Better outcomes through continuous infusion of time-dependent antibiotics to critically ill patients?

Increasing interest is being directed toward possible benefits associated with continuous infusion of time-dependent antibiotics such as beta-lactams and vancomycin to critically ill patients. The background, emerging evidence and practical considerations associated with continuous infusions are discussed.

One large retrospective cohort study has found clinical outcome benefits of administering a beta-lactam antibiotic by extended infusion compared with bolus administration. This complements a smaller randomized controlled trial comparing continuous infusion and intermittent bolus administration. For vancomycin, clinical outcome benefits have only been shown in a ventilator-associated pneumonia cohort of critically ill patients. No clinical outcome studies have been conducted for other time-dependent antibiotics.

Continuous infusion of vancomycin and beta-lactam antibiotics enables faster and more consistent attainment of therapeutic levels compared with intermittent bolus dosing. Although the clinical benefits have not been conclusively shown at this time, compelling pharmacokinetic/pharmacodynamic support for continuous infusion nevertheless exists. Given that critically ill patients may develop very large volumes of distribution as well as supranormal drug clearances, individualized therapy through the use of therapeutic drug monitoring is required. A definitive determination of the relative clinical efficacy of intermittent bolus and continuous administration of beta-lactams or vancomycin will only be achieved after a large-scale multicenter randomized controlled trial has been performed.