VRE Kills!
Abstract & Commentary
Synopsis: VRE bacteremia is an independent predictor of death, and appropriate antibiotic therapy is associated with improved survival.
Source: Vergis E, et al. Determinants of vancomycin resistance and mortality rates in enterococcal bacteremia. A prospective multicenter study. Ann Intern Med. 2001;135:484-492.
Vergis and colleagues at 4 U.S. academic medical centers and one community hospital performed a prospective observational study of patients with enterococcal bacteremia in order to determine whether vancomycin resistance is an independent predictor of death as well as whether outcome is affected by appropriate antibiotic therapy.
Sixty percent of the 398 bloodstream isolates were Enterococcus faecalis and 37% E faecium; 35% of the 398 were vancomycin resistant (VRE; MIC > 32 µg/mL), while 2% were intermediate (MIC 816 µg/mL). Eight percent of E faecalis and 80% of E faecium were vancomycin resistant. Eighty-seven percent of E faecium were resistant to ampicillin, 60% had high-level gentamicin resistance, and 22% had reduced susceptibility to quinupristin/dalfopristin; linezolid was not tested in this study that ended in March 1977.
Thirty-eight percent of the 147 patients with VRE bacteremia and 49% of those with susceptible enterococcal bacteremia had more than one organism recovered in blood culture (P = 0.007). Infection at an abdominal site other than the biliary tract was 4 times more common (20% vs 4%) in the patients with VRE bacteremia compared to those with susceptible isolates. Vascular catheters were the most common site of infection in the former group and the second most common site in the latter. Endocarditis was present in 3% of patients in each group.
Multivariate analysis found that the independent risk factors for VRE bacteremia were receipt of vancomycin within the previous 14 days, receipt of glucocorticosteroids within the previous 14 days, and the severity of illness (APACHE II score). Risk factors for death within 14 days were the presence of an underlying hematologic malignancy, vancomycin resistance (odds ratio [OR], 2.10; 95% confidence interval [CI], 1.14-3.88; P = 0.02), and severity of illness.
Bacteriological failure was more common with VRE infection (12/16 vs 4/16; P = 0.001). In a multivariate analysis restricted to 208 patients with monomicrobial VRE bacteremia, APACHE II score was a risk factor for 14-day mortality, while receipt of appropriate antibiotic therapy within 48 hours of of the initial positive blood culture was protective (OR, 0.21; 95% CI, 0.06-0.80; P = 0.02).
Comment by Stan Deresinski, MD, FACP
This study addresses a central question related to VRE, the answer to which had previously remained uncertain: Does VRE matter? Previous studies have resulted in varying answers. For instance, a case control study identified VRE bacteremia as being associated with greater all-cause mortality than was bacteremia with vancomycin-susceptible strains.1 However, other studies have found that, although patients with VRE bacteremia do, indeed, have greater overall mortality, vancomycin resistance is not an independent predictor of mortality and is more likely simply a marker of the severity of comorbity.2
The paper under review—the senior author of which is Bob Muder, an editor and important contributor to Infectious Disease Alert—authoritatively answers the question of the relevance of VRE bacteremia in the affirmative. They have demonstrated that VRE bacteremia and lack of effective antibiotic therapy active against VRE in patients with bacteremia are each independent risk factors for mortality.
These observations have important implications. First, vigorous attempts to prevent patient acquisition of VRE are warranted. This means implementation of effective infection control practices to limit the spread of VRE and control of use of relevant antibiotics that predispose to colonization with VRE, especially vancomycin. It also means that strong consideration be given to screening of high-risk patients for colonization with VRE.
The results of this study also demonstrate that a low threshold for administration of antibiotics likely to be active against VRE must be maintained in the appropriate settings. Thus, in institutions in which VRE are prevalent, the presence of organisms morphologically compatible with enterococci observed on Gram staining of blood culture should trigger the use of an antibiotic likely to be effective against VRE, at least until definitive microbiological data are available. This is likely to be a policy unpopular with those responsible for the pharmacy budget, since the antibiotic most reliably active against VRE is linezolid—according to the Medical Letter, in 2000 the average wholesale cost of 600 mg vial was $72 and that of a 600 mg tablet was $53.3
Dr. Deresinski, Clinical Professor of Medicine, Stanford; Director, AIDS Community Research Consortium; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor of Infectious Disease Alert.
References
1. Bhavnani SM, et al. Diagn Microbiol Infect Dis. 2000; 36:145-158.
2. Lautenbach E, et al. Infect Control Hosp Epidemiol. 1999;20:318-323.
3. Medical Letter 2000;42:45-46.
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