Systematic review and meta‐analysis of vancomycin therapeutic level for treatment of vancomycin‐sensitive enterococcal infections

Abstract Aims Evidence on the optimal targets of vancomycin for treating other Gram‐positive infections apart from methicillin‐resistant Staphylococcus aureus (MRSA) is lacking. This review aims to identify the recommended vancomycin therapeutic level for favourable clinical outcomes among patients infected with vancomycin‐sensitive enterococcal infections. Methods Analytical studies describing the vancomycin levels of vancomycin‐sensitive enterococcal infections among adult population were searched. The primary outcome was 30‐day all‐cause mortality, and the secondary outcomes were clinical failure and nephrotoxicity. Study characteristics were extracted and pooled using random‐effects meta‐analysis. The study quality was assessed using the Joanna Briggs Institute critical appraisal tool. Results A total of nine retrospective cohorts studies involving 1013 patients with vancomycin‐sensitive enterococci were included. The meta‐analysis found that high area under the curve to minimum inhibitory concentration ratio (AUC/MIC) of vancomycin ≥ 389 mg*h/L significantly lowered the 30‐day mortality (odds ratio [OR], 0.44, 95% confidence interval [CI], 0.26–0.75). Analysis of the target AUC/MIC showed that high vancomycin AUC/MIC (≥ 389–400 mg*h/L) significantly reduced clinical failure rate (OR 0.59, 95% CI 0.37–0.94). The mortality and treatment failure rates did not differ significantly between those with high or low trough levels. Higher vancomycin AUC/MIC and trough levels were significantly associated with increased nephrotoxicity (OR 3.11, 95% CI 1.65–5.89; OR 2.95, 95% CI 1.60–5.44, respectively). Conclusions The use of a higher vancomycin AUC/MIC concentration can be effective to reduce 30‐day mortality and clinical failure but this needs to take into consideration the risk of nephrotoxicity. Well‐conducted prospective studies are warranted due to the scarcity of evidence.