Preventing the Spread of Vancomycin ResistanceA Report From the Hospital Infection Control Practices Advisory Committee Prepared by the Subcommittee on Prevention and Control of Antimicrobial-Resistant Microorganisms in Hospitals; Comment Period and Public Meeting

SUMMARY: This notice is a request for review and comment of the draft

document, Preventing the Spread of Vancomycin Resistance--A Report From

the Hospital Infection Control Practices Advisory Committee (HICPAC)

Prepared by the Subcommittee on Prevention and Control of

Antimicrobial-Resistant Microorganisms in Hospitals. The draft document

was prepared in collaboration with the National Center for Infectious

Diseases (NCID), CDC, and representatives of the American Hospital

Association, American Society for Microbiology, Association for

Professionals in Infection Control and Epidemiology, Infectious

Diseases Society of America, Society for Healthcare Epidemiology of

America, and Surgical Infection Society.

DATES: Written comments on the draft document must be received on or

before July 18, 1994.

ADDRESSES: Comments on this document should be submitted in writing to

the Centers for Disease Control and Prevention (CDC), Attention: VRE

Report Center, Mailstop A-07, 1600 Clifton Road, NE., Atlanta, Georgia

30333. The Federal Register containing this draft document may be

viewed and photocopied at most libraries designated as U.S. Government

Depository Libraries and at many other public and academic libraries

that receive the Federal Register throughout the country. In addition,

copies of this Federal Register notice document can be obtained by

calling (404) 332-2569.

FOR FURTHER INFORMATION CONTACT: The VRE Report Center, telephone (404)

332-2569.

SUPPLEMENTARY INFORMATION: A public meeting for an open discussion of

the draft document will be held at the CDC, Atlanta, Georgia, on June

15, 1994. Details about the meeting will be announced in a forthcoming

issue of the Federal Register.

Dated: May 11, 1994.

Claire V. Broome,

Acting Deputy Director, Centers for Disease Control and Prevention

(CDC).

Appendix--Preventing the Spread of Vancomycin Resistance-- A Report

from the Hospital Infection Control Practices Advisory Committee

Prepared by the Subcommittee on Prevention and Control of

Antimicrobial-Resistant Microorganisms in Hospitals

Executive Summary

This document contains recommendations for the prevention and

control of the spread of vancomycin resistance, with special focus on

vancomycin-resistant enterococci (VRE).

A rapid increase in the incidence of infection and colonization

with VRE has been reported from U.S. hospitals in the last 5 years.

This increase poses several problems, including (a) the lack of

available antimicrobial(s) for therapy of infections due to VRE, since

most VRE are also resistant to multiple other drugs, e.g.,

aminoglycoside and ampicillin, previously used for treatment of

infections due to these organisms; and (b) the possibility that the

vancomycin-resistance genes present in VRE may be transferred to other

gram-positive microorganisms such as Staphylococcus aureus.

An increased risk of VRE infection and colonization has been

associated with previous vancomycin and/or multi-antimicrobial therapy,

severe underlying diseases or immunosuppression, and cardio-thoracic or

intraabdominal surgery. Because enterococci can be found in the normal

gastrointestinal or female genital tracts, most enterococcal infections

have been attributed to endogenous sources within the individual

patient. However, recent reports of outbreaks and endemic infections

due to enterococci, including VRE, have shown that patient-to-patient

transmission of the microorganisms can occur either via direct contact

or indirectly via hands of personnel or contaminated patient-care

equipment or environmental surfaces.

Prevention and control of the spread of vancomycin resistance will

require concerted effort from various departments of the hospital, and

can only be achieved if each of the following elements is addressed:

(1) Education of hospital staff regarding the problem of vancomycin

resistance, (2) early detection and prompt reporting of vancomycin

resistance in enterococci and other gram-positive microorganisms by the

hospital microbiology laboratory, (3) implementation of appropriate

infection-control measures to prevent person-to-person transmission of

VRE, and (4) prudent vancomycin use by clinicians.

Introduction

From 1989 though 1993, the percentage of nosocomial enterococcal

infections reported to the CDC National Nosocomial Infections

Surveillance (NNIS) System that were resistant to vancomycin increased

from 0.3% to 7.9%.1 The increase was due mainly to the 34-fold

rise, from 0.4% to 13.6%, of infections due to VRE in intensive-care

unit (ICU) patients, although a trend towards increased vancomycin

resistance was also noted in non-ICU patients.1 The occurrence of

VRE in NNIS hospitals was directly associated with larger hospital size

(200 beds) and university affiliation.1 Other hospitals

also have reported increased endemic rates and clusters of VRE

infection and colonization.2-6 The actual increase in incidence of

VRE in U.S. hospitals may be larger because vancomycin resistance, in

particular moderate vancomycin resistance (as manifested in the VanB

phenotype), is not detected consistently with the automated methods

used in many clinical laboratories.7,8

Vancomycin resistance in enterococci has emerged amidst the

increasing incidence of high-level enterococcal resistance to

penicillin and aminoglycosides, thus presenting a serious challenge for

physicians treating patients with infections due to these

microorganisms.1,4 Treatment options are often limited to

combinations of antimicrobials or experimental compounds with unproven

efficacy.9

The epidemiology of VRE has not been well elucidated; however,

certain patient populations have been found to be at increased risk for

VRE infection or colonization; these include critically ill patients or

those with severe underlying disease or immunosuppression, such as ICU

patients or patients in the oncology or transplant wards; those who

have had an intra-abdominal or cardio-thoracic surgical procedure, or

indwelling urinary or central venous catheter; and those who have had

prolonged hospital stay or received multi-antimicrobial and/or

vancomycin therapy.2-6, CDC unpublished data Because enterococci

are part of the normal flora of the gastrointestinal and female genital

tracts, most infections with these microorganisms have been attributed

to the patient's endogenous flora.10 However, recent reports have

demonstrated that enterococci, including VRE, can spread by direct

patient-to-patient contact or indirectly via transient carriage on

hands of personnel11 or contaminated environmental surfaces and

patient-care equipment.12

In addition to the existing problem with VRE, the potential

emergence of vancomycin resistance in clinical isolates of S. aureus is

a serious public health concern. The vanA gene, which is frequently

plasmid-borne and confers high-level resistance to vancomycin, can be

transferred in vitro from enterococci to a variety of gram-positive

microorganisms,13,14 including Staphylococcus aureus.15

Although vancomycin resistance in clinical strains of S. epidermidis or

S. aureus has not been reported, a vancomycin-resistant clinical strain

of Staphylococcus haemolyticus has been isolated.16

In response to the dramatic increase in vancomycin resistance in

enterococci, the Subcommittee on the Prevention and Control of

Antimicrobial Resistant Microorganisms in Hospitals of the CDC's

Hospital Infection Control Practices Advisory Committee (HICPAC) held

meetings on November 14, 1993 and February 18, 1994, with

representatives from the American Hospital Association, American

Society for Microbiology, Association for Professionals in Infection

Control and Epidemiology, Infectious Diseases Society of America,

Society for Healthcare Epidemiology of America, and Surgical Infection

Society. The Subcommittee members agreed that prompt implementation of

control measures is needed and developed recommendations to prevent the

spread of VRE. The Subcommittee recognizes that data are limited and

considerable research will be required to elucidate fully the

epidemiology of VRE and determine cost-effective control strategies,

and many U.S. hospitals have concurrent problems with other

antimicrobial-resistant organisms, such as methicillin-resistant S.

aureus and beta-lactam and aminoglycoside-resistant gram-negative

bacilli, that may have different epidemiologic features and require

different control methods.

Recommendations

Hospital infection control programs, in collaboration with quality

improvement programs, microbiology laboratories, clinical departments,

and nursing, administrative, and housekeeping services, should develop

a comprehensive, institution-specific, strategic plan to detect,

prevent, and control infection and colonization with VRE. It is

strongly suggested that the following elements be addressed in the

plan.

I. Education Program

Continuing education programs for hospital staff should include

information concerning the epidemiology of VRE and the potential impact

of this pathogen on the cost and outcome of patient care. Because

detection and containment of VRE require a very aggressive approach and

high performance standards for hospital personnel, special awareness

and educational sessions may be indicated.

II. Role of the Microbiology Laboratory in the Detection, Reporting,

and Control of VRE

The microbiology laboratory is the first line of defense against

the spread of VRE in the hospital. The laboratory's ability to identify

enterococci and detect vancomycin resistance promptly and accurately is

essential in recognizing VRE colonization and infection and avoiding

complex, costly containment efforts that are required when recognition

of the problem is delayed. In addition, cooperation and communication

between the laboratory and the infection control program will

facilitate control efforts substantially.

A. Identification of enterococci: Presumptively identify colonies

on primary isolation plates as enterococci by using the colonial

morphology, Gram stain, and PYR test. Although identifying enterococci

to the species level can help predict certain resistance patterns

(e.g., E. faecium is more resistant to penicillin than E. faecalis) and

may help determine the epidemiologic relatedness of enterococcal

isolates, such identification is not essential if antimicrobial

susceptibility testing is performed.

B. Antimicrobial susceptibility testing: Determine vancomycin

resistance as well as high-level resistance to penicillin and

aminoglycosides\17\ for enterococci isolated from blood, sterile body

sites (with the possible exception of urine), and other sites as

clinically indicated. Evaluate the laboratory's method of

susceptibility testing, whether by automated microdilution or disk-

diffusion technique, for its ability to detect vancomycin resistance by

using E. faecalis ATCC 51299. This strain has a moderate level of

vancomycin resistance mediated by the vanB gene, which, unlike high-

level resistance mediated by vanA, is difficult to detect by most

methods used in clinical laboratories. Laboratories using disk

diffusion should incubate plates for 24 hours and read zones of

inhibition by using transmitted light.\17\,\18\ If testing as above

reveals that the method used by the laboratory is inadequate to detect

vancomycin resistance, the laboratory should perform either of the

following:

1. Streak 1 l of standard inoculum (0.5 McFarland) from an

isolated colony of enterococci onto BHI agar containing 6 g/ml

of vancomycin, and incubate the inoculated plate for 24 hours at 35

deg.C. Consider any growth indicative of vancomycin

resistance.\17\,\18\

2. Determine the minimum inhibitory concentration by agar dilution,

broth macrodilution, or manual broth microdilution.\17\,\18\

C. When VRE is isolated from a clinical specimen: 1. Confirm

vancomycin resistance by repeating antimicrobial susceptibility testing

using any of the recommended methods above, particularly if VRE

isolates are unusual in the hospital.

2. Immediately, while performing confirmatory susceptibility tests,

notify the patient's primary caregiver, patient-care personnel on the

ward on which the patient is hospitalized, and infection control

personnel regarding the presumptive identification of VRE, so that the

patient can be placed on appropriate isolation precautions promptly

(See Section III-A-4). Follow this preliminary report with the (final)

result of the confirmatory test. Additionally, highlight the report

regarding the isolate to alert staff that isolation precautions are

indicated.

D. Screening procedures for detecting VRE in hospitals where VRE

has not been detected: In many hospital microbiology laboratories,

antimicrobial susceptibility testing of enterococcal isolates from

urine or nonsterile body sites such as wounds is not performed

routinely; thus, recognition of nosocomial VRE colonization and

infection in hospitalized patients may be delayed. Therefore, in

hospitals where VRE has not yet been detected, special measures can

allow earlier detection of VRE.

1. Antimicrobial susceptibility survey. Perform periodic

susceptibility testing on enterococcal isolates recovered from all

types of clinical specimens, especially from high-risk patients, such

as those in an ICU or oncology or transplant ward. The optimal

frequency of testing and number of isolates to test are unknown and may

vary from hospital to hospital, depending on the hospital's patient

population and number of cultures performed. Hospitals processing large

numbers of culture specimens will need to test only a small fraction

(e.g., 10%) of enterococcal isolates every 1-2 months, whereas

hospitals processing fewer specimens may need to test all enterococcal

isolates during the survey period. The hospital epidemiologist can be

consulted to help design a suitable sampling strategy.

2. Culture survey of stools or rectal swabs. In tertiary medical

centers and other hospitals with many critically ill (e.g., ICU,

oncology, transplant) patients at high risk for VRE infection or

colonization, periodic culture surveys of stools or rectal-swabs of

such patients can detect the appearance of VRE. Fecal screening is

recommended before VRE infections have been identified clinically

because most patients colonized with VRE will have intestinal

colonization with this organism.\2\,\4\,\11\ The frequency and

intensity of surveillance should be based on the size of the population

at risk and the specific hospital unit(s) involved. If VRE have been

detected in other institutions in a hospital's area and/or if a

hospital wishes to determine whether VRE is present in the hospital

despite the absence of recognized clinical cases, stool or rectal-swab

culture surveys are very useful. The cost of screening can be reduced

greatly by inoculating specimens onto vancomycin-containing selective

media\2\,\12\ and restricting screening to those patients who have been

in the hospital long enough (e.g., 5-7 days) to have a substantial risk

of colonization, or who have been admitted from a facility, such as a

tertiary-care hospital or a chronic-care facility, where VRE is known

to be present. Once colonization with VRE has been detected, it would

be appropriate to begin to screen routinely all of the enterococcal

isolates from patients in the hospital (including those from urine and

wounds) for vancomycin resistance and to intensify efforts to contain

VRE spread, i.e., by strict adherence to handwashing and compliance

with isolation precautions (See Section III-A-4 below). Intensified

fecal screening for VRE may facilitate earlier identification of

colonized patients, leading to more efficient containment of the

microorganism.

III. Prevention and Control of Nosocomial Transmission of VRE

Eradication of VRE from the hospital is most likely to succeed when

VRE infection or colonization is confined to a few patients on a single

ward. Once VRE has become endemic on a ward or has spread to multiple

wards or to the community, eradication becomes extremely difficult and

costly. Aggressive infection control measures and strict compliance by

hospital personnel are required to limit nosocomial spread of VRE.

Control of VRE requires a collaborative institution-wide

multidisciplinary effort. Therefore, involve the hospital's quality

assurance/improvement department at the outset in order to identify

specific problems in hospital operations and patient-care systems and

to design, implement, and evaluate appropriate changes in these

systems.

A. For all hospitals, including those where VRE have been isolated

infrequently or not at all:

1. Notify appropriate hospital staff promptly when VRE is detected.

(See Section II-C-2 above).

2. Make clinical staff aware of the hospital's policies regarding

VRE-infected or colonized patients. Implement the required procedures

as soon as VRE is detected because the slightest delay can lead to

further spread of VRE and complicate control efforts. Clinical staff

play a pivotal role in limiting the spread of VRE in patient-care

areas. Accordingly, continuing education is critical regarding the

appropriate response to the detection of VRE (See Section I above).

3. Establish system(s) for monitoring appropriate process and

outcome measures, such as cumulative incidence or incidence density of

VRE colonization, rate of compliance with VRE isolation precautions and

handwashing, interval between VRE identification in the laboratory and

implementation of isolation precautions on the wards, and the

percentage of previously colonized patients admitted to the ward who

are promptly recognized and placed on isolation precautions. Relay

these data to the clinical, administrative, laboratory, and support

staff as reinforcement to ongoing education and control efforts.\19\

4. Isolation precautions to prevent patient-to-patient transmission

of VRE:

a. Place VRE-infected or colonized patients in single rooms or in

the same room as other patients with VRE.

b. Wear gloves (clean nonsterile gloves are adequate) when entering

the room of a VRE-infected or colonized patient; extensive

environmental contamination with VRE has been noted in some

studies.3,11,20 During the course of caring for a patient, a

change of gloves may be necessary after contact with material that may

contain high concentrations of VRE (e.g., stool).

c. Wear a gown (a clean nonsterile gown is adequate) when entering

the room of a VRE-infected or colonized patient if substantial contact

with the patient or environmental surfaces in the patient's room is

anticipated, or if the patient is incontinent, or has diarrhea, an

ileostomy, a colostomy, or a wound drainage not contained by a

dressing.

d. i. Remove gloves and gown before leaving the patient's room, and

wash hands immediately with an antiseptic soap.4 Hands can be

contaminated via glove leaks21 or during glove removal and bland

soap has been shown to be relatively ineffective in removing VRE from

the hands.\22\

ii. Ensure that after glove and gown removal and handwashing,

clothing and hands do not contact environmental surfaces potentially

contaminated with VRE (e.g., door knob or curtain) in the patient's

room.

5. Dedicate the use of noncritical items, such as stethoscope,

sphygmomanometer, or electronic rectal thermometer, to a single patient

or cohort of patients infected or colonized with VRE.\12\ If such

devices are to be used on other patient(s), adequately clean and

disinfect them first.\23\

6. Culture stools or rectal swabs of roommates of patients newly

found to be infected or colonized with VRE to determine their

colonization status, and apply isolation precautions as necessary.

Perform additional screening of patients on the ward at the discretion

of the infection control staff.

7. Adopt a policy for deciding when patients infected and/or

colonized with VRE can be removed from isolation precautions. The

optimal requirements remain unknown; however, since VRE colonization

may persist indefinitely,\4\ stringent criteria may be appropriate,

e.g., VRE-negative results on at least three consecutive occasions, one

or more weeks apart, for all cultures from multiple body sites

(including stool or rectal swab, perineal area, axilla or umbilicus,

and wound, Foley catheter, and/or colostomy sites if present).

8. Establish a system of highlighting the records of infected or

colonized patients so that they can be recognized and isolated promptly

upon readmission to the hospital because patients with VRE may remain

colonized for long periods following discharge from the hospital.

9. Discharging VRE-infected or colonized patients:

Consult local and state health departments in developing a plan

regarding the discharge of VRE-infected or colonized patients to

nursing homes, other hospitals or home health-care, as part of a larger

strategy for handling patients with resolving infections and patients

colonized with antimicrobial-resistant microorganisms. This plan should

emphasize handwashing and the appropriate use of gloves and gowns when

having direct contact with the above-mentioned patients who are

transferred from hospitals.

B. In hospitals with endemic VRE or continued VRE transmission

despite implementation of measures described in III-A-1 through III-A-

9:

1. Focus control efforts initially on ICUs and other areas where

VRE transmission rate is highest.\4\ Such units may serve as a

reservoir of VRE, from where VRE spreads to other wards when patients

are well enough to be transferred.

2. Cohort staff so that nurses and others providing care to

patients with VRE do not provide care to noncolonized patients during

the same work shift.\4\ Healthcare workers who must provide care to

both groups of patients during the same shift should make every effort

to limit their movement between the two patient groups.

3. Carriers of enterococci on the hospital staff have rarely been

implicated in the transmission of this organism.\11\ Nonetheless, in

conjunction with careful epidemiological studies and upon the direction

of the infection control staff, examine personnel for chronic skin and

nail problems and perform hand and rectal-swab cultures on them as well

as on other personnel providing care to VRE-infected or colonized

patients. Remove VRE-positive personnel epidemiologically linked to VRE

transmission from the care of VRE-negative patients.

4. The results of several enterococcal outbreak investigations

suggest a potential role for the environment in the transmission of

enterococci. In one study, nonoutbreak-related strains of vancomycin-

susceptible enterococci were isolated from cultures of environmental

surfaces in patient rooms before and after terminal room cleaning and

disinfection.CDC unpublished data In institutions experiencing

ongoing VRE transmission, verify that the hospital has adequate

procedures for the routine care, cleaning, and disinfection of

environmental surfaces (e.g., bedrails, charts, carts, doorknobs,

faucet handles, bedside commodes) and that these procedures are being

followed by housekeeping personnel. Some hospitals may elect to perform

focused environmental cultures before and after cleaning of rooms

housing patients with VRE to verify the efficacy of hospital policies

and procedures. All environmental culturing should be approved and

supervised by the infection control program in collaboration with the

clinical laboratory.11,12,20,24

5. Consider sending representative VRE isolates to reference

laboratories for strain typing by pulsed field gel electrophoresis or

other suitable techniques to aid in defining reservoirs and patterns of

transmission.

IV. Prudent Vancomycin Use

Vancomycin use has been reported consistently as a risk factor for

colonization and infection with VRE2,4,12,25 and may increase the

possibility of the emergence of vancomycin-resistant S. aureus (VRSA)

and/or vancomycin-resistant S. epidermidis. Therefore, all hospitals,

even those where VRE has never been detected, should develop a

comprehensive antimicrobial-utilization plan to provide education for

medical staff, oversee surgical prophylaxis, and develop guidelines for

the proper use of vancomycin. Guideline development should be part of

the hospital's quality improvement program and involve participation

from the hospital's pharmacy and therapeutics committee, hospital

epidemiologist, and infection control, infectious diseases, medical,

and surgical staffs. The guidelines should include the following

considerations:

A. Situations in which the use of vancomycin is appropriate or

acceptable:

1. For treatment of serious infections due to beta-lactam resistant

gram-positive microorganisms. Clinicians should be aware that

vancomycin may be less rapidly bactericidal than beta-lactam agents for

beta-lactam susceptible staphylococci.26,27

2. For treatment of infections due to gram-positive microorganisms

in patients with serious allergy to beta-lactam antimicrobials.

3. When antibiotic-associated colitis (AAC) fails to respond to

metronidazole therapy or if AAC is severe and potentially life-

threatening.

4. Prophylaxis, as recommended by the American Heart Association,

for endocarditis following certain procedures in patients at high risk

for endocarditis.28

5. Prophylaxis for surgical procedures involving implantation of

prosthetic materials or devices at institutions with a high rate of

infections due to MRSA or methicillin-resistant S. epidermidis.29

A single dose administered immediately before surgery is sufficient

unless the procedure lasts more than 6 hours, in which case the dose

should be repeated. Prophylaxis should be discontinued after a maximum

of 2 doses.30-32

B. Situations in which the use of vancomycin should be discouraged:

1. Routine surgical prophylaxis.30

2. Empiric antimicrobial therapy for a febrile neutropenic patient,

unless there is strong evidence at the outset that the patient has an

infection due to gram-positive microorganisms (e.g., inflamed exit site

of Hickman catheter), and the prevalence of infections due to beta-

lactam-resistant gram-positive microorganisms (e.g., MRSA) in the

hospital is substantial.2,33-39

3. Treatment in response to a single blood culture positive for

coagulase-negative staphylococcus, if other blood cultures drawn in the

same time frame are negative, i.e., if contamination of the blood

culture is likely. Because contamination of blood cultures with skin

flora, e.g., S. epidermidis, may cause vancomycin to be inappropriately

administered to patients, phlebotomists and other personnel who obtain

blood cultures should be properly trained to minimize microbial

contamination of specimens.

4. Continued empiric use for presumed infections in patients whose

cultures are negative for beta-lactam-resistant gram-positive

microorganisms.37,40

5. Systemic or local (e.g., antibiotic lock) prophylaxis for

infection or colonization of indwelling central or peripheral

intravascular catheters or vascular grafts.41-46

6. Selective decontamination of the digestive tract.

7. Eradication of MRSA colonization.47,48

8. Primary treatment of AAC.49

9. Routine prophylaxis for very low-birth-weight infants.50

10. Routine prophylaxis for patients on continuous ambulatory

peritoneal dialysis.51,52

Further study is required to determine the most effective methods

for influencing the prescribing practices of physicians, although a

variety of techniques may be useful.53-56 In addition, key

parameters of vancomycin use can be tracked through the hospital's

quality assurance/improvement process or as part of the drug-

utilization review of the pharmacy and therapeutics committee and the

medical staff.

V. Detection and Reporting of VRSA

The microbiology laboratory has the primary responsibility for

detecting and reporting the occurrence of VRSA in the hospital.

A. Antimicrobial susceptibility testing: Routinely test all

clinical isolates of S. aureus for susceptibility to vancomycin by

using standard methods.17

B. When VRSA is identified in a clinical specimen:

1. Confirm vancomycin resistance in S. aureus by repeating

antimicrobial susceptibility testing using standard methods.17 It

is advisable to restreak the colony to ensure that the S. aureus

culture is pure. The most common causes of false-positive VRSA report

are susceptibility testing on mixed cultures and misidentification of

VRE, Leukonostoc, S. haemolyticus or Pediococcus as VRSA.57,58

2. Immediately, while performing confirmatory testing, notify the

hospital's infection control personnel, the patient's primary

caregiver, and patient-care personnel on the ward on which the patient

is hospitalized so that the patient can be placed promptly on isolation

precautions adapted from, depending on the site(s) of infection or

colonization,59 those recommended for VRE infection or

colonization. (See Section III-A-4 through III-B-5 above.)

3. Immediately notify the state health department and CDC, and send

the isolate through the state health department to CDC (telephone

number 404-639-1550) for confirmation of vancomycin resistance.

References

1. Centers for Disease Control and Prevention. Nosocomial

enterococci resistant to vancomycin--United States, 1989-1993. MMWR

1993; 42:597-599.

2. Rubin LG, Tucci V, Cercenado E, Eliopoulos G, Isenberg HD.

Vancomycin-resistant Enterococcus faecium in hospitalized children.

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3. Karanfil LV, Murphy M, Josephson A, et al. A cluster of

vancomycin-resistant Enterococcus faecium in an intensive care unit.

Infect Control Hosp Epidemiol 1992; 13:195-200.

4. Handwerger S, Raucher B, Altarac D, et al. Nosocomial

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21. Olsen RJ, Lynch P, Coyle MB, Cummings J, Bokete T, Stamm WE.

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22. Wade JJ, Desai N, Casewell MW. Hygienic hand disinfection

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