C.D.C. -

22 september 1995

Recommendations for Preventing the Spread of Vancomycin Resistance
Recommendations of the Hospital Infection Control Practices Advisory Committee (HICPAC).



Since 1989, a rapid increase in the incidence of infection and colonization with vancomycin-resistant enterococci (VRE) has been reported by U.S. hospi-tals. This increase poses important problems, including a) the lack of available antimicrobial therapy for VRE infections, because most VRE are also resistant to drugs previously used to treat such infections (e.g., aminoglycosides and am-picillin), and b) the possibility that the vancomycin-resistant genes present in VRE can be transferred to other gram-positive microorganisms (e.g., Staphylococcus aureus ).

An increased risk for VRE infection and colonization has been associated with previous vancomycin and/or multiantimicrobial therapy, severe underlying dis-ease or immunosuppression, and intraabdominal surgery. Because enterococci can be found in the normal gastrointestinal and female genital tracts, most en-terococcal infections have been attributed to endogenous sources within the individual patient. However, recent reports of outbreaks and endemic infections caused by enterococci, including VRE, have indicated that patient-to-patient transmission of the microorganisms can occur either through direct contact or through indirect contact via a) the hands of personnel or b) contaminated pa-tient-care equipment or environmental surfaces.

This report presents recommendations of the Hospital Infection Control Practices Advisory Committee for preventing and controlling the spread of vancomycin resistance, with a special focus on VRE. Preventing and controlling the spread of vancomycin resistance will require coordinated, concerted efforts from all involved hospital departments and can be achieved only if each of the following elements is addressed: a) prudent vancomycin use by clinicians, b) education of hospital staff regarding the problem of vancomycin resistance, c) early detection and prompt reporting of vancomycin resistance in enterococci and other gram-positive microorganisms by the hospital microbiology labora-tory, and d) immediate implementation of appropriate infection-control meas-ures to prevent person-to-person transmission of VRE.


>From 1989 through 1993, the percentage of nosocomial enterococcal infections re-ported to CDC„200 beds) and university affiliation ( 1 ). Other hospitals also have reported increased endemic rates and clusters of VRE infection and coloni-zation ( 2 to 8 ). The actual increase in the incidence of VRE in U.S. hospitals might be greater than reported because the fully automated methods used in many clinical laboratories cannot consistently detect vancomycin resistance, especially moderate vancomycin resistance (as manifested in the VanB phenotype) ( 9 to11 ). Vancomycin resistance in enterococci has coincided with the increasing incidence of high-level enterococcal resistance to penicillin and aminoglycosides, thus present-ing a challenge for physicians who treat patients who have infections caused by these microorganisms ( 1,4 ). Treatment options are often limited to combining antimicro-bials or experimental compounds that have unproven efficacy ( 12 to14 ).

The epidemiology of VRE has not been clarified; however, certain patient popula-tions are at increased risk for VRE infection or colonization. These populations include critically ill patients or those with severe underlying disease or immunosuppression (e.g., patients in ICUs or in oncology or transplant wards); persons who have had an intraabdominal or cardio-thoracic surgical procedure or an indwelling urinary or cen-tral venous catheter; and persons who have had a prolonged hospital stay or received multiantimicrobial and/or vancomycin therapy ( 2 - 8 ). 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


Each hospital -;through collaboration of its quality-improvement and infection-control programs; pharmacy and therapeutics committee; microbiology laboratory; 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. The following elements should be addressed in the plan.


Vancomycin use has been reported consistently as a risk factor for infection and colonization with VRE ( 2,4,7,8,17 ) and may increase the possibility of the emergence of vancomycin-resistant S. aureus (VRSA) and/or vancomycin-resistant S. epider-midis (VRSE). Therefore, all hospitals and other health-care delivery services, even those at which VRE have never been detected, should

a) develop a comprehensive, antimicrobial-utilization plan to provide education for their medical staff (including medical students who rotate their training in different departments of the health-care facility),

b) oversee surgical prophylaxis, and

c) develop guidelines for the proper use of vancomycin (as applicable to the institution). Guideline development should be part of the hospital

## Situations in which the use of vancomycin is appropriate or acceptable: ## Situations in which the use of vancomycin should be discouraged:


Continuing education programs for hospital staff (including attending and consult-ing physicians, medical residents, and students[59]; pharmacy, nursing, and laboratory personnel[59]; and other direct patient-care providers) should include information con-cerning 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 an aggressive approach and high performance standards for hospital personnel, special awareness and educational sessions might be indicated.

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 Identification of Enterococci Presumptively identify colonies on primary isolation plates as enterococci by using colonial morphology, a Gram stain, and a pyrrolidonyl arylamidase (PYR) test.

Al-though identifying enterococci to the species level can help predict certain resistance patterns (e.g., Enterococcus faecium is more resistant to penicillin than is Enterococ-cus faecalis ) and may help determine the epidemiologic relatedness of enterococcal isolates, such identification is not routinely necessary if antimicrobial susceptibility testing is performed.

However, under special circumstances or as laboratory re-sources permit, biochemical tests can be used to differentiate between various enterococcal species. Although most commercially available identification systems adequately differentiate E. faecalis from other species of enterococci, additional tests for motility and pigment production are required to distinguish Enterococcus galli-narum (motile and nonpigmented) and Enterococcus casseliflavus (motile and pigmented) from E. faecium (nonmotile and nonpigmented).

Tests for Antimicrobial Susceptibility Determine vancomycin resistance and high-level resistance to penicillin (or am-picillin) and aminoglycosides ( 62 ) for enterococci isolated from blood, sterile body sites (with the possible exception of urine), and other sites as clinically indicated.

Laboratories routinely may test wound and urine isolates for resistance to vancomy-cin and penicillin or ampicillin if resources permit (see Screening Procedures for Detecting VRE in Hospitals Where VRE Have Not Been Detected).

When VRE Are Isolated From a Clinical Specimen

Confirm vancomycin resistance by repeating antimicrobial susceptibility testing using any of the recommended methods (see Tests for Antimicrobial Susceptibility), particularly if VRE isolates are unusual in the hospital, OR streak 1 mL of standard in-oculum (0.5 McFarland) from an isolated colony of enterococci onto brain heart infusion agar containing 6 mg/mL of vancomycin, incubate the inoculated plate for 24 hours at 35 C (95 F), and consider any growth indicative of vancomycin resistance ( 62,63,65 ). Immediately, while performing confirmatory susceptibility tests, notify the patient

Hospital screening
Where VRE Have Not Been Detected

In some hospital microbiology laboratories, antimicrobial susceptibility testing of enterococcal isolates from urine or nonsterile body sites (e.g., wounds) is not per-formed routinely; thus, identification of nosocomial VRE colonization and infection in hospitalized patients may be delayed. Therefore, in hospitals where VRE have not yet been detected, implementing special measures can promote earlier detection of VRE.

Antimicrobial susceptibility survey.

Perform periodic susceptibility testing on an epidemiologic sample of enterococcal isolates recovered from all types of clinical specimens, especially from high-risk patients (e.g., those in an ICU or in an oncology or transplant ward). The optimal frequency of testing and number of isolates to be tested will vary among hospitals, depending on the patient population and number of cultures performed at the hospital.

Hospitals that process large numbers of culture specimens need to test only a fraction (e.g., 10%) of enterococcal isolates every 1-2 months, whereas hospitals processing fewer specimens might need to test all en-terococcal isolates during the survey period. The hospital epidemiologist can help design a suitable sampling strategy. Culture survey of stools or rectal swabs. In tertiary medical centers and other hos-pitals that have many critically ill patients (e.g., ICU, oncology, and transplant patients) at high risk for VRE infection or colonization, periodic culture surveys of stools or rec-tal swabs of such patients can detect the presence of VRE.

Because most patients colonized with VRE have intestinal colonization with this organism, fecal screening of patients is recommended even though VRE infections have not been identified clini-cally ( 2,4,16 ). 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 health-care facilities in a hospital


Preventing and Controlling Nosocomial Transmission of VRE

Eradicating VRE from hospitals is most likely to succeed when VRE infection or colonization is confined to a few patients on a single ward. After VRE have become endemic on a ward or have spread to multiple wards or to the community, eradication becomes difficult and costly. Aggressive infection-control measures and strict compli-ance by hospital personnel are required to limit nosocomial spread of VRE. Control of VRE requires a collaborative, institution-wide, multidisciplinary effort. Therefore, the hospital

Preventing and Controlling VRE Transmission in All Hospitals

The following measures should be implemented by all hospitals, including those in which VRE have been isolated infrequently or not at all, to prevent and control trans-mission of VRE.

Hospitals With Endemic VRE or Continued VRE Transmission

The following measures should be taken to prevent and control transmission of VRE in hospitals that have endemic VRE or continued VRE transmission despite imple-mentation of measures described in the preceding section (see Preventing and Controlling VRE Transmission in All Hospitals).


The microbiology laboratory has the primary responsibility for detecting and re-porting the occurrence of VRSA or VRSE in the hospital. All clinical isolates of S. aureus and S. epidermidis should be tested routinely, using standard methods, for susceptibility to vancomycin ( 62 ).

If VRSA or VRSE is identified in a clinical specimen, confirm vancomycin resistance by repeating antimicrobial susceptibility testing using standard methods ( 62 ). Restreak the colony to ensure that the culture is pure.

The most common causes of false-positive VRSA reports are susceptibility testing on mixed cultures and misidentifying VRE, Leuconostoc, S. haemolyticus, or Pediococ-cus as VRSA ( 81,82 ). Immediately (i.e., while performing confirmatory testing) notify the hospital


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