Critical Care Network
Beta-lactam antibiotics, including penicillin, carbapenems, and cephalosporins, exhibit time-dependent bacterial eradication. Prolonged infusions are thought to enhance the duration of effective bactericidal antibiotic exposure, decreasing the emergence of drug resistance due to reduced bacterial regrowth between doses – which may lead to cost savings by reducing drug acquisition costs and shortening hospital stays (Lodise TP Jr, et al. Clin Infect Dis.).
The best evidence for these benefits comes from observational studies and meta-analyses. The Defining Antibiotic Levels in Intensive Care Unit Patients (DALI) study emphasized the correlation between achieving target concentrations of beta-lactam antibiotics in critically ill patients and positive clinical outcomes for bloodstream infections but not for lung or intra-abdominal infections (Roberts JA, et al. Clin Infect Dis.). A meta-analysis of 29 studies suggested that prolonged infusion of piperacillin-tazobactam was associated with a mortality benefit compared with intermittent infusions, but prolonged infusions of cephalosporins or carbapenems resulted in comparable outcomes without mortality benefit (Teo J, et al. Int J Antimicrob Agents. ).
MERCY was a multinational, randomized controlled trial investigating the efficacy of continuous vs intermittent administration of meropenem in critically ill patients with sepsis. The primary outcome, a composite of mortality and emergence of resistant bacteria at day 28, showed no significant difference between continuous and intermittent administration (47% vs. 49%). Secondary outcomes and adverse events also did not display significant differences, suggesting that continuous meropenem did not improve outcomes compared with intermittent administration (Monti G, et al. JAMA.).
MERCY adds to the existing body of evidence suggesting that prolonged and intermittent infusion strategies for meropenem are at least equivalent in efficacy. Therefore, the strategy chosen can depend on other individualized factors.
The views expressed are those of the authors and do not reflect the official policy or position of the U.S. Navy, Department of Defense, or the US Government.
Meredith L. Olsen, MD, Section Member-at-Large
Casey Cable, MD, FCCP, Section Member-at-Large
Kathryn Pendleton, MD, FCCP, Section Vice-Chair