Antibiotic selection factors and description of a hospital-based outpatient antibiotic therapy program in the USA

Abstract

A variety of pharmacodynamic, pharmacokinetic and drug stability factors can influence the choice of drug, the dosing regimen and the method of drug administration for outpatient parenteral antibiotic therapy (OPAT). Beta-lactam antibiotics exhibit little if any concentration-dependent killing and produce short-term or no persistent effects with most bacterial pathogens. Optimal dosing regimens for these agents should provide serum levels that continually exceed the minimal inhibitory concentration (MIC) of the pathogen. Beta-lactam agents with long half-lives (greater than 2 hours) can provide these levels with intermittent dosing once or twice daily. Beta-lactam agents with shorter half-lives can be administered by programmable pumps or by continuous infusion providing the drug is sufficiently stable to degradation in solution. Imipenem and ampicillin are examples of drugs with short half-lives that are unstable in solution and must be dosed intermittently. Intramuscular administration slows absorption and can also prolong the length of time during which serum levels exceed the MIC of infecting bacteria. Aminoglycosides and fluoroquinolones, on the other hand, exhibit concentration-dependent killing and produce prolonged persistent effects. Optimal dosage regimens of these drugs should maximize serum levels. Once-daily dosing regimens for the aminoglycosides meet this goal and also appear to reduce drug-induced nephrotoxicity. Application of these principles to drug selection and administration in a hospital-based OPAT program has provided efficacious therapy and a low incidence of adverse reactions in an elderly population distributed over a wide geographic area.