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.


OBJECTIVE
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.
Carmeli
Y
Y
Divisions of Infectious Diseases, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Mass, USA. ycarmeli@mailexcite.com
Samore
M H
MH
Huskins
C
C
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015982:Bias; D016022:Case-Control Studies; D015986:Confounding Factors, Epidemiologic; D003428:Cross Infection / Q000382:microbiology*; D016983:Enterococcus / Q000187:drug effects*; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology*; D006801:Humans; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011643:Publishing; D012107:Research Design; D012306:Risk; D014640:Vancomycin / Q000009:adverse effects* / Q000627:therapeutic use; D020713:Vancomycin Resistance
D000900:Anti-Bacterial Agents; D014640:Vancomycin