Prolonged β-lactam infusion for Gram-negative Infections.

The emergence of multidrug-resistant organisms coupled with an alarming scarcity of new antibiotic classes in the pipelines of the pharmaceutical industry has forced the healthcare community to optimize the therapeutic potential of currently available antibiotics. The primary determinant of -lactam efficacy is the duration of time in which the nonprotein-bound drug concentration (fT) exceeds the minimum inhibitory concentration (MIC) of the organism (fT MIC). With intermittent dosing, -lactams attain a high peak concentration, but short half-lives can lead to precipitous drops in their serum drug levels. Optimizing fT MIC is particularly difficult for organisms with elevated MICs. Prolonging the infusion time provides more consistent serum levels and maximizes fT MIC (Fig. 1). Prolonging the infusion of -lactams consists of either extended infusion or continuous infusion. Extended infusions are defined as intermittent infusions lasting 3 hours, whereas continuous infusion involves infusion over a 24-hour period at a fixed rate. To date, all clinical outcome studies of prolonged -lactam infusions for Gram-negative infections have been conducted in adults. In this review, we outline the available clinical data on prolonged -lactam administration and propose infusion strategies that could be considered in pediatric patients.