Prolonged versus intermittent vancomycin infusion in critically ill patients with sepsis: A systematic review and meta-analysis

Abstract

Abstract Background Vancomycin is often used empirically as a first-line drug for methicillin-resistant Staphylococcus aureus therapy in patients with sepsis. This review aimed to clarify the clinical efficacy and safety of prolonged vancomycin infusion compared to intermittent infusion in adult patients with acute severe infection. Methods Potentially eligible trials were identified by searching the MEDLINE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi (ICHUSHI) online databases. We selected randomized controlled trials and observational studies in which the clinical outcomes of adult patients with sepsis or septic shock were compared between prolonged and intermittent vancomycin infusion strategies. Two investigators independently screened the search results and extracted data. The primary outcome was all-cause mortality at the maximum follow-up. Secondary outcomes included the attainment of the target plasma concentration, clinical cure, and adverse events, such as nephrotoxicity. Results Sixteen studies were identified for the analysis of baseline characteristics. A total of 214 patients from three randomized trials and 1999 patients from 13 observational studies were included. Mortality rates of patients receiving prolonged infusion and patients receiving intermittent infusion were similar (pooled risk ratios, 1.05; 95% confidence intervals, 0.63–1.74; P = 0.85 in randomized controlled trials and pooled risk ratios, 1.07; 95% confidence intervals, 0.74–1.55; P = 0.71 in observational studies). Patients treated with prolonged infusion had a significantly higher attainment of the target plasma concentration compared with patients receiving intermittent infusion (pooled risk ratios, 5.62; 95% confidence intervals, 2.09–15.07; P < 0.001 in randomized controlled trials and pooled risk ratios, 2.27; 95% confidence intervals, 1.393.71; P = 0.001 in observational studies). No significant difference was detected in the other outcomes. Conclusions Our findings revealed that, compared with intermittent administration, prolonged infusion of vancomycin may be advantageous for controlling blood vancomycin levels.