Controlling MRSA and VRE: Is It Important to Identify the Reservoir? Barry M. Farr, MD, MSc Hospital Epidemiologist The William S. Jordan Jr. Professor.

Controlling MRSA and VRE: Is It Important to Identify the Reservoir?

Barry M. Farr, MD, MScHospital 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 Teleclasswww.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 Inference1. 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 %

1946 13%

1947 38%

1948 59%

Trends of prevalence rates for penicillinase-producing MSSA in hospitals and the community

0

10

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40

50

60

70

80

90

100

Year

% R

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Hospital Community

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.

Natural Selection

Mechanisms Of Developing Antibiotic Resistance

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

3rd gen. Ceph. 65% 50% 0.092

Aminoglycoside 45% 39% 0.492aminoglyco side

VRE Incidence Week

Hospital 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 2001;22(3):140-147.

Transmission Of IndividualClones 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.

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1989 1990 1991 1992 1993 1994 1995 1996 1997 1999

Year

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Non-ICU ICU

Fridkin. Fridkin. Clin Chest MedClin Chest Med. 1999;20(2):303. 1999;20(2):303..Fridkin. Fridkin. Clin Chest MedClin Chest Med. 1999;20(2):303. 1999;20(2):303..ICU=intensive care unitICU=intensive care unitICU=intensive care unitICU=intensive care unit

MRSA Isolates From ICUs vs Non-MRSA Isolates From ICUs vs Non-ICUsICUs


Failure To Prevent MRSA Spread

1977 1979 1980

Pneumonia 0% 19% 24%

Blood stream infection

0% 13% 40%

Surgical site infection

0% 27% 49%

• 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 1982;97:309

0

5

10

15

20

25

30

35

D-80 J-81 F-81 M-81 A-81 M-81 J-81 J-81 A-81 S-81 O-81 N-81

New Cases Prevalence

Date

Cas

es

Incidence ( p < 0.002) and Prevalence (p < 0.001)

Control of MRSA Using Active Surveillance Cultures and Contact Precautions

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

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1

2

3

4

5

6

7

8

July Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun

1991 1992

Nu

mb

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of

Co

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ts

= Index Case

= Acquired MRSA from unisolated patient

= Acquired MRSA from isolated infant

Follow-up After Control of MRSA Outbreak in NICURSA 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 ControlFirst 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.

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.

Studies Reporting Control of MRSA 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.


Publications From Northern European Countries Reporting Control of MRSA To A Very Low Prevalence Using ASC & CP

http://www.svs.dk/dk/z/Danmap%201998.pd

Methicillin

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

60 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

Penicillin

Tetracycline

Fusidic AcidGentamicinCiprofloxacin

Erythromycin

Year

Antimicrobial Resistance Surveillance in Staphylococcus aureus blood isolates, Denmark, 1960-1995

Source: DANMAP Report, 1997.

Stap

hyl

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cus

aure

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HaleyRW et al, JID 1995;171:614-624.

0

5

10

15

20

25

30

89 90 91 92 93 94 95 96 97 98 99

Year

% V

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mycin

-Resis

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nte

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Percentage of Nosocomial Enterococci Reported as Resistant to Vancomycin,

by Year

*National Nosocomial Infections Surveillance (NNIS) System Data, 1989-1999.

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

50%

55%

60%

65%

70%

75%

80%

85%

90%

95%

100%

Week

Com

plia

nce

rate

0%

5%

10%

15%

20%

25%

30%

35%

VR

E p

ositi

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rat

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COMP RATE POS RATE Linear (POS RATE) Linear (COMP RATE)

Week 45

0 20

40 60

Muto CA, et al. IDSA 2001, abstract 210, p. 75.

VRE Prevalence in 30 Healthcare Facilities, Siouxland, 1997 vs 1999

Facility Number (%) VRE-Colonized 1997 1999 Relative p-value Risk

All 40 (2.2) 9 (0.5) 0.23 <0.001

Acute Care 10 (6.6) 0 0 <0.001

Long-TermCare

30 (1.8) 9 (0.5) 0.31 0.001

Ostrowsky BE, et al., NEJM 2001;344:1427-1433.

MRSA BSI

VRE BSI

A B C D E F UVA

Hospital

No

. o

f B

SI

in 1

99

9VRE and MRSA Bacteremias at Hospitals of

Comparable Size and Complexity, 1999

Calfee DP,et al.ICHE 2002;23:407-410.

Studies Reporting Control of VRE Using ASC & CPBoyce 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: # Wards: % of Hospital Beds:

1 0 0% 2 1 <3% 3 2 <5% 4 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.

Source of New VRE Cases in a Hospital with a High VRE Prevalence and Polyclonality

Molecular epidemiologic analysis showed that establishmentof 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.

Methicillin

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

60 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

Penicillin

Tetracycline


Erythromycin

Year

Could Hand Hygiene Alone Control MRSA Like This?


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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 5 10

Patient-days 558 71.5

Rates 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 TransmissionUnisolated Isolated

Transmissions *^

Assumed person days at risk X X

RR=38.0, 95% CI=6.4-1539.9, p<10-6

*= # acquiring MRSA clone from 3 unisolated ICU patients (i.e., 23 patients and 15 HCWs)

^= # acquiring MRSA clone from 3 isolated ICU patients


Conditional Logistic Regression Analysis

Variable OR P

Proximity to unisolated 2.04* 0.0014VRE patients

History of major trauma 9.27 0.020

Metronidazole therapy 3.04 0.040

* Per exposure-unit


0

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60

1989 1990 1991 1992 1993 1994 1995 1996 1997 1999

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Non-ICU ICU




UPSP

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89 90 91 92 93 94 95 96 97 98 99

Year

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Percentage of Nosocomial Enterococci Reported as Resistant to Vancomycin,

by Year

*National Nosocomial Infections Surveillance (NNIS) System Data, 1989-1999.

UP SP

ISOLATION GOWNS PREVENT HCWs FROM CONTAMINATING THEIR

CLOTHES/HANDS14 (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

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)

Gloves Gown & gloves

Srinivasan A, et al, ICHE 2002; 23:424-428.

Importance of Gowns for Controlling Contact Transmission of VRE

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)

Gloves Gown & gloves

Puzniak LA, et al, Clin Infect Dis 2002; 35:18-25.

11Boyce. Boyce. Infect Control Hosp Epidemiol.Infect Control Hosp Epidemiol. 1997;18:622.1997;18:622.2 2 Cohen. Cohen. Fam PractFam Pract. 1997;14:446. 1997;14:4463 3 Marinella. Marinella. Arch Intern MedArch Intern Med. 1997;157:786. 1997;157:786..

11Boyce. Boyce. Infect Control Hosp Epidemiol.Infect Control Hosp Epidemiol. 1997;18:622.1997;18:622.2 2 Cohen. Cohen. Fam PractFam Pract. 1997;14:446. 1997;14:4463 3 Marinella. Marinella. Arch Intern MedArch Intern Med. 1997;157:786. 1997;157:786..

Environmental MRSA ContaminationEnvironmental MRSA ContaminationEnvironmental MRSA ContaminationEnvironmental MRSA Contamination• 70% of rooms had environmental contamination 70% of rooms had environmental contamination

when the patient was colonized or infected and 42% when the patient was colonized or infected and 42% of nurses’ gloves were contaminated after touching of nurses’ gloves were contaminated after touching environmental surfaces without touching patient.environmental surfaces without touching patient.11

• 7% of stethoscopes were contaminated with MRSA7% of stethoscopes were contaminated with MRSA22

– Wiping with 70% isopropyl alcohol significantly reduced Wiping with 70% isopropyl alcohol significantly reduced colony counts on stethoscopes (p < 0.02).colony counts on stethoscopes (p < 0.02).33

• Contaminated surfaces include patient’s gowns, Contaminated surfaces include patient’s gowns, floor, bed linens, blood pressure cuffs, overbed floor, bed linens, blood pressure cuffs, overbed tables, stethoscopes, etc.tables, stethoscopes, etc.11

• 70% of rooms had environmental contamination 70% of rooms had environmental contamination when the patient was colonized or infected and 42% when the patient was colonized or infected and 42% of nurses’ gloves were contaminated after touching of nurses’ gloves were contaminated after touching environmental surfaces without touching patient.environmental surfaces without touching patient.11

• 7% of stethoscopes were contaminated with MRSA7% of stethoscopes were contaminated with MRSA22

– Wiping with 70% isopropyl alcohol significantly reduced Wiping with 70% isopropyl alcohol significantly reduced colony counts on stethoscopes (p < 0.02).colony counts on stethoscopes (p < 0.02).33

• Contaminated surfaces include patient’s gowns, Contaminated surfaces include patient’s gowns, floor, bed linens, blood pressure cuffs, overbed floor, bed linens, blood pressure cuffs, overbed tables, stethoscopes, etc.tables, stethoscopes, etc.11

Rates of Persistent Environmental VRE Contamination

Conventional 60/376 = 15.9%

Bucket 0/135 = 0%

Chi Square = 25.7

p < 0.001


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 MRSA Nosocomial Bloodstream

Infections

MSSA MRSA P-value

Attributable excess lengthof stay median, days

4 12 0.023

Attributable total costmedian

$9,661 $27,083 0.043

Attributable variable directcost median

$4,989 $14,783 0.043

Abramson, ICHE 1999;20:408.

•Association with death was almost two-fold Association with death was almost two-fold higher for MRSA bloodstream infections than for higher for MRSA bloodstream infections than for MSSA BSI (OR=1.9, 95% CI, 1.5,2.4, pMSSA BSI (OR=1.9, 95% CI, 1.5,2.4, p < 0.001) < 0.001) after adjustment for severity of illness in a recent after adjustment for severity of illness in a recent meta-analysis.meta-analysis.

Cosgrove. SHEA 2001. Abstract #96Cosgrove. SHEA 2001. Abstract #96..

Attributable Mortality of MRSA Bacteremia

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

Vancomycintreatment

14.5 1.43-145.6

RespiratoryDistress

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 Compared to VSE, available data suggest

that VRE bacteremia has:that VRE bacteremia has: higher rates of recurrencehigher rates of recurrence

16.9% vs. 3.7% 16.9% vs. 3.7% pp<0.0001<0.0001 higher case fatality rateshigher case fatality rates

RR=2.57 [95%CI= 2.27-2.91]RR=2.57 [95%CI= 2.27-2.91] higher mortality due to bacteremia per sehigher mortality due to bacteremia per se

RR=1.79 [95%CI= 1.28-2.50]RR=1.79 [95%CI= 1.28-2.50]

Salgado, CD. SHEA 2002, Abstract #113.Salgado, CD. SHEA 2002, Abstract #113.

Studies Comparing VRE and VSE Studies Comparing VRE and VSE Bacteremic Patients Matched for Bacteremic Patients Matched for

Severity of IllnessSeverity of Illness

STUDY SAMPLE SIZE

CASE FATALITY RATE (%) ATTRIBUTABLE MORTALITY

*Jernigan J. IDSA 1996;Pg 219

13 VRE BSI 7 VSE BSI

VRE VSE 6/13(46) 0/7(0) p=.05

46%

**Stosor V. Arch IM 1998;158


VRE VSE 8/21(38) 3/32(9) p=.01

29%

*Lodise T. CID 2002;34


VRE VSE 20/53(38) 11/53 (21) p=.05

17%

**Patients matched by APACHE II ScorePatients matched by APACHE II Score****Patients matched by other severity of illness scorePatients matched by other severity of illness score


Multivariable Analyses of Mortality Risks Multivariable Analyses of Mortality Risks for Enterococcal Bacteremiafor Enterococcal Bacteremia

• Of 10 multivariate analyses of patients with Of 10 multivariate analyses of patients with enterococcal bacteremia, enterococcal bacteremia, – 3 reported no elevated risk of death associated 3 reported no elevated risk of death associated

with vancomycin resistancewith vancomycin resistance– 3 reported an elevated risk of death (OR=2 to 3) 3 reported an elevated risk of death (OR=2 to 3)

with vancomycin resistance that was not with vancomycin resistance that was not statistically significant but with wide 95% CIsstatistically significant but with wide 95% CIs

– 4 reported a significantly elevated risk of death 4 reported a significantly elevated risk of death (with similar Ors, 2 to 3). These 4 studies tended (with similar Ors, 2 to 3). These 4 studies tended to be larger and have greater statistical power to be larger and have greater statistical power than the negative studies. than the negative studies.


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 forControlling 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

MRSA BSI

VRE BSI

A B C D E F UVA

Hospital

No

. o

f B

SI

in 1

99

9VRE and MRSA Bacteremias at Hospitals of

Comparable Size and Complexity, 1999

Calfee DP,et al. ICHE 2002;23:407-410.

Cost Effectiveness of ASC & CP for Controlling Contact Transmission of MRSA

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.

Baseline ASC & CP

Bronstein M, et al. SHEA 2002 abstract 47, page 51.

0

10

20

30

40

50

60

1989 1990 1991 1992 1993 1994 1995 1996 1997 1999

Year

% S

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10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

60 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

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Erythromycin

Year



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Estimated Deaths Due To Antimicrobial Resistant Infections Compared With Deaths Due To Tuberculosis In The United States

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

1992 1993 1994 1995 1996 1997 1998 1999

Year

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ARI Deaths

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10%

20%

30%

40%

50%

60%

70%

80%

90%

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60 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

Penicillin

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Controlling MRSA and VRE: Is It Important to Identify the Reservoir?

Barry M. Farr, MD, MScHospital 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 Teleclasswww.webbertraining.com

.

Controlling MRSA and VRE: Is It Important to Identify the Reservoir? Barry M. Farr, MD, MSc Hospital Epidemiologist The William S. Jordan Jr. Professor.

Documents

susceptible host slide

control of mrsa

icu patients

isolation of patients

prevalence of mrsa infection

controlling mrsa

stepdown unit

isolation precautions