Continuous infusion of β-lactam antibiotics in severe infections: a review of its role

Continuous infusion of β-lactam antibiotics has been widely promoted to optimise their time-dependent activity. Increasing evidence is emerging suggesting potential benefits in patient populations with altered pathophysiology, such as seriously ill patients. From a pharmacokinetic viewpoint, much information supports higher trough concentrations of β-lactam antibiotics when administered by continuous infusion. This advantage of continuous infusion translates into a superior ability to achieve pharmacodynamic targets, particularly when the minimum inhibitory concentration (MIC) of the pathogen is ≥4 mg/L. One drawback of continuous infusion may be limited physicochemical stability. This issue exists particularly for carbapenem antibiotics whereby prolonged infusions (i.e. >3 h) can be used to improve the time above the MIC compared with conventional bolus dosing. Few studies have examined clinical outcomes of bolus and continuous dosing of β-lactam antibiotics in seriously ill patients. No statistically significant differences have been shown for: mortality; time to normalisation of leukocytosis or pyrexia; or duration of mechanical ventilation, intensive care unit stay or hospital stay. Some evidence suggests improved clinical cure and resolution of illness with continuous infusion in seriously ill patients. Pharmacoeconomic advantages of continuous infusion of β-lactam antibiotics are well characterised. Available data suggest that seriously ill patients with severe infections requiring significant antibiotic courses (≥4 days) may be the subgroup that will achieve better outcomes with continuous infusion.