Vancomycin-Resistant and Vancomycin-Susceptible Enterococcal Bacteremia: Comparison of Clinical Features and Outcomes

1127 Vancomycin-Resistant and Vancomycin-Susceptible Enterococcal Bacteremia: Comparison of Clinical Features and Outcomes Gregory M. Lucas, Noah Lechtzin, D. Wonder Puryear, Linda L. Yau, Charles W. Flexner, and Richard D. Moore From the Department of Medicine, The Johns Hopkins University, Baltimore, Maryland Vancomycin-resistant Enterococcus (VRE) is a major nosocomial pathogen. We collected clinical and laboratory data on 93 hospitalized adults with VRE bacteremia and 101 adults with vancomycinsusceptible enterococcal (VSE) bacteremia. Risk factors for VRE bacteremia included central venous catheterization, hyperalimentation, and prolonged hospitalization prior to the initial blood culture. VRE-infected patients were less likely to have undergone recent surgery or have polymicrobial bacteremia, suggesting a pathogenesis distinct from traditional VSE bacteremia. Prior exposure to metronidazole was the only significant pharmacologic risk factor for VRE bacteremia. Animal studies suggest metronidazole potentiates enterococcal overgrowth in the gastrointestinal tract and translocation into the bloodstream. An increasing APACHE II score was the major risk factor for death in a multivariate analysis, with VRE status being of only borderline significance. Received 14 October 1997; revised 7 January 1998. Presented in part at the Infectious Diseases Society of America meeting (poster session) on 15 September 1997 in San Francisco. Current addresses: Dr. D. Wonder Puryear, Kirklin Clinic, University of Alabama at Birmingham, Birmingham, Alabama 35233; Dr. Linda L. Yau, East Baltimore Medical Center, 1000 East Eager Street, Baltimore, Maryland 21202. Reprints: Dr. Richard D. Moore, 1830 Building, Room 8059, The Johns Hopkins Hospital, Baltimore, Maryland 21212. Correspondence: Dr. Gregory M. Lucas, Carnegie 346, The Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, Maryland 21287. Clinical Infectious Diseases 1998;26:1127–33 q 1998 by The University of Chicago. All rights reserved. 1058–4838/98/2605–0019$03.00 / 9c4c$$my59 04-10-98 01:30:34 even greater concern is the emergence of vancomycin resistance in more virulent gram-positive organisms. Previous studies have indicated that VRE bacteremia is associated with extensive comorbid pathology, prolonged hospitalizations, heavy exposure to antimicrobial agents, and high crude mortality rates [14 – 18]. The pathogenesis of VRE bacteremia is incompletely described, and the role of VRE itself in producing excess mortality is controversial [14, 18]. We conducted a case-control study of the clinical characteristics, antibiotic usage, microbiological factors, and clinical endpoints for patients with VRE and vancomycin-susceptible enterococcal (VSE) bacteremia in an academic medical center. Our study is the largest reported series of VRE bacteremia cases from a single institution. Methods A database of the Department of Microbiology of The Johns Hopkins Hospital (Baltimore) was culled for all inpatient enterococcal blood isolates from August 1991 until September 1996. One-hundred thirty-seven patients with VRE-positive blood cultures were identified. Patients with VSE bacteremia were selected such that the distribution of initial culture dates was the same as for the VRE-infected patients. Specifically, for each VRE-infected patient, a VSE-infected patient was selected from the database whose date of onset of initial bacteremia was most proximal to the initial culture date of the VREinfected counterpart. Patients’ medical charts were then reviewed in a systematic manner for demographic, clinical, and microbiological data points. A structured data collection form was used to abstract data in eight categories from patients’ records. Only records from which five or more of these categories were able to be completed were included in subsequent analysis. Data regarding exposure to antimicrobials and other pharmaceuticals prior to the initial episode of bacteremia were obtained cida UC: CID Vancomycin-resistant Enterococcus (VRE) emerged in the 1990s as a major nosocomial pathogen. The first descriptions of plasmid-mediated resistance to vancomycin among enterococci appeared in 1988 [1, 2]. Resistant organisms established endemicity at many centers, particularly large, tertiary-care teaching hospitals [3 – 8]. From 1989 to 1993 the percentage of nosocomial enterococcal pathogens that were resistant to vancomycin increased 20-fold according to the National Nosocomial Infections Surveillance system [9]. In 1993, nearly 14% of enterococci isolated in intensive care units were resistant to vancomycin [9]. At one center, point-prevalence studies revealed that 20% of inpatients were colonized with VRE [8]. Enterococci, particularly Enterococcus faecium, have intrinsic resistance to many antibiotics, notably penicillinase-resistant penicillins, cephalosporins, and clindamycin. During the 1970s and 1980s, isolates increasingly emerged with acquired, high-level resistance to ampicillin and aminoglycosides [10 – 12]. The addition of vancomycin resistance to this profile resulted in a pathogen that is untreatable with most available antibiotics. Efforts to prevent colonization with universal precautions and restricted vancomycin utilization at centers where VRE is endemic have been largely unsuccessful [8, 13]. Of 1128 Lucas et al. / 9c4c$$my59 04-10-98 01:30:34 Table 1. Clinical features of patients with VRE or VSE bacteremia. Percentage of patients with bacteremia due to Variable Demographic data Age (y)* Male sex White ethnicity In ICU at time of bacteremia Hospitalization days prior to culture* Clinical characteristics APACHE II score* Diabetes mellitus Malignancy Organ transplant recipient HIV-positive Recent surgery† Assisted ventilation Central venous catheter Receiving hyperalimentation Urinary catheter Fecal incontinence Decubitus ulcers Treatments and outcomes Antibiotic therapy changed in response to initial bacteremia Vascular catheter removed Hospitalization days after initial culture* Length of hospitalization* Any ICU stay Days in ICU per patient* Crude mortality VSE (n Å 101) VRE (n Å 93) P value 60.4 { 16.3 53 49 39 56.1 { 17.5 56 70 38 .125 .732 .003 .888 16.8 { 23.2 24.4 { 24.1 õ.001 17.8 { 9.1 23 32 4 11 62 33 77 36 60 39 5 20.1 { 8.9 19 31 8 8 41 37 88 53 61 47 10 .044 .536 .940 .275 .420 .004 .570 .031 .014 .647 .305 .202 79 46 56 47 21.8 { 20.8 38.6 { 31.2 61 12.5 { 19.0 27 24.7 { 39.9 49.1 { 48.3 70 17.1 { 20.7 45 õ.001 .879 .682 .050 .166 .028 .007 NOTE. APACHE Å acute physiology and chronic health evaluation; ICU Å intensive care unit; VRE and VSE Å vancomycin-resistant and vancomycinsusceptible Enterococcus. * Continuous variables are expressed as means ( {SD). † Surgery within 2 weeks prior to onset of bacteremia or during prior hospitalization. dates and administration dates generated potential treatment bias. Statistical analysis of the data was performed with use of Epi-In (...truncated)