Controlling Nosocomial MRSA and VRE Infections By Using Active Surveillance Cultures and Contact Pre

1
Controlling Nosocomial MRSA and VRE Infections By
Using Active Surveillance Cultures and Contact
Precautions
The Problem Pathogen Partnership
2
Source Global Health Situations
Projections, Estimates 1992, World Health
Organization, Geneva, Switzerland, 1992.
3
Antibiotic Resistant Infections

• Importance
• Prolonged illness
• Prolonged hospital stay
• Higher mortality
• Greater excess costs
• Greater potential for still worse infections
  like VRSA by not controlling spread of MRSA and
  VRE

For more info and slides on this topic
www.pppsite.org
4
Rapid Increase in the Prevalence of
Penicillin-resistant Staphylococcus aureus,
Hammersmith Hospital, London
1941 lt1 1946 13 1947 38 1948 59
5
Mechanisms Of Developing Antibiotic Resistance

• Random genetic mutation.
• Plasmid swapping during conjugation.
• Movement of transposons to plasmids/chromosomes.
• Transduction by bacteriophages.
• Transformation (acquisition of resistant genes
  from a recently killed cell and incorporation
  into a chromosome or plasmid).
• Binary fission (replication) can share any of
  the above.

6
Mechanisms Of Developing Antibiotic Resistance
Natural Selection
Darwin C. On the Origin of Species by Means of
Natural Selection, London, 1859.
7
Prevalence of Antibiotic Therapy in U.S.
Hospitals In Recent Surveys

• Almost half of all patients
• Almost all ICU patients

8
Univariate Analysis Of Antibiotic Exposure
9
VRE Incidence
WeekHospital Ward 1 2 3
4 6th Floor ICU 0 0 0 0
Step-down Unit 0 0 0 0 5th
Floor ICU 2 1 0 0
Step-down Unit 4 2 1 1 3rd
Floor ICU 1 1 1 0
Step-down Unit 6 3 0 1
Byers KE, et al. ICHE 200122(3)140-147.
10

Byers KE, et al. ICHE 200122(3)140-147.
11
Transmission Of IndividualClones Of VRE
Boyce, J Cin Micro 1994321148.Dembry, SHEA
1994 Abstract 28.Edmond, Clin Infect Dis
1995201126.Handwerger, Clin Infect Dis
199316750.Livornese, Ann Int Med
1992117112.Montecalvo, Anti Ag Chemo
1994381363.Rubin, Infect Cont Hosp Epi
199213700.
12
Yin
Yang
13
Possible Control Measures

• Antibiotic control
• Prevention of spread
• a) hand hygiene for all patient
  contacts (Universal/Standard Precautions)
• b) identify colonized patients with
  active surveillance cultures and use
  barrier precautions to prevent spread

14
MRSA Isolates From ICUs vs Non-ICUs
Fridkin. Clin Chest Med. 199920(2)303.
ICUintensive care unit
15
Failure To Prevent MRSA Spread

• Thompson et al. found that despite isolation of
  patients known to have MRSA from clinical
  cultures, the prevalence of MRSA infection
  continued to increase.

Thompson RL, Ann Intern Med 198297309
16
Control of MRSA Using Active Surveillance
Cultures and Isolation of Colonized Patients
Cases
Date
Incidence ( p lt 0.002) and Prevalence (p lt 0.001)
Thompson RL, Ann Intern Med 198297309.
17
MRSA (which had been out of control for 2.5
years) Was Completely Eradicated from the Hospital
Within 1.5 years This was done with no antibiotic
control effort of any kind. There was also no
campaign to increase hand hygiene.
18
Reservoir for the Spread of Antibiotic Resistant
Pathogens
Recognized by results of Clinical Microbiology
Cultures
Colonized Patients
19
CDC Guideline for Isolation Precautions

• The CDC guideline for isolation precautions
  recommends contact isolation for patients known
  or suspected to be colonized or infected with
  epidemiologically important antibiotic-resistant
  microorganisms.

Garner, et al. ICHE 19961753.
20
Prevalence of MRSA Colonization During the
Outbreak
Jernigan JA, et al. Am J Epi 1996143496-504.
21
Follow-up After Control of MRSA Outbreak in NICU
No MRSA in any patient during the next 10 years
and about 100,000 patient-days. This suggests a
low frequency of de novo development of
methicillin resistance despite prolonged hospital
stay and frequent antibiotic therapy in the NICU.
It also suggests a very low rate of MRSA
colonization among NICU workers and mothers in
central Virginia.
22
Criteria for Causal Inference

• Strength of association
• 2. Consistency of evidence
• 3.Temporal relationship
• 4. Biological gradient
• 5. Reversibility
• 6. Specificity
• 7. Coherence of evidence

Hill AB. A Short Textbook of Medical Statistics
(11th ed.), p. 273. London, UK Unibooks. 1984.

23
Studies Reporting Control of MRSA Using ASC CP
Haley RW, et al. J Infect Dis 1995
171614-624. Jernigan JA, et al. Am J Epidemiol
1996 143496-504. Salmenlinna S, et al. Euro J
Clin Micro Infect Dis 2000 19101-107. Vriens
MR, et al, ICHE 2002 23491-494. Thompson R, et
al. Ann Intern Med 1982 97309-317. Jernigan J
et al, ICHE 1995 16686-696. Jans B, et al, ICHE
2000 21419. Harbarth S, et al. J Hosp Infect
2000 4643-49. Back NA, et al, ICHE 1996
17227-231. Calfee DP, et al, ICHE 2002
23407-410.
24
Studies Reporting Control of MRSA Using ASC CP
Chaix C, et al. JAMA 1999 2821745-51. Law MR,
et al. Epidemiol Infect 1988 101623-629. Murray-
Leisure KA, et al, ICHE 1990 11343-350. Nicolle
LE, et al ICHE 1999 20202 -205. Cantey J, et
al. SHEA. 2002 Abstract 3649. Croyle K, et al,
SHEA. 2002 Abstract 3549. Kotilainen P, et al.
Arch Intern Med 2001 161859-863. Nouer A, et al
ICAAC 2002 K-97 97. Horcajada J, et al ICAAC
2002K-98. Gerard M, et al ICAAC
2002K-99. Verhoef J, et al. Eur J Clin Micro
Infect Dis 1999 18461-466. Cooper CL et al,
ICHE 200223483-484.
25
Publications From Northern European Countries
Reporting Control of MRSA To A Very Low
Prevalence Using ASC CP
Verhoef J, et al. Eur J Clin Micro Infect Dis
1999 18461-466. Salmenlinna S, et al. Euro J
Clin Micro Infect Dis 2000 19101-107. Bager
F. DANMAP 98. www.svs.dk/dk/z/Danmap201998.pd
1999. Vriens MR, et al, ICHE 2002
23491-494.  
26
Antimicrobial Resistance Surveillance in
Staphylococcus aureus blood isolates, Denmark,
1960-1995
Staphylococcus aureus Antimicrobial Resistance
Year
Source DANMAP Report, 1997.
27
Haley RW et al, JID 1995171614-624.
28
Percentage of Nosocomial Enterococci Reported as
Resistant to Vancomycin, by Year
National Nosocomial Infections Surveillance
(NNIS) System Data, 1989-1999.
29
Byers KE et al. ICHE 200122140-7.
30
Follow-up After Control of VRE in ICU Reaching
100 Prevalence Early in Outbreak
Prevalence rapidly decreased to 0. No VRE
isolated from any patient in the ICU during the
next year despite weekly cultures of all patients
at risk and the lack of an antibiotic control
program. This suggests a low frequency of de novo
mutation to vancomycin resistance despite
prolonged hospital stay and frequent antibiotic
therapy.
31
Relationship Between Antibiotic Therapy and
Development of VRE Culture Positivity

• Antibiotics alone will not select for VRE if
  resistant bacteria are not already present or if
  a patient does not come into contact with them.

Murray BE. NEJM 2000342710-721.
32
Control of VRE with Active Surveillance Cultures
and Contact Isolation in California Hospital
33
COST-EFFECTIVENESS OF PREVENTING VRE INFECTIONS

• Expanded control measures including active
  surveillance cultures and contact isolation to
  prevent spread of VRE resulted in hospital
  savings of 189,318 per year1 (despite a high
  prevalence and polyclonality2 of the VRE
  isolates).

1) Montecalvo MA, et al. ICHE 2001
July22437-42. 2) Montecalvo MA, et al. ICHE
1995 Dec16680-85.
34
Week 45
40
60
0
20
Muto CA, et al. IDSA 2001, abstract 210, p. 75.
35
VRE Prevalence in 30 Healthcare Facilities,
Siouxland, 1997 vs 1999
Ostrowsky BE, et al., NEJM 20013441427-1433.
36
VRE and MRSA Bacteremias at Hospitals of
Comparable Size and Complexity, 1999
Calfee DP, et al. ICHE 200223407-410.
37
Studies Reporting Control of VRE Using ASC CP
Boyce JM, et al, ICHE 1995 16634-637. Boyce JM,
et al. J Clin Microbiol 1994 321148-1153. Livorn
ese LL, et al. Ann Intern Med 1992
117112-116. Byers KE, et al, ICHE 2001
22140-147. Ostrowsky BE, et al. N Engl J Med
2001 3441427-1433. Calfee DP, et al, ICHE 2002
23407-410. Karanfil LV, et al, ICHE 1992
13195-200. Montecalvo MA, et al. Antimicrob
Agents Chemother 1994 381363-1367. Dembry L, et
al, ICHE 1996 17286-292. Rupp ME, et al, ICHE
2001 22301-303.                    
38
Studies Reporting Control of VRE Using ASC CP
Malik RK, et al. Pediatric Infect Dis J 1999
18352-356. Muto CA, et al, SHEA 1998 Abstract
no 7638. Rubin LG, et al, ICHE 1992
13700-705. Jochimsen E, et al, ICHE 1999
20106-109. Golan Y, et al, IDSA 2001
20975. Price CS, et al, IDSA 2001
21275. Siddiqui AH, et al. AJIC 2002
3040-43. Calfee DP, et al, IDSA. 2000 Abstract
2144. Muto CA, et al, ICHE 2002
23429-435. Christiansen K, et al, ICAAC 2002,
abstract K-660, page 317. Muto CA, et al,
abstract 164, SHEA 2002, page 80.              
     
39
Studies Reporting Control of VRE Using ASC CP
Incidence Rate Ratio 95 CI P value
Comparison
2 vs 1 2 vs 3 4 vs 3
0.63 0.38-1.05 0.078 0.36
0.23-0.55 lt0.0005 0.68
0.54-0.85 lt0.0005
Siddiqui AH, et al. AJIC 2002 3040-43.
40
STUDIES REPORTING FAILURE OF INFECTION CONTROL
MEASURES TO CONTROL VRE
of Wards on which Active Surveillance Cultures
were Used Study Wards of Hospital
Beds 1 1 lt3 2
2 lt5 3 4 ?
Slaughter Ann Int Med 1996125448.Morris Ann
Int Med 1995123250.Goetz, et al. AJIC
199826558.
41
Could Hand Hygiene Alone Control MRSA Like This?
Staphylococcus aureus Antimicrobial Resistance
Year
Source DANMAP Report, 1997.
42
Rates of MRSA Transmission
Jernigan, et al. Am J Epi 1996143496-504.
43
Rates of Clonal MRSA Transmission
Unisolated Isolated
Transmissions
38 1
Assumed person days at risk
X X
acquiring MRSA clone from 3 unisolated ICU
patients (i.e., 23 patients and 15 HCWs)
acquiring MRSA clone from 3 isolated ICU
patients
RR38.0, 95 CI6.4-1539.9, plt10-6
Vriens MR, et al, ICHE 2002 23491-494.
44
Conditional Logistic Regression Analysis
Variable OR P Proximity to
unisolated 2.04 0.0014 VRE patients History
of major trauma 9.27 0.020 Metronidazole
therapy 3.04 0.040 Per exposure-unit
Byers KE et al. ICHE 200122140-7.
45
MRSA Isolates From ICUs vs Non-ICUs
SP
UP
Fridkin. Clin Chest Med. 199920(2)303.
ICUintensive care unit
46
Percentage of Nosocomial Enterococci Reported as
Resistant to Vancomycin, by Year
SP
UP
National Nosocomial Infections Surveillance
(NNIS) System Data, 1989-1999.
47
ISOLATION GOWNS PREVENT HCWs FROM CONTAMINATING
THEIR CLOTHES/HANDS
14 (40) of 35 HCWs gowns were culture () for
MRSA and ARE on exiting room (2-200 colonies
recovered). Clothing underneath was culture (-).
11 (69) of 16 HCWs wearing freshly laundered
white coats had detectable contamination. 3 of
11 developed () hand cultures after touching the
white coat.
Boyce, et al. SHEA 1998, Abstract S74.
48
CONTAMINATION OF GOWNS, GLOVES AND STETHOSCOPES

• Two thirds of examinations of VRE patients
  resulted in VRE contamination of gown, gloves
  and/or stethoscopes.
• Same rate of contamination whether the patient
  was infected or merely colonized.

Zachary KC et al. ICHE 2001 22560-564.
49
Importance of Gowns for Controlling Contact
Transmission of VRE
Gloves Gown gloves
VRE Rate per 100 patient-days 3.78
1.8
p0.04 In a proportional
hazards model adjusted for length of stay,
gloves only precautions were associated with a
hazard ratio of 2.5, p0.02, 95CI1.2-5.3)
Srinivasan A, et al, ICHE 2002 23424-428.
50
Importance of Gowns for Controlling Contact
Transmission of VRE
Gloves Gown gloves
VRE Rate per 1000 patient-days 19.6
9.1
plt0.01 In a logistic
regression analysis, gown and gloves
precautions were associated with an adjusted odds
ratio of 0.43, p0.02, 95CI0.27-0.68)
Puzniak LA, et al, Clin Infect Dis 2002
3518-25.
51
Environmental MRSA Contamination

• 70 of rooms had environmental contamination when
  the patient was colonized or infected and 42 of
  nurses gloves were contaminated after touching
  environmental surfaces without touching patient.1
• 7 of stethoscopes were contaminated with MRSA2
• Wiping with 70 isopropyl alcohol significantly
  reduced colony counts on stethoscopes (p lt
  0.02).3
• Contaminated surfaces include patients gowns,
  floor, bed linens, blood pressure cuffs, overbed
  tables, stethoscopes, etc.1

1Boyce. Infect Control Hosp Epidemiol.
199718622. 2 Cohen. Fam Pract. 199714446 3
Marinella. Arch Intern Med. 1997157786.
52
Rates of Persistent Environmental VRE
Contamination
Conventional 60/376 15.9 Bucket 0/135 0
Chi Square 25.7 p lt 0.001
Byers KE et al. ICHE 199819261-4.
53
Sensitivity of Using Clinical Microbiology
Cultures To Detect Hospital Patients Colonized
With MRSA

• Of 437 patients found to be colonized with MRSA
  on hospital admission, 66 had positive clinical
  microbiology cultures for MRSA during the
  hospital stay (15, 95CI 11.9-18.8).
• 306 (70) had 1,238 clinical microbiology
  cultures done during their admission and 98
  (7.9, 95CI 6.5-9.6) were positive for MRSA.

Salgado CD et al. SHEA 2003 abstract 28, p. 61.
54
Excess Cost of MRSA Infection
MRSA infections cost significantly more than MSSA
infections.
Kaye KS et al, ICAAC 2002 http//www.asm.org Engem
ann J et al, ICAAC 2001 abst. K-2056, p.
441. Cosgrove SE et al, ICAAC 2001 abst. K-1221,
p. 415. Abramson, ICHE 199920408. Wakefield,
AJIC 198816185-192. Cheng, J Hosp Infect
19881291-101.
55
The Estimated National Impact of Allowing a
Higher Rate of Nosocomial MRSA Infections

• A mathematical model found that current excess
  costs from having MRSA as 40 of all nosocomial
  S. aureus infections is that S. aureus infections
  cost the nation 14 more (149 million) than if
  this were not so.
• If MRSA were controlled to a low level as in
  Northern Europe, this excess cost would decrease
  to only 0.2 (1.9 million).
• If MRSA continues to increase, however, and
  reaches a prevalence of 85 of S. aureus
  infections, then this estimated excess cost will
  increase to 25 (317 MM)

Lyle CT et al. SHEA 2003 abstract 101, p. 76.
56
Updated Cost Estimates

• More recent controlled studies have yielded
  estimates of cost for BSI more than 10-fold
  greater than the CDCs 1992 estimate, which was
  based on an uncontrolled study from the mid-1970s
  that contained only 8 cases of BSI. It is thus
  possible that this analysis may greatly
  underestimate the true excess national cost due
  to MRSA infections.
• At todays levels of MRSA prevalence, a 149
  million MR burden could thus actually exceed 1.5
  billion.

• Lyle CT et al. SHEA 2003 abstract 101, p. 76.
  Haley RW et al, Am J Med 1981 7051-58.
• Pittet D, et al, JAMA 1994 271 1598-601.
• Rello J et al, Am J Respir Crit Care Med
  20001621027-30.
• Dimick JB, et al Arch Surg 2001136229-34.

57
Attributable Mortality of MRSA Bacteremia

• Association with death was almost two-fold higher
  for MRSA bloodstream infections than for MSSA BSI
  (OR1.9, 95 CI, 1.5,2.4, p lt 0.001) after
  adjustment for severity of illness in a recent
  meta-analysis.

Cosgrove SE et al. Clin Infect Dis 2003 3653-59.
58
Costs Of VRE Bacteremia

• VRE bacteremia associated with significant
  increases in length of stay (p0.004), and
  hospital costs (more than 27,000 per episode,
  p0.04).1
• VRE BSI associated with 19-day increase in length
  of stay (plt0.001), and increased hospital costs
  (79,589 per episode, plt0.001).2

1) Stosor V, et al., Arch Int Med
1998158522. 2) Song X, et al, ICHE
200324251-256.
59
Attributable Morbidity and Mortality Of VRE
Bacteremia A Meta-analysis

• Compared to VSE, available data suggest that VRE
  bacteremia has
• higher rates of recurrence
• 16.9 vs. 3.7 plt0.0001
• higher case fatality rates
• RR2.57 95CI 2.27-2.91
• higher mortality due to bacteremia per se
• RR1.79 95CI 1.28-2.50

Salgado, CD. SHEA 2002, Abstract 113.
60
Studies Comparing VRE and VSE Bacteremic Patients
Matched for Severity of Illness
 
Patients matched by APACHE II Score Patients
matched by other severity of illness score
Salgado, CD. SHEA 2002, Abstract 113.
61
Transfer of Vancomycin Resistance from VRE to S.
aureus

• Documented in vitro and in vivo.

Noble, FEMS Microbiology Letters, 1992195-198.
Clinical Isolates of VRSA

• Anonymous. Staphylococcus aureus resistant to
  vancomycinUnited States, 2002. MMWR
  200251565-567.
• Anonymous. Public Health Dispatch
  Vancomycin-Resistant Staphylococcus aureus ---
  Pennsylvania, 2002 MMWR 200251902-3.

62
Studies Showing Cost Benefit of ASC CP
forControlling MRSA VRE
Jernigan JA, et al. ICHE 199516686. Papia G,
et al. ICHE 199920473-477. Chaix, et al. JAMA
19992821745. Montecalvo MA, et al. ICHE 2001
July22437-42. Bronstein M, et al. SHEA 2002
abstract 47, page 51. Karchmer TB et al, J Hosp
Infect 200251126. Muto CA et al, ICHE
200223429-435. Calfee DP, et al. ICHE
200223407-410. Lucet J et al. Arch Int Med
2003163181-88.
63
A Recent Study Reporting Cost Effectiveness of
Active Surveillance Cultures and Contact
Precautions for Controlling MRSA Spread
Baseline ASC CP
MRSA Rate per 1000 patient-days 5.4
1.8 Gown usage per patient-day
6.9 4.6
p0.10, plt0.001 Gown
costs decreased from 18,941 to 11,877.
Bronstein M, et al. SHEA 2002 abstract 47, page
51.
64
Are There Any Studies Showing No Cost Benefit of
ASC CP for Controlling MRSA VRE?
65
MRSA Isolates From ICUs vs Non-ICUs
Fridkin. Clin Chest Med. 199920(2)303.
ICUintensive care unit
66
Antimicrobial Resistance Surveillance in
Staphylococcus aureus blood isolates, Denmark,
1960-1995
Staphylococcus aureus Antimicrobial Resistance
Year
Source DANMAP Report, 1997.
67
This proactive approach has been recommended in a
guideline recently published by the Society for
Healthcare Epidemiology of America. It is posted
on the 'Position Paper' section of the SHEA
website (http//www.shea-online.org/PositionPapers
.html) where you are welcome to access it and
print a personal copy from your computer. Muto
et al. SHEA Guideline for Preventing Nosocomial
Transmission of Multidrug-resistant Strains of
Staphylococcus aureus and Enterococcus. Infect
Control Hosp Epidemiol 200324362-386.