We describe an outbreak of vancomycin-resistant Enterococcus faecium (vanA phenotype) bacteremia on the oncology ward of a tertiary care community hospital. In 10 of the 11 cases the patients had leukemia and were neutropenic (median duration of neutropenia, 21 days) at the time of bacteremia. On average, patients received six antibiotic agents for a total of 61 agent-days prior to development of vancomycin-resistant E. faecium bacteremia. The mortality rate was 73%. Molecular typing of 22 isolates revealed that the majority (83%) represented a common strain, indicating nosocomial spread. When the 11 cases were compared to 22 matched control patients, gastrointestinal colonization with vancomycin-resistant E. faecium (odds ratio [denominator, 0] infinity, P = .005) and the use of antimicrobial agents with significant activity against anaerobes (metronidazole, clindamycin, and imipenem; odds ratio infinity, P = .02) were found to be risk factors for the development of vancomycin-resistant E. faecium bacteremia. Since no proven therapy for such infection exists, there is an urgent need to identify effective measures to prevent and control the development of vancomycin-resistant E. faecium bacteremia.

Previous studies have shown that bacteremia due to vancomycin-resistant Enterococcus species (VRE) is associated with mortality of 17%-100%, but comorbid conditions may have confounded the estimates. We designed a historical cohort study to determine the mortality attributable to VRE bacteremia. Twenty-seven patients with VRE bacteremia were identified as cases. Within 7 days of the onset of bacteremia, severe sepsis developed in 12 patients (44%) and septic shock developed in 10 (37%). Case patients were closely matched to control patients without VRE bacteremia (1:1) by time of hospitalization, duration of exposure, underlying disease, age, gender, and surgical procedure. The mortality was 67% among cases and 30% among matched controls (P = 0.1). Thus, the mortality attributable to VRE bacteremia was 37% (95% confidence interval [CI], 10%-64%) and the risk ratio for death was 2.3 [CI, 1.2-4.1). We conclude that VRE bacteremia is associated with high rates of severe sepsis and septic shock. The attributable mortality approaches 40%, and patients who have VRE bacteremia are twice as likely to die than closely matched controls.

Combination antimicrobial agent therapy has been advocated for treatment of gram-negative bacteremia, including that caused by KlebsielUa spp. We performed a prospective, observational, 10-hospital collaborative study to evaluate the efficacy of antibiotic combination therapy versus that of monotherapy for 230 consecutive patients with KiebsieUla bacteremia. The species involved were K. pneumoniae (82%), K. oxytoca (15%), and K. ozaenae (0.4%). Of the bacteremias, 26% were polymicrobial in nature. A total of 53% of cases were nosocomial infections. The most common portals were the urinary tract (28%), biliary tract (12%), lung (10%b), and abdomen (9%k). Some 49 and 51% of the patients had received monotherapy and antibiotic combination therapy (beta-lactam plus aminoglycoside), respectively; 14-day mortalities in the two groups were 20 and 18%, respectively. However, for the subgroup of patients who experienced hypotension within 72 h prior to or on the day of the positive blood culture, those patients who received combination therapy experienced significantly lower mortality (24%) than did those who received monotherapy (50%k). We conclude that monotherapy with an antibiotic that is active in vitro against KiebsieUla (beta-lactam or aminoglycoside) is sufficient therapy for less severely ill patients (immunocompetent, urinary tract portal, mentally alert, normal vital signs). On the other hand, for severel ill patients who experience hypotension, antibiotic combination therapy with a beta-lactam and an aminoglycoside agent is preferred.Klebsiella spp. are the second most frequent cause of gram-negative bacteremia (3,5,12,14). Combination therapy with a beta-lactam and an aminoglycoside has been advocated for treatment of Klebsiella bacteremia because of its notable mortality (1,11,15).Most studies of bacteremia have focused on Klebsiella spp. not as a single entity but, rather, have included it in the category of gram-negative bacteremias. This is problematic, given the inherent differences in antibiotic susceptibility and virulence among the aerobic gram-negative rods. Young (15) has also pointed out that failure to stratify patients by underlying disease category in most studies of therapy for gram-negative bacteremia has resulted in invalid comparisons of antibiotic efficacy.We performed a prospective, observational, multicenter collaborative study to evaluate the efficacy of antibiotic combination therapy versus monotherapy on the outcome of Klebsiella infections. We made a concerted effort to address those areas of weakness that have characterized previous studies, including a prospective rather than retrospective study design, adequate sample size for statistical evaluation, assessment for severity of illness, and requirement for bacteremia as an eligibility criterion. Furthermore, given the large sample size of 230 patients, analysis by subgroups including underlying disease was feasible. MATERIALS AND METHODSStudy design. From 1986 to 1987, 230 consecutive patients from whose blood Klebsiella spp. were ...