January 2, 1996


Vancomycin Use in an Era of VRE

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. From 1989 though 1993, the percentage of nosocomial enterococcal infections reported to the Centers for Disease Control and Prevention (CDC) National Nosocomial Infections Surveillance (NNIS) System that were due to vancomycin-resistant enterococci (VRE) increased from 0.3% to 7.9%. The increase was due mainly to the rise from 0.4% to 13.6% in Intensive Care Unit (ICU) patients, but an increase in VRE infections also was noted in non-ICU patients. The occurrence of VRE in NNIS hospitals was associated with larger hospital size (3,200 beds) and university affiliation. Other hospitals also have reported increased endemic rates and clusters of VRE infection and colonization. The actual increase in the incidence of VRE in U.S. hospitals may be larger than reported, because the fully automated methods used in many clinical laboratories cannot consistently detect vancomycin-resistance.

Certain patient populations have been found to be at increased risk for VRE infection or colonization. These include seriously 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 major surgical procedures, and those who have had prolonged hospital stay or received multi-antimicrobial and/or vancomycin therapy. 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. 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 personnel, contaminated environmental surfaces and patient-care equipment.

The epidemiology of VRE has not been elucidated in Canada. There have been sporadic reports of VRE in at least 10 Canadian institutions since 1993. TTH has just experienced the first significant outbreak of VRE in Canada, with one infection and 38 colonized patients. Many of the patient risk factors identified in U.S. centers were found in our patient population as well. Vancomycin usage at TTH has increased 32% (from 13,000 to 18,000 gms) over the last 4 years and the setting for a potentially serious problem with VRE exists at TTH.

In addition to the existing problem with VRE, the potential emergence of vancomycin-resistance in clinical isolates of Staphylococcus aureus or Staphylococcus epidermidis is a serious public health concern. The gene carrying this resistance confers high-level resistance to vancomycin, and can be transferred in vitro from enterococci to a variety of gram-positive microorganisms, including S. aureus.

In response to the increase in vancomycin resistance in enterococci, and given the presence of VRE at TTH, the Antibiotic Subcommittee and the Pharmacy and Therapeutics Committee recommend the following:


  1. For suspect or documented C. difficle colitis, oral vancomycin will be automatically substituted with oral metronidazole; oral vancomycin use will be restricted to treatment failures with metronidazole (no resolution after 5 days of therapy).

  2. Adoption of the CDC's Hospital Infection Control Practices Advisory Committee (HICPAC) recommendations for preventing the spread of VRE, specifically as they relate to the antibiotic control measures which are outlined below:


  • A. Situations in Which the Use of Vancomycin Should Be Discouraged

    1. Routine surgical prophylaxis other than in a patient with life-threatening allergy (Type I hypersensitivity reaction) to beta-lactam antibiotics.
    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 and the prevalence of infections due to methicillin-resistant Staphylococcus aureus (MRSA) in the hospital is substantial.
    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, contamination of the blood culture is likely. Because contamination of blood cultures with skin flora, e.g., S. epidermidis, may cause vancomycin to be administered to patients inappropriately, phlebotomists and other personnel who obtain blood cultures should always attempt 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.
    5. Systemic or local (e.g., antibiotic lock) prophylaxis for infection or colonization of indwelling central or peripheral intravascular catheters.
    6. Selective decontamination of the digestive tract.
    7. Eradication of MRSA colonization.
    8. Primary treatment of antibiotic-associated colitis (AAC) (TTH has adopted an automatic substitution policy of metronidazole instead of vancomycin in this setting).
    9. Routine prophylaxis for very low birth-weight infants.
    10. Routine prophylaxis for patients on continuous ambulatory peritoneal dialysis or haemodialysis.
    11. Treatment (chosen for dosing convenience) of infections due to beta-lactam-sensitive gram-positive microorganisms in patients with renal failure
    12. Use of vancomycin solution for topical application or irrigation.


    B. 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.
    2. For treatment of infections due to gram-positive microorganisms in patients with serious allergy to beta-lactam antimicrobials.
    3. When 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.
    5. Prophylaxis for major surgical procedures involving implantation of prosthetic materials or devices, e.g., cardiac and vascular procedures and total hip replacement, at institutions with a high rate of infections due to MRSA or methicillin-resistant S. epidermidis. 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 two doses.

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