Effects of antibiotics on nosocomial epidemiology of vancomycin-resistant enterococci.

Enterococci are gram-positive cocci that are normal inhabitants of the gastrointestinal tract. However, they can also be significant pathogens, causing endocarditis and urinary tract, bloodstream, and wound infection (62). During the last decade, a dramatic increase in the occurrence of vancomycinresistant enterococci (VRE) has been noted in hospitals within the United Kingdom and the United States (16, 87). For instance, a 9-year study from the United Kingdom determined that vancomycin resistance in Enterococcus faecium isolated in blood cultures reached 6.3% in 1993, 20% in 1995, and 24% in 1998 (87). According to the Centers for Disease Control and Prevention, the percentage of enterococcal isolates that were resistant to vancomycin reported by U.S. intensive care units (ICUs) increased from 0.3% in 1989 to 25.2% in 1999 (16). In a recently published international survey (57), the proportion of nosocomial enterococcal isolates in the United States that were resistant to vancomycin (17% in 1999) was much higher than the proportion of vancomycin-resistant enterococcal isolates from patients in the rest of the world (Fig. 1). Since de novo emergence of glycopeptide resistance in enterococci through genetic mutations induced by glycopeptide exposure in an individual patient is unlikely (70), the inexorable increase in the prevalence of VRE in U.S. hospitals during the last decade was accelerated by cross-transmission via the hands of health care workers, contaminated equipment, and environmental surfaces (32, 55, 65, 73). Therefore, the presence of VRE within a hospital environment raises important issues in order to prevent the spread of VRE (65). First, improved hand hygiene practices and reliable cleaning techniques are warranted to decrease the spread of VRE (42). Second, the fact that many seriously ill patients may be asymptomatically colonized requires screening policies for early detection and special isolation precautions for patients carrying VRE (8, 78). Finally, excessive antibiotic usage has been identified as one of the most important modifiable risk factors for VRE occurrence within the hospital setting (70). Although the role of antibiotics in the nosocomial epidemiology of VRE has been extensively studied, many controversies remain. Therefore, we systematically reviewed the effect of antibiotics on the nosocomial epidemiology of VRE. Specifically, we attempted to assess the effect of antibiotic exposure in two different patient populations: (i) VRE-negative patients (the risk of VRE acquisition was assessed in individual patients initially free of VRE) and (ii) patients already colonized with VRE. For the latter group of patients, the following qualities were assessed: (i) likelihood of detection of VRE, (ii) potential for VRE transmission, and (iii) chances of intestinal decolonization of VRE. In addition, we examined intervention studies that tried to modify antibiotic treatment protocols in order to decrease VRE prevalence. Finally, we evaluated potential limitations and biases on the validity of the reported results. A literature search to identify all studies published between January 1980 and February 2001 that examined the role of antibiotic exposure in nosocomial VRE epidemiology was performed using the MEDLINE database and bibliographic review of relevant papers. Articles written in English, French, or German were considered for review. A full text search was performed using the index terms “vancomycin” and “enterococci” in different variations. All articles were considered, including reviews, editorials, book chapters, and clinical studies. We screened studies of hospitalized pediatric and adult patients that evaluated the effect of antibiotic exposure on nosocomial VRE detection, de novo acquisition, transmissibility, and decolonization. All studies reporting the effect of antibiotics on the outcome of interest were considered. Studies were excluded if they did not give any estimates about the effect of antibiotic exposure on nosocomial VRE epidemiology. In addition, we assessed animal or volunteer studies, if they were relevant for the purpose of this review. The decision to include or to exclude an article and the data extraction were accomplished independently by at least two reviewers using a computerized standard form. Disagreement was resolved by consensus. We abstracted the following data for each included study: year of publication, authors, setting, study period, type of study, sample size, exposures and outcomes of interest, inclusion criteria of the study subjects, and pattern of antibiotic exposure. References of all identified publications were entered into a database using reference-managing software (Endnote 4.0; Niles Software, Inc., Berkeley, Calif.). We identified 1,761 potentially relevant articles from the literature search; 120 studies were selected, of which 113 were found to be suitable for this literature review. * Corresponding author. Present address: Infection Control Unit, Department of Internal Medicine, University Hospitals of Geneva, 24, rue Micheli-du-Crest, 1211 Geneva 14, Switzerland. Phone: (41) 22 372 9828. Fax: (41) 22 372 3987. E-mail: [email protected].