Optimal dosing of antibiotics in critically ill patients using continuous/extended infusions: a systematic review and meta-analysis.
Crit Care. 2013 Nov 29;17(6):R279
Authors: Chant C, Leung A, Friedrich JO
INTRODUCTION: The aim of this study was to determine whether using pharmacodynamic-based dosing of antimicrobials such as extended/continuous infusions in critically ill patients is associated with improved outcomes as compared to traditional dosing methods METHODS: We searched Medline, HealthStar, EMBASE, Cochrane Clinical Trial Registry, and CINAHL from inception to September 2013 without language restrictions for studies comparing the use of extended/continuous infusions to traditional dosing. Two authors independently selected studies, extracted data on methodology and outcomes, and performed quality assessment. Meta-analyses were performed using random-effects models.
RESULTS: Of 1319 citations, 13 randomized controlled trials (RCTs) (n = 782 patients) and 13 cohort studies (n = 2117 patients) met the inclusion criteria. Compared to traditional non-pharmacodynamic-based dosing, RCTs of continuous/extended infusions significantly reduced clinical failure rates (relative risk (RR) 0.68, 95% confidence interval (CI) 0.49 to 0.94, P = 0.02) and intensive care unit length of stay (mean difference -1.5, 95% CI -2.8 to -0.2 days, P = 0.02), but not mortality (RR 0.87, 95% CI 0.64 to 1.19, P = 0.38). There was no significant between-trial heterogeneity for these analyses (I2 = 0%). Reduced mortality rates almost achieved statistical significance when the results of all included studies (RCTs and cohort studies) were pooled (RR 0.83, 95% CI 0.69 to 1.00, P = 0.054).
CONCLUSIONS: Pooled results from small RCTs suggest reduced clinical failure rates and intensive care unit length-of-stay when using continuous/extended infusions of antibiotics in critically ill patients. Reduced mortality rates almost achieved statistical significance when the results of RCTs were combined with cohort studies. These results support the conduct of adequately powered RCTs to better define the utility of continuous/extended infusions in the era of antibiotic resistance.
PMID: 24289230 [PubMed - as supplied by publisher]