A case patient was defined as any inpatient
who had a pan-drug-resistant A baumannii
isolate recovered from a clinical or
surveillance sample obtained at least 48 hours
after ICU admission {from April 9, 2002 to
March 9, 2003}.”
37

38. Infect Control Hosp Epidemiol, 2009; 30:257-263.
38

39. Interventions to Control Pan-Drug-
Resistant Acinetobacter baumannii
Infect Control Hosp Epidemiol, 2009; 30:257-263.
• Environmental decontamination
• Environmental survey
• Revision of cleaning protocols
• Active surveillance for PDRAB
– Rectal and pharyngeal swabs of roommates
• Educational programs for the staff
• Display of posters illustrating isolation measures
and antimicrobial use recommendations
39

40. Intensified MDRO Control Measures
http://www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf
• Obtain consultation
• Evaluate staffing and resources
• Educate
• Judicious antimicrobial use
• Active surveillance and pre-emptive contact
isolation
• Contact precautions for all colonized or
infected patients
40

41. Intensified MDRO Control Measures
http://www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf
• Stop new admissions to the unit or facility if
transmission continues
• Dedicated use of non-critical equipment
• Training for environmental staff
• Monitor cleaning
• Vacate units for intensive cleaning when previous
efforts fail
• Decolonization for MRSA (only) with expert
consultation
41

42. EXAMPLE – SUCCESSFUL CONTROL OF
AN OUTBREAK OF CARBAPENEMASE-
PRODUCING KLEBSIELLA PNEUMONIAE
IN A LONG TERM ACUTE CARE
HOSPITAL
Infect Control Hosp Epidemiol, 2010; 31: 341-347.
42

43. Infect Control Hosp Epidemiol, 2010; 31: 341-347.
43

44. Bundled Intervention
Infect Control Hosp Epidemiol, 2010; 31: 341-347
• Daily chlorhexidine baths for all patients
– 2% chlorhexidine from the jawline downward
• Observational study of terminal cleaning
– Bedrails, IV pumps, poles, respiratory tubing, etc. not
cleaned at all
• Environmental cleaning
– Cleaning personnel - clean all surfaces
– Respiratory therapy - nightly cleaning of all
mechanical ventilator surfaces and O2 valves
– Nursing – disinfect all shared objects
– All bedside curtains replaced
44

45. Bundled Intervention
Infect Control Hosp Epidemiol, 2010; 31: 341-347
• Surveillance cultures on new admissions
• Surveillance rectal swabs on all patients
• Isolation and contact precautions
– High risk patients placed in pre-emptive contact
isolation (CI) on admission until documented (-)
– (+) patients placed in CI
• Personnel education
• Environmental cultures to monitor cleaning
45

46. Infect Control Hosp Epidemiol, 2010; 31: 341-347.
46

47. EXAMPLE – MANAGEMENT OF A
MULTIDRUG-RESISTANT
ACINETOBACTER BAUMANNII
OUTBREAK IN AN INTENSIVE CARE UNIT
USING NOVEL ENVIRONMENTAL
DISINFECTION: A 38 MONTH REPORT
Am J Infect Control, 2010; 38: 259.
47

48. Case Definition
Am J Infect Control, 2010; 38: 259
• Identification of A baumannii recovered from
a patient with an apparent clinical infection
due to this pathogen after more than 2 days in
the ICU.
48

49. Infection Control Bundle
Am J Infect Control, 2010; 38: 259
• Addition of a new hand hygiene product –
alcohol-based hand gel in each patient room
• Hand hygiene training
• Observations of environmental cleaning
• Contact isolation of all MDR A baumannii
patients
• Environmental culturing
– A baumannii isolated from drain
49

50. Am J Infect Control, 2010; 38: 259
50

51. Conclusions
• MDROs can be controlled
– Surveillance
– Standard precautions (handwashing)
– Contact precautions
– Environmental cleaning
– Monitoring of above
– Interfacility collaboration and communication
51

52. Strategies to Prevent Transmission of Methicillin-
Resistant Staphylococcus aureus in Acute Care
Hospitals
Infect Control Hosp Epidemiol, 2008; 29(Suppl 1): S62
• MRSA risk assessment
• MRSA monitoring program
• Hand hygiene guidelines
• Contact precautions for MRSA-infected or colonized
patients
• Cleaning and disinfection of equipment and the
enivronment
• Educate
• Laboratory alert system
• Provide MRSA data and outcome measures to key
stakeholders
• Educate patients and families
52