The association between antecedent vancomycin treatment and hospital- acquired vancomycin-resistant enterococci: A meta-analysis

Background: The association between vancomycin hydrochloride treatment and vancomycin-resistant enterococci (VRE) has been investigated in numerous studies with variable results. Objectives: To conduct a meta-analysis to estimate the magnitude of the association between vancomycin treatment and individual risk of VRE and to identify study characteristics that accounted for heterogeneity in study results. Methods: Studies were identified using MEDLINE with index terms 'Enterococcus,' 'Enterococcus faecalis,' or 'Enterococcus faecium' and 'vancomycin,' 'drug resistance,' 'drug resistance, microbial,' or 'drug resistance, multiple or risk factors.' Reports from conferences and reference lists of recent reviews were used A total of 420 published reports and 98 conference reports were reviewed; 20 studies described in 15 published reports were included in the analysis. We recorded study period, hospital setting, case and control definitions, length of hospital stay, method of adjustment for differences in length of stay, and data on treatment with vancomycin. The odds ratio (OR) of vancomycin treatment provided the measure of association analyzed. A random-effects model was used to estimate the pooled OR. Results: When results from all 20 studies were combined, the pooled OR was 4.5 (95% confidence interval, 3.0- 6.9), but the test for heterogeneity was highly significant (P<.001). The 5 studies that used patients with vancomycin-susceptible enterococci as controls found a stronger association (pooled OR, 10.7; 95% confidence interval, 4.8-23.8) than the 15 studies that used controls who had no VRE isolated (pooled OR, 2.7; 95% confidence interval, 2.0-3.8). After restricting the analysis to the latter studies only, no heterogeneity was evident in the unadjusted study results. Patients with VRE had stayed in the hospital much longer than control patients. Studies that adjusted for this difference found only a small and nonsignificant association between vancomycin treatment and VRE (pooled OR, 1.4; 95% confidence interval, 0.74- 2.60). We also detected publication bias, favoring report of studies that found a large measure of association. Conclusions: The reported strong association between vancomycin treatment and hospital-acquired VRE results from the selection of the reference group, confounding by duration of hospitalization, and publication bias. Studies that accounted for these factors found only a small and nonsignificant association.