Beta-lactam antibiotics: is continuous infusion the preferred method of administration?

OBJECTIVE: To examine the pharmacodynamic properties of the beta-lactam class of antibiotics and the rationale for their continuous infusion (CI), and to explore reasons that this mode of administration has not replaced intermittent infusion as the standard of practice. DATA SOURCES: A Medline search of the English-language literature evaluating CI administration of beta-lactam antibiotics was conducted. Bibliographic searches of these articles also were performed. STUDY SELECTION: Because there were few human trials, all available trials were considered for review. A cross section of clinical trials, animal studies, and in vitro studies examining the impact of the route of antibiotic administration was selected for each pharmacodynamic variable addressed. DATA SYNTHESIS: The support for CI as the preferred method of beta-lactam administration comes primarily from in vitro and animal data. Most beta-lactam antibiotics do not demonstrate concentration-dependent killing and have an appreciable postantibiotic effect only against gram-positive cocci. Their efficacy appears to be optimized by maintaining suprainhibitory concentrations throughout the dosing interval. Therefore, CI of beta-lactams could potentially enhance the efficacy of treatment or allow less drug to be used on a daily basis. This has yet to be demonstrated convincingly in human clinical trials. Comparative trials need to continue to explore the impact of the method of administration on patient outcomes such as duration and cost of therapy, as well as morbidity and mortality. CONCLUSIONS: Results of many animal and in vitro studies suggest that CI may be the optimal method of beta-lactam administration. Clinical trials need to further document the impact of the method of beta-lactam administration on the incidence of adverse effects, emergence of bacterial resistance, and patient outcome. Pharmacodynamic studies defining target beta-lactam concentrations, the practicality of CI in patients requiring multiple intravenous fluids and medications, and the pertinence of this issue when beta-lactam antibiotics are used as sole agents or in combination with other antimicrobials require further exploration.