Comparison of extended versus intermittent infusion of antipseudomonal beta-lactams for the treatment of critically ill patients with respiratory infections: A systematic review and meta-analysis

OBJECTIVES: Alternative dosing strategies for β-lactams - the most common antibiotics used to treat critically ill patients with respiratory tract infections - have been recommended to maximize the duration of exposure and reduce drug resistance. The objective of this study was to evaluate whether extended infusion of antipseudomonal β-lactams improves mortality and clinical efficacy. METHODS: Two independent authors identified eligible trials by searching the PubMed, Cochrane Library, Scopus, and ICHUSHI databases, in both English and Japanese, up to June 2019. Data were extracted from both randomized controlled and observational trials comparing extended infusion (≥3h) with intermittent infusion in critically ill patients. The primary outcome was all-cause mortality. Risk differences (RD) and 95% confidential intervals (CI) were calculated using a random-effects model and subgroup analyses were performed. Sensitivity and heterogeneity were also evaluated. RESULTS: Nine studies involving 1508 participants were included in the meta-analysis. Mortality was lower for extended infusion than for intermittent infusion (RD -0.10; 95% CI -0.15 to -0.04). However, no significant between-group differences in clinical success, length of ICU stay, length of hospital stay, and antibiotic duration were observed. CONCLUSIONS: Extended infusions of β-lactams were associated with reduced mortality rates but not with clinical success.