In Critically Ill, Extended Infusion of Meropenem Correlated with Faster Progression to Death

SAN DIEGO, CA—In critically ill adult patients, extended infusion of meropenem correlates with a faster progression to death vs. intermittent infusion of the drug.  And extended infusion of piperacillin/tazobactam showed a trend toward faster progression to death vs. intermittent infusion of the agent, according to an evaluation of clinical and economic outcomes presented at IDWeek 2012.

Study author Lacy Ternes, PharmD, from the University of Minnesota Medical Center, Fairview, Minneapolis, noted an increase in antibiotic resistance and deficiency of new antibiotic therapies encourages the optimization of pharmacokinetic and pharmacodynamic properties of existing antibiotics. Monte Carlo simulations have shown advantageous bactericidal effectiveness with extended infusions of meropenem and piperacillin/tazobactam.

A single-center, retrospective chart review assessed the impact of extended vs. intermittent infusions of meropenem and piperacillin/tazobactam. Data were collected from patients admitted from January 1 through December 31, 2010 for intermittent infusion and from November 1, 2011 through April 1, 2012 for extended infusions. Patients receiving ≥48 hours of meropenem (500mg every 6 hours) or piperacillin/tazobactam (3.375g every 8 hours) were included.

The primary outcome was in-hospital all-cause mortality. Secondary outcomes included hospital and ICU length of stay and time to normalization of white blood cell count and temperature.

A total of 100 patients received meropenem (n=36 extended infusion; n=64 intermittent infusion). Patients who received extended infusion experienced a faster progression to death (HR=4.3, 95% CI, 1.8–10.1, P=0.0002) and a longer hospital length of stay (median for extended infusions=27 days; median for intermittent infusion=17 days, P=0.02) and ICU length of stay (median for extended infusion=13 days; median for intermittent infusion=4 days, P=0.03).

A total of 148 patients received piperacillin/tazobactam (n=48 extended infusion; n=100 intermittent infusion). Patients who received extended infusion showed a trend toward faster progression to death (HR=1.5, 95% CI, 0.6–3.6, P=0.3927), although this was not statistically significant. For all secondary outcomes, no statistically significant differences were seen. A 13.2% reduction in average cost/patient/day was seen for patients who received extended infusion.

“Despite theoretical benefit of extended infusion beta-lactam antibiotics, this study suggests an increased risk of mortality in the extended infusion group,” Dr. Ternes concluded. “Although there was a potential cost savings associated with extended infusion piperacillin/tazobactam, this cannot be divorced from measures of effectiveness. Further research is warranted; specifically, prospective evaluation of extended infusion beta-lactams in clinical outcomes through a randomized-controlled trial.”