Continuous versus Intermittent Intravenous Administration of Antibacterials with Time-Dependent Action

Abstract

We performed a systematic review of randomised clinical trials to evaluate the comparative pharmacokinetic and pharmacodynamic properties of the continuous versus intermittent mode of intravenous administration of various antibacterials. Data were identified from PubMed (January 1950 to January 2005), Current Contents, the Cochrane central register of controlled trials, and references from relevant articles and reviews. Seventeen randomised clinical trials comparing continuous with intermittent intravenous administration of the same antibacterial regimen and examining the pharmacokinetic and pharmacodynamic properties were included in this systematic review. We reviewed data regarding the clinical setting, number of participants, antibacterial agents and dosages used, as well as maximum serum concentration (Cmax), trough serum concentration (Cmin), steady-state or plateau serum concentration (Css), area under the concentration-time curve (AUC), time above the minimum inhibitory concentration (MIC) [T>MIC], AUC: MIC, elimination rate constant, elimination half-life, volume of distribution and systematic clearance. The mean Cmax of the intermittently administered antibacterials was higher compared with Css achieved by the continuous infusion of the same antibacterial in all eligible studies (Cmax was on average 5.5 times higher than Css, range 1.9-11.2). Css was on average 5.8 times higher than the Cmin of the intermittently administered antibacterials (range 1.2-15.6). In three of six studies the length of time that the drug concentration was above the MIC of the responsible pathogens was longer in patients receiving the antibacterials continuously. In conclusion, the reviewed data suggest that the continuous intravenous infusion of antibacterials with time-dependent bacterial killing seems to be superior than the intermittent intravenous administration, from a pharmacodynamic point of view, at least when treating bacteria with high MIC values for the studied antibacterials.