Nosocomial Enterococci Resistant to Vancomycin -- United States, 1989-1993

As part of continual surveillance for antibiotic resistance among pathogens associated with nosocomial infections, a recent analysis of data reported to CDC's National Nosocomial Infections Surveillance (NNIS) system demonstrated a 20-fold increase in the percentage of enterococci associated with nosocomial infections that are resistant to vancomycin from January 1, 1989, through March 31, 1993. Many of these strains are resistant to all available antimicrobial agents. This report summarizes that analysis.

The NNIS system began in 1970 when selected U.S. hospitals routinely reported nosocomial infection surveillance data for aggregation into a national data base; it is the only source of national data on the epidemiology of nosocomial infections in the United States. Isolates of Enterococcus sp. from nosocomial infections reported to the NNIS system from January 1, 1989, through March 31, 1993, were examined. Up to four pathogens could be reported for each episode of nosocomial infection. Multiple isolates of the same species from the same patient were not reported. Information on site of isolation (e.g., respiratory tract or urinary tract), place of acquisition of infection (intensive-care unit (ICU) or non-ICU), medical school affiliation of hospital (teaching or nonteaching), hospital size, and the hospital's susceptibility testing method was obtained for each infection and/or isolate.

Of 16,571 nosocomial Enterococcus isolates, 10,961 (66.2%) were tested for vancomycin susceptibility; 278 (2.5%) were resistant. The percentage of nosocomial enterococci resistant to vancomycin increased from 0.3% in 1989 to 7.9% in 1993 (p less than 0.0001, chi-square test). Among patients in ICUs with nosocomial infections, the percentage of enterococcal isolates resistant to vancomycin increased from 0.4% in 1989 to 13.6% in 1993 (p less than 0.0001) (Figure 1). Vancomycin resistance varied by site of infection: gastrointestinal (e.g., intraabdominal abscess), skin and soft tissue, and bloodstream sites had the highest percentage of resistant nosocomial enterococci (7.8%, 4.1%, and 3.8%, respectively).

Of the 10,961 nosocomial enterococcal isolates tested for vancomycin susceptibility and reported to the NNIS system, 1881 were from primary bloodstream infections; 323 (17.2%) patients died. Of the patients with primary bloodstream infection, mortality was significantly higher in those with vancomycin-resistant isolates compared with those with vancomycin-susceptible isolates (26 (36.6%) of 71 versus 297 (16.4%) of 1810; p less than 0.0001, chi-square test). Insufficient data on comorbidity were obtained to determine the relation of the bloodstream infection to death in these patients.

Vancomycin-resistant nosocomial enterococci have been reported from nine of 33 states with NNIS hospitals; the highest percentages were from NNIS hospitals in New York, Pennsylvania, and Maryland (8.9%, 5.6%, and 3.6%, respectively). Vancomycin resistance also varied by teaching affiliation of hospital: 14 (0.6%) of 2154 nosocomial enterococci at nonteaching hospitals were resistant versus 264 (3.0%) of 8807 at teaching hospitals (p less than 0.0001, chi-square test). The percentage of vancomycin resistance varied also by number of beds in the hospital: none of 384 nosocomial enterococci at hospitals with fewer than 200 beds, 105 (1.8%) of 5780 nosocomial enterococci at hospitals with 200-500 beds, and 173 (3.6%) of 4797 at hospitals with more than 500 beds. Vancomycin resistance did not vary substantially by method of susceptibility testing.

Since 1989, of 32 vancomycin-resistant nosocomial enterococci isolates from the NNIS system examined at CDC for confirmation of resistance, 20 demonstrated high-level vancomycin and teicoplanin resistance (the VanA phenotype) where the minimum inhibitory concentration (MIC) was greater than 128 ug/mL for vancomycin and greater than 8 ug/mL for teicoplanin; 12 isolates that were teicoplanin susceptible demonstrated moderate vancomycin resistance with a MIC 16-64 ug/mL (the VanB phenotype).

Reported by: National Nosocomial Infections Surveillance system participating hospitals. Hospital Infections Program, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: Vancomycin resistance represents a serious challenge for physicians treating patients with bacterial infections, particularly because many hospital-acquired E. faecium strains also are resistant to (beta)-lactam and aminoglycoside anti biotics (1). Treatment options for patients with nosocomial infections associated with vancomycin-resistant enterococci are limited, often to unproven combinations of antimicrobials or experimental compounds (2). The data presented in this report suggest that vancomycin resistance among nosocomial enterococci is increasing dramatically, especially in ICUs, and that both the VanA and VanB phenotypes are present among these resistant nosocomial pathogens.

Because information on the myriad of risk factors that influence mortality (e.g., smoking status, age, and comorbidity) are not collected, NNIS data cannot be used to estimate the increased risk for death from a particular site of nosocomial infection. The observed differences in mortality for patients with vancomycin-resistant compared with vancomycin-susceptible nosocomial enterococcal bloodstream infections may be explained in part by differences in these risk factors.

Enterococci may also serve as a reservoir for resistance genes for other gram-positive organisms, including Staphylococcus aureus. Laboratory evidence suggests that transfer of the vanA gene from enterococci to S. aureus can occur and generate a vancomycin-resistant S. aureus (3). However, clinical strains of S. aureus that are vancomycin resistant have not been reported to CDC. Vancomycin resistance in coagulase-negative staphylococci has been reported rarely (4); none has been reported through the NNIS system.

Detection of vancomycin resistance using in vitro susceptibility testing methods remains difficult (5). In particular, isolates with the VanB phenotype often are not detected with automated methods. The NNIS data may represent both underreporting of resistance and a bias in favor of detecting only the VanA phenotype. The National Committee for Clinical Laboratory Standards has approved changes in the disk diffusion testing methodology to increase the accuracy of this test (6) and is assessing a vancomycin resistance agar screen test using 6 ug/mL of vancomycin in brain-heart infusion agar. These changes should enhance the ability of microbiology laboratories to detect resistant enterococci.

Control measures for vancomycin-resistant enterococci include more consistent application of infection-control precautions and control of indiscriminate vancomycin use (7,8). Vancomycin use is a risk factor for colonization with vancomycin-resistant enterococci (9); however, the transmission of the resistant organism can be controlled and eradicated in a hospital by intensive infection-control efforts.

References

1. Moellering RC Jr. The Garrod Lecture -- the enterococcus: a classic example of the impact of antimicrobial resistance on therapeutic options. J Antimicrob Chemother 1991:28:1-12.

2. Fraimow HS, Venuti E. Inconsistent bactericidal activity of triple-combination therapy with vancomycin, ampicillin, and gentamicin against vancomycin-resistant, highly ampicillin-resistant Enterococcus faecium. Antimicrob Agents Chemother 1992;36:1563-6.

3. Noble WC, Virani Z, Cree R. Cotransfer of vancomycin and other resistance genes from Enterococcus faecalis NCTC12201 to Staphylococcus aureus. FEMS Microbiology Letters 1992;93:195-8.

4. Veach LA, Pfaller MA, Barrett M, Koontz FP, Wenzel RP. Vancomycin resistance in Staphylococcus haemolyticus causing colonization and bloodstream infection. J Clin Microbiol 1990; 28:2064-8.

5. Swenson JM, Hill BC, Thornsberry C. Problems with disk diffusion test for detection of vancomycin resistance in enterococci. J Clin Microbiol 1989;27:2140-2.

6. Swenson JM, Ferraro MJ, Sahm DF, Charache P, Tenover F, National Committee for Clinical Laboratory Standards. New vancomycin disk diffusion breakpoints for enterococci. J Clin Microbiol 1992;30:2525-8.

7. Weinstein RA. Epidemiology and control of nosocomial infections in adult intensive care units. Am J Med 1991;91(suppl):179S-84S.

8. Rubin LG, Tucci V, Cercenado E, Eliopoulos G, Isenberg HD. Vancomycin-resistant Enterococcus faecium in hospitalized children. Infect Control Hosp Epidemiol 1992;13:700-5.

9. 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.

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