Meta-analysis on safety of standard vs prolonged infusion of beta-lactams

Abstract

AbstractBackgroundEfficacy for prolonged infusion beta-lactam dosing schemes has been previously described, but there has been less focus on the safety of standard vs prolonged infusion protocols of beta-lactams. This study explored differences in adverse drug reactions (ADRs) reported for beta-lactams between each of these infusion protocols.MethodsA systematic review of MEDLINE literature databases via PubMed was conducted and references were compiled. Articles were compiled and assessed with specific inclusion/exclusion criteria. We included randomized and nonrandomized, prospective, and retrospective cohort studies that reported adverse effects due to either standard (30-60 mins) or prolonged (≥3 hours) infusions of beta-lactam infusions. Total ADRs between strategies were analyzed by infusion methodology. The most consistently reported ADRs were subject to meta-analysis across studies.Results13 studies met inclusion/exclusion criteria with data for 4184 patients. There was insufficient data to systematically analyze neurotoxicity or cytopenias. Eight studies reported on nephrotoxicity outcomes with no significant difference in event rates between standard (n=440/2117, 20.8%) vs prolonged infusion (n=264/1284, 20.6%) of beta-lactams (OR=1.09, 95% CI [0.91, 1.30]). Six studies reported on rates of diarrhea with no significant difference in event rates between standard (n=21/359, 5.8%) vs prolonged infusion (n=25/330, 7.6%) of beta-lactams (OR=1.33, 95% CI [0.71,2.47).ConclusionProlonged and standard infusion schemes for beta-lactams demonstrated adverse effects at similar rates for both infusion schemes. Future research should focus on improved standardization of adverse effect definitions and a priori aim to study neurotoxicity and cytopenias. Consistent recording of ADRs and standardized definitions of these reactions will be paramount to further study of this subject.