Continuous vs. intermittent vancomycin infusion in critically ill patients: a systematic review and meta-analysis

Vancomycin is a first-line antibiotic for severe gram-positive infections in critically ill patients; however, its narrow therapeutic window and marked interindividual pharmacokinetic variability pose challenges in achieving optimal exposure. This meta-analysis aimed to compare the efficacy and safety of continuous vs. intermittent vancomycin infusion in critically ill patients.

We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science. Randomized controlled trials and observational studies were included. Statistical analyses were performed using Stata 19.0, and pooled risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI) were calculated using random-effects models. Risk of bias was assessed using the Cochrane RoB 2.0 tool for RCTs and the ROBINS-I tool for observational studies; publication bias was evaluated using funnel plots and Egger's test. Sensitivity analyses were performed using the leave-one-out method to assess the robustness of the findings. The certainty of evidence was graded using the GRADE approach.

Twenty-two studies (2,140 patients) were included. Continuous infusion significantly improved serum concentration attainment (RR = 2.23, 95% CI: 1.77-2.80, P < 0.001; I ² = 50.8%) and AUC/MIC attainment (RR = 2.17, 95% CI: 1.60-2.95, P < 0.001; I ² = 39.7%), and significantly reduced the risk of nephrotoxicity (RR = 0.57, 95% CI: 0.46-0.71, P < 0.001; I ² = 0.0%). No significant difference in mortality was observed between the two groups (RR = 1.05, 95% CI: 0.85-1.30, P = 0.629; I ² = 0.0%). Continuous infusion was associated with significantly higher steady-state concentrations (MD = 6.81 mg/L, 95% CI: 3.09-10.54, P < 0.001; I ² = 90.4%) and shorter time to target attainment (MD = -21.64 h, 95% CI: -35.99 to -7.29, P = 0.003; I ² = 84.1%), but no significant difference in AUC/MIC ratio was found (MD = 66.74, 95% CI: -56.20 to 189.67, P = 0.287; I ² = 89.8%). Publication bias was detected for serum concentration attainment (Egger P = 0.001); however, the effect estimate remained significant after trim-and-fill correction (adjusted RR = 1.89, 95% CI: 1.38-2.58). The certainty of evidence was moderate for the primary outcomes and low for the secondary outcomes.

Compared with intermittent infusion, continuous vancomycin infusion significantly improves target concentration attainment and reduces nephrotoxicity without increasing mortality. These findings should be interpreted in the context of potential publication bias and between-study heterogeneity.Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO/view/CRD420261431488), identifier CRD420261431488.