Transcript No Slide Title

Controlling MRSA and VRE: Is It
Important to Identify the Reservoir?
Barry M. Farr, MD, MSc
Hospital Epidemiologist
The William S. Jordan Jr. Professor of Medicine and Epidemiology
University of Virginia Health System
Charlottesville, VA
Hosted by Paul Webber
[email protected]
A Webber Training Teleclass
www.webbertraining.com
THE INFECTIOUS DISEASE PROCESS
1.
Etiologic agent
2.
Reservoir
3.
Portal of exit
4.
Method of transmission
5.
Portal of entry
6.
Susceptible host
Criteria for Causal Inference
1. 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.
Rapid Increase in the Prevalence of
Penicillin-resistant Staphylococcus
aureus, Hammersmith Hospital, London
1941
<1%
1946
13%
1947
38%
1948
59%
Trends of prevalence rates for penicillinaseproducing MSSA in hospitals and the community
100
90
80
60
50
40
30
20
10
Year
Hospital
Community
74
19
72
19
70
19
68
19
66
19
64
19
62
19
60
19
58
19
56
19
54
19
52
19
50
19
48
19
46
19
44
19
42
19
40
0
19
% Resistant
70
Mechanisms Of Developing
Antibiotic Resistance
1. Random genetic mutation.
2. Plasmid swapping during conjugation.
3. Movement of transposons to
plasmids/chromosomes.
4. Transduction by bacteriophages.
5. Transformation (acquisition of resistant genes
from a recently killed cell and incorporation into a
chromosome or plasmid).
6. Binary fission (replication) can share any of
the above.
Mechanisms Of Developing
Antibiotic Resistance
Natural Selection
Darwin C. On the Origin of Species by Means of
Natural Selection, London, 1859.
Prevalence of Antibiotic Therapy
in U.S. Hospitals In Recent Surveys
•Almost half of all patients
•Almost all ICU patients
Univariate Analysis Of Antibiotic
Exposure
Cases
Controls
p value
Vancomycin
46%
36%
0.219
Metronidazole
43%
21%
0.004
Clindamycin
31%
28%
0.755
Amp/sulbactam
27%
15%
0.073
Ticar/clav.
20%
14%
0.357
Imipenem
5%
4%
0.694
Ciprofloxacin
34%
24%
0.183
3 gen. Ceph.
65%
50%
0.092
Aminoglycoside
45%
39%
0.492
rd
aminoglyco side
VRE Incidence
Hospital Ward
Week
1
2
3
4
6th Floor
ICU
Step-down Unit
0
0
0
0
0
0
0
0
5th Floor
ICU
Step-down Unit
2
4
1
2
0
1
0
1
3rd Floor
ICU
Step-down Unit
1
6
1
3
1
0
0
1
Byers KE, et al. ICHE 2001;22(3):140-147.
Transmission Of Individual
Clones Of VRE
Boyce, J Cin Micro 1994;32:1148.
Dembry, SHEA 1994 Abstract #28.
Edmond, Clin Infect Dis 1995;20:1126.
Handwerger, Clin Infect Dis
1993;16:750.
Livornese, Ann Int Med 1992;117:112.
Montecalvo, Anti Ag Chemo
1994;38:1363.
Rubin, Infect Cont Hosp Epi
1992;13:700.
MRSA Isolates From ICUs vs NonICUs
Non-ICU
ICU
% S. aureus resistant to
methicillin
60
50
40
30
20
10
0
1989
1990
1991
1992
1993
1994
1995
1996
1997
1999
Year
ICU=intensive care unit
Fridkin. Clin Chest Med. 1999;20(2):303.
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.
Pneumonia
Blood stream
infection
Surgical site
infection
1977
1979
1980
0%
19%
24%
0%
13%
40%
0%
27%
49%
Thompson RL, Ann Intern Med 1982;97:309
Control of MRSA Using Active Surveillance
Cultures and Contact Precautions
New Cases
Prevalence
35
30
25
20
15
10
5
0
D-80 J-81
F-81 M-81 A-81 M-81 J-81
J-81
A-81
S-81 O-81 N-81
Date
Incidence ( p < 0.002) and Prevalence (p < 0.001)
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.
Reservoir for the Spread of
Antibiotic Resistant Pathogens
Recognized by
results of
Clinical
Microbiology
Cultures
Colonized Patients
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 1996;17:53
Prevalence of MRSA Colonization During
the Outbreak
8
= Index Case
Number of Colonized Patients
7
= Acquired MRSA from unisolated patient
6
= Acquired MRSA from isolated infant
5
4
3
2
1
0
July
1991
Aug
Sep
Oct
Nov
Dec
Jan
1992
Feb
Mar
Apr
May
Jun
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.
Control of 2 MRSA NICU Outbreaks
Using ASC and Barrier Precautions
Without Antibiotic Control
First outbreak in a 50-bed NICU controlled over
several months
32 colonized over 5 weeks
5 colonized infants (16%) became infected and
one died of MRSA BSI.
2nd outbreak of 14 colonized and 4 infected (29%)
(with another death due to MRSA BSI) controlled in
less than one month.
Back NA, et al. ICHE 1996;17:227-231.
Studies Reporting Control of MRSA
Using ASC & CP
Haley RW, et al. J Infect Dis 1995; 171:614-624.
Jernigan JA, et al. Am J Epidemiol 1996; 143:496-504.
Salmenlinna S, et al. Euro J Clin Micro & Infect Dis 2000;
19:101-107.
Vriens MR, et al, ICHE 2002; 23:491-494.
Thompson R, et al. Ann Intern Med 1982; 97:309-317.
Jernigan J et al, ICHE 1995; 16:686-696.
Jans B, et al, ICHE 2000; 21:419.
Harbarth S, et al. J Hosp Infect 2000; 46:43-49.
Back NA, et al, ICHE 1996; 17:227-231.
Calfee DP, et al, ICHE 2002; 23:407-410.
Studies Reporting Control of MRSA
Using ASC & CP
Chaix C, et al. JAMA 1999; 282:1745-51.
Law MR, et al. Epidemiol Infect 1988; 101:623-629.
Murray-Leisure KA, et al, ICHE 1990; 11:343-350.
Nicolle LE, et al ICHE 1999; 20:202 -205.
Cantey J, et al. SHEA. 2002; Abstract 36:49.
Croyle K, et al, SHEA. 2002; Abstract 35:49.
Kotilainen P, et al. Arch Intern Med 2001; 161:859-863.
Nouer A, et al ICAAC 2002; K-97: 97.
Horcajada J, et al ICAAC 2002:K-98.
Gerard M, et al ICAAC 2002:K-99.
Verhoef J, et al. Eur J Clin Micro Infect Dis 1999; 18:461-466.
Cooper CL et al, ICHE 2002;23:483-484.
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; 18:461-466.
Salmenlinna S, et al. Euro J Clin Micro & Infect Dis 2000;
19:101-107.
Bager F. DANMAP 98. www.svs.dk/dk/z/Danmap%201998.pd 1999.
Vriens MR, et al, ICHE 2002; 23:491-494.
Antimicrobial Resistance
Surveillance in Staphylococcus aureus
blood isolates, Denmark, 1960-1995
100%
90%
80%
Penicillin
70%
60%
50%
Tetracycline
Methicillin
40%
Fusidic Acid
Gentamicin
Ciprofloxacin
30%
20%
10%
0% 60
Erythromycin
61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96
Year
Source: DANMAP Report, 1997.
Haley RW et al, JID 1995;171:614-624.
% Vancomycin-Resistant
Enterococci
Percentage of Nosocomial Enterococci
Reported as Resistant to Vancomycin,
by Year
30
25
20
15
10
5
0
89 90 91 92 93 94 95 96 97 98 99
*National Nosocomial Infections
Surveillance (NNIS) System
Data, 1989-1999.
Year
Byers KE et al. ICHE 2001;22:140-7.
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.
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 2000;342:710-721.
Control of VRE with Active Surveillance Cultures
and Contact Isolation in California Hospital
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
July;22:437-42.
2) Montecalvo MA, et al. ICHE 1995
Dec;16:680-85.
VRE compliance and positivity rates
35%
Compliance rate
95%
30%
90%
85%
25%
80%
20%
75%
70%
15%
65%
10%
60%
5%
55%
50%
0%
Week
0
COMP RATE
20
POS RATE
40
Week 45 60
Linear (POS RATE)
Linear (COMP RATE)
Muto CA, et al. IDSA 2001, abstract 210, p. 75.
VRE positivity rate
100%
VRE Prevalence in 30 Healthcare
Facilities, Siouxland, 1997 vs 1999
Facility
All
Number (%) VRE-Colonized
1997
1999
Relative
Risk
40 (2.2) 9 (0.5)
0.23
Acute Care
10 (6.6)
0
0
Long-Term
Care
30 (1.8)
9 (0.5)
0.31
p-value
<0.001
<0.001
0.001
Ostrowsky BE, et al., NEJM 2001;344:1427-1433.
VRE and MRSA Bacteremias at Hospitals of
Comparable Size and Complexity, 1999
MRSA BSI
No. of BSI in 1999
VRE BSI
A
B
C
D
Hospital
E
F
UVA
Studies Reporting Control of VRE
Using ASC & CP
Boyce JM, et al, ICHE 1995; 16:634-637.
Boyce JM, et al. J Clin Microbiol 1994; 32:1148-1153.
Livornese LL, et al. Ann Intern Med 1992; 117:112-116.
Byers KE, et al, ICHE 2001; 22:140-147.
Ostrowsky BE, et al. N Engl J Med 2001; 344:1427-1433.
Calfee DP, et al, ICHE 2002; 23:407-410.
Karanfil LV, et al, ICHE 1992; 13:195-200.
Montecalvo MA, et al. Antimicrob Agents Chemother 1994;
38:1363-1367.
Dembry L, et al, ICHE 1996; 17:286-292.
Rupp ME, et al, ICHE 2001; 22:301-303.
Studies Reporting Control of VRE
Using ASC & CP
Malik RK, et al. Pediatric Infect Dis J 1999; 18:352-356.
Muto CA, et al, SHEA 1998; Abstract no 76:38.
Rubin LG, et al, ICHE 1992; 13:700-705.
Jochimsen E, et al, ICHE 1999; 20:106-109.
Golan Y, et al, IDSA 2001; 209:75.
Price CS, et al, IDSA 2001; 212:75.
Siddiqui AH, et al. AJIC 2002; 30:40-43.
Calfee DP, et al, IDSA. 2000; Abstract: 21:44.
Muto CA, et al, ICHE 2002; 23:429-435.
Christiansen K, et al, ICAAC 2002, abstract K-660, page 317.
Muto CA, et al, abstract 164, SHEA 2002, page 80.
STUDIES REPORTING FAILURE OF INFECTION
CONTROL MEASURES TO CONTROL VRE
# of Wards on which Active Surveillance Cultures
were Used:
Study:
Beds:
1
2
3
4
# Wards:
% of Hospital
0
1
2
4
Slaughter Ann Int Med 1996;125:448.
Morris Ann Int Med 1995;123:250.
Goetz, et al. AJIC 1998;26:558.
Quayle, et al. CID 1996;23:1020.
0%
<3%
<5%
?
Source of New VRE Cases in a Hospital with
a High VRE Prevalence and Polyclonality
Molecular epidemiologic analysis showed
that establishment of endemicity had been
mostly due to clonal spread with
accumulation of new strains over time.
Kim NJ et al. JID 1999;179:163.
Source of New VRE Cases in a Medical ICU
with a High VRE Prevalence and Polyclonality
The proportion of other patients with VRE
was the most important risk factor for new
patients becoming culture positive for VRE.
In multivariable analysis, this was a more
important predictor than other variables
found to be significant in univariate
analysis such as therapy with third
generation cephalosporins.
Bonten MJ et al. Arch Int Med 1998;158:1127.
VRE Polyclonality Due to Spread of
Transposons (i.e., despite patient to
patient spread)
Transposons (e.g., TN 5482) spread
from Enterococcus to Enterococcus
to chromosomes or plasmids by
conjugation.
de Lencastre H, et al. Microbial Drug
Resistance 1999;5:113.
Could Hand Hygiene Alone Control
MRSA Like This?
100%
90%
80%
Penicillin
70%
60%
50%
Tetracycline
Methicillin
40%
Fusidic Acid
Gentamicin
Ciprofloxacin
30%
20%
10%
0% 60
Erythromycin
61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96
Year
Source: DANMAP Report, 1997.
Can Hand Hygiene/ Standard
Precautions Control MRSA and VRE
Infections (i.e., without using ASC
and barrier precautions)?
1. Hand hygiene rates in most hospitals have not changed
since implementation of universal (standard)
precautions.
2. Pittet showed decrease in MRSA with increase in hand
hygiene, (Lancet 2000;356:1307-12.) but with much
bigger increase in ASC and CP for colonized patients.
(J Hosp Infect 2000;46:43-9. )
3. Larson reported significant 85% relative reduction in
VRE but 44% drop in control hospital and no significant
change in MRSA in intervention hospital despite
increase in hand hygiene. Behav Med 2000;26:14-22.
Can Hand Hygiene/ Standard Precautions
Control MRSA and VRE Infections?
4. Austin et al reported that 80% compliance with hand
hygiene would result in a relative reduction in VRE
prevalence of about 25% (PNAS 1999;96:6908-13). Much
better control was found with ASC and cohort isolation.
5. Sebille et al reported that increasing hand hygiene
compliance to 90% would only reduce MRSA prevalence
by 33%. They recommended ASC and CP
(ICHE 1997;18:84-92).
6. Some have claimed that switching to triclosan handwash
alone ended 2 MRSA NICU outbreaks, but both used
multiple measures and reported continuing “all IC
measures” (e.g., one used weekly ASC and and the other
used gowns, gloves, cohorting and bathing of every
neonate with triclosan). Webster J et al, J Paed Child
.
Health
1994;30:59-64. Zafar AB et al, AJIC 1995;3:200-8.
Can Hand Hygiene/ Standard Precautions
Control MRSA and VRE Infections?
7. Vernon reported decreases in MRSA and VRE in a LTCF
following a hand hygiene campaign with alcohol handrub
(Vernon MO et al IDSA 2001 abstract 249, p.82) but not in the
the other 2 healthcare facilities involved in the campaign.
(Vernon MO et al ICAAC 2001 abstract K-1331, p. 424.)
8. Gundlapalli reported increased VRE (not statistically
significant) after switching from ASC & CP to SP in an ICU
with a “multidimensional campaign to encourage strict
adherence” for 7 months but abstract did not comment on
control measures in the rest of the tertiary care hospital.
(Gundlapalli AV et al IDSA 2001 abstract 250, p. 82. )
9. Schultz reported an insignificant decline in VRE and no
change in MRSA or C. difficile after one year of a hand
hygiene campaign emphasizing use of an alcohol handrub.
(Schultz. ICAAC 2002, K-1099, p. 323.)
Rates of MRSA Transmission
Source
Isolated
Unisolated
Transmissions
Patient-days
Rates
5
10
558
71.5
0.009
0.140
RR=15.6, 95% CI=5.3-45.6, p<0.0001
Jernigan, et al. Am J Epi 1996;143:496-504.
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
RR=38.0, 95% CI=6.4-1539.9, p<10-6
Vriens MR, et al, ICHE 2002; 23:491-494.
Conditional Logistic Regression
Analysis
Variable
OR
P
Proximity to unisolated
VRE patients
2.04*
0.0014
History of major trauma
9.27
0.020
Metronidazole therapy
3.04
0.040
* Per exposure-unit
Byers KE et al. ICHE 2001;22:140-7.
MRSA Isolates From ICUs vs NonICUs
Non-ICU
ICU
% S. aureus resistant to
methicillin
60
50
40
SP
UP
30
20
10
0
1989
1990
1991
1992
1993
1994
1995
1996
1997
1999
Year
ICU=intensive care unit
Fridkin. Clin Chest Med. 1999;20(2):303.
% Vancomycin-Resistant
Enterococci
Percentage of Nosocomial Enterococci
Reported as Resistant to Vancomycin,
by Year
30
25
SP
UP
20
15
10
5
0
89 90 91 92 93 94 95 96 97 98 99
*National Nosocomial Infections
Surveillance (NNIS) System
Data, 1989-1999.
Year
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.
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. 4th Decennial Conference
on Nosocomial Infections, Atlanta, p. 75.
Importance of Gowns for Controlling
Contact Transmission of VRE
Gloves Gown & gloves
VRE Rate per 100 patient-days
3.78
1.8
p=0.04
In a proportional hazards model adjusted for length
of stay, ‘gloves only’ precautions were associated
with a hazard ratio of 2.5, p=0.02, 95%CI=1.2-5.3)
Srinivasan A, et al, ICHE 2002; 23:424-428.
Importance of Gowns for Controlling
Contact Transmission of VRE
Gloves Gown & gloves
VRE Rate per 1000 patient-days
19.6
9.1
p<0.01
In a logistic regression analysis, ‘gown and gloves’
precautions were associated with an adjusted odds
ratio of 0.43, p=0.02, 95%CI=0.27-0.68)
Puzniak LA, et al, Clin Infect Dis 2002; 35:18-25.
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 < 0.02).3
• Contaminated surfaces include patient’s gowns,
floor, bed linens, blood pressure cuffs, overbed
tables, stethoscopes, etc.1
1Boyce.
Infect Control Hosp Epidemiol.
1997;18:622.
2 Cohen. Fam Pract. 1997;14:446
3 Marinella. Arch Intern Med. 1997;157:786.
Rates of Persistent Environmental
VRE Contamination
Conventional
Bucket
60/376 = 15.9%
0/135 = 0%
Chi Square = 25.7
p < 0.001
Byers KE et al. ICHE 1998;19:261-4.
Excess Cost of MRSA Infection
MRSA infections cost significantly
more than MSSA infections.
Kaye KS et al, ICAAC 2002 http://www.asm.org
Engemann J et al, ICAAC 2001 abst. K-2056, p. 441.
Cosgrove SE et al, ICAAC 2001 abst. K-1221, p. 415.
Abramson, ICHE 1999;20:408.
Wakefield, AJIC 1988;16:185-192.
Cheng, J Hosp Infect 1988;12:91-101.
Comparison of Primary MSSA and MRS
Nosocomial Bloodstream Infections
MSSA
MRSA
P-value
4
12
0.023
Attributable total cost
median
$9,661
$27,083
0.043
Attributable variable direct
cost median
$4,989
$14,783
0.043
Attributable excess length
of stay median, days
Abramson, ICHE 1999;20:408.
Attributable Mortality of
MRSA Bacteremia
•Association with death was almost two-fold
higher for MRSA bloodstream infections than for
MSSA BSI (OR=1.9, 95% CI, 1.5,2.4, p < 0.001)
after adjustment for severity of illness in a recent
meta-analysis.
Cosgrove. SHEA 2001. Abstract #96.
Mortality with S. aureus Pneumonia
MRSA
54.5%
MSSA
2.6%
(RR=20.7, 95% CI=2.8-154)
Rello, Am J Resp Crit Care Med
1994;150:1545.
Factors Independently Associated with
Mortality Among Patients with Pneumonia
due to S. aureus
Factor
OR
95% CI
Septic Shock
61.5
5.63-672.2
Vancomycin
treatment
14.5
1.43-145.6
Respiratory
Distress
8.3
1.47-46.1
Gonzalez, et al. CID 1999;29:1171.
Costs Of VRE Bacteremia
•VRE bacteremia associated with significant
increases in length of stay (p=0.004), and
hospital costs (more than $27,000 per
episode, p=0.04).1
•VRE BSI associated with 19-day increase in
length of stay (p<0.001), and increased
hospital costs ($79,589 per episode, p<0.001).2
1) Stosor V, et al., Arch Int Med 1998;158:522.
2) Song X, et al, 37th IDSA, 1999, abstract 500, p
126.
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% p<0.0001
 higher case fatality rates
 RR=2.57 [95%CI= 2.27-2.91]
 higher mortality due to bacteremia per se
 RR=1.79 [95%CI= 1.28-2.50]
Salgado, CD. SHEA 2002, Abstract #113.
Studies Comparing VRE and VSE
Bacteremic Patients Matched for
Severity of Illness
STUDY
*Jernigan J. IDSA
1996;Pg 219
SAMPLE
SIZE
13 VRE BSI
7 VSE BSI
CASE FATALITY RATE (%)
ATTRIBUTABLE
MORTALITY
46%
VRE
VSE
6/13(46) 0/7(0) p=.05
**Stosor V. Arch IM
1998;158
21 VRE BSI
32 VSE BSI
VRE
VSE
8/21(38) 3/32(9) p=.01
29%
*Lodise T. CID
2002;34
53 VRE BSI
53 VSE BSI
VRE
VSE
20/53(38) 11/53 (21) p=.05
17%
*Patients matched by APACHE II Score
**Patients matched by other severity of illness score
Salgado, CD. SHEA 2002, Abstract #113.
Multivariable Analyses of Mortality Risks
for Enterococcal Bacteremia
• Of 10 multivariate analyses of patients with
enterococcal bacteremia,
– 3 reported no elevated risk of death associated
with vancomycin resistance
– 3 reported an elevated risk of death (OR=2 to 3)
with vancomycin resistance that was not
statistically significant but with wide 95% CIs
– 4 reported a significantly elevated risk of death
(with similar Ors, 2 to 3). These 4 studies tended
to be larger and have greater statistical power
than the negative studies.
Salgado, CD. SHEA 2002, Abstract #113.
VRE Infection Costs: A Meta-analysis
•VRE infection associated with significant
increases in attributable adjusted mortality
(OR=2.1,p=0.04) and hospital charges (mean
$12,766 per case) as compared with uninfected
patients .
•VRE infection associated with significant
increases in attributable adjusted mortality
(OR=2.5,p=0.05) and hospital charges (mean
$3,926 per case) as compared with patients
with infection due to vancomycin susceptible
enterococci.
Kaye KS et al, ICAAC 2002 http://www.asm.org
Transfer of Vancomycin
Resistance from VRE to S. aureus
•Documented in vitro and in vivo.
Noble, FEMS Microbiology Letters, 1992;195-198.
Clinical Isolates of VRSA
1) Anonymous. Staphylococcus aureus resistant to
vancomycin—United States, 2002. MMWR 2002;51:565-567.
2) Anonymous. Public Health Dispatch: Vancomycin-Resistant
Staphylococcus aureus --- Pennsylvania, 2002 MMWR
2002;51:902-3.
Studies Showing Cost Benefit of ASC & CP for
Controlling MRSA & VRE
Jernigan JA, et al. ICHE 1995;16:686.
Papia G, et al. ICHE 1999;20:473-477.
Chaix, et al. JAMA 1999;282:1745.
Montecalvo MA, et al. ICHE 2001 July;22:437-42.
Bronstein M, et al. SHEA 2002 abstract 47, page 51.
Karchmer TB et al, J Hosp Infect 2002;51:126.
Muto CA et al, ICHE 2002;23:429-435.
Calfee DP, et al. ICHE 2002;23:407-410.
Lucet J et al. Arch Int Med 2003;163:181-88.
Lyle CT et al. Abstract to be presented at SHEA 2003
Studies That Have Shown No Cost Benefit of ASC &
CP for Controlling MRSA & VRE
VRE and MRSA Bacteremias at Hospitals of
Comparable Size and Complexity, 1999
MRSA BSI
No. of BSI in 1999
VRE BSI
A
B
C
D
E
F
Hospital
Calfee DP, et al. ICHE 2002;23:407-410.
UVA
Cost Effectiveness of ASC & CP for
Controlling Contact Transmission of MRSA
Baseline
ASC & CP
MRSA Rate per 1000 patient-days
5.4^
1.8^
Gown usage per patient-day
6.9*
4.6*
^p=0.10, *p<0.001
Gown costs decreased from $18,941 to $11,877.
Bronstein M, et al. SHEA 2002 abstract 47, page 51.
MRSA Isolates From ICUs vs NonICUs
Non-ICU
ICU
% S. aureus resistant to
methicillin
60
50
40
30
20
10
0
1989
1990
1991
1992
1993
1994
1995
1996
1997
1999
Year
ICU=intensive care unit
Fridkin. Clin Chest Med. 1999;20(2):303.
Antimicrobial Resistance
Surveillance in Staphylococcus aureus
blood isolates, Denmark, 1960-1995
100%
90%
80%
Penicillin
70%
60%
50%
Tetracycline
Methicillin
40%
Fusidic Acid
Gentamicin
Ciprofloxacin
30%
20%
10%
0% 60
Erythromycin
61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96
Year
Source: DANMAP Report, 1997.
Estimated Deaths Due To Antimicrobial Resistant Infections
Compared With Deaths Due To Tuberculosis In The United States
18000
16000
14000
Number Of Deaths
12000
10000
TB Deaths
ARI Deaths
8000
6000
4000
2000
0
1992
1993
1994
1995
1996
Year
1997
1998
1999
Antimicrobial Resistance
Surveillance in Staphylococcus aureus
blood isolates, Denmark, 1960-1995
100%
90%
80%
Penicillin
70%
60%
50%
Tetracycline
Methicillin
40%
Fusidic Acid
Gentamicin
Ciprofloxacin
30%
20%
10%
0% 60
Erythromycin
61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96
Year
Source: DANMAP Report, 1997.
Controlling MRSA and VRE: Is It
Important to Identify the Reservoir?
.
Barry M. Farr, MD, MSc
Hospital Epidemiologist
The William S. Jordan Jr. Professor of Medicine and Epidemiology
University of Virginia Health System
Charlottesville, VA
Hosted by Paul Webber
[email protected]
A Webber Training Teleclass
www.webbertraining.com