Clinical efficacy of continuous infusion of piperacillin compared with intermittent dosing in septic critically ill patients

Since the bactericidal effects of beta-lactam antibiotics are time dependent, the optimum strategy for their administration could be continuous infusion. In this prospective, randomised controlled trial to evaluate the clinical efficacy of continuous infusion therapy, we evaluated the outcomes for 40 septic critically ill patients who received piperacillin either continuously (2 g intravenously (i.v.) over 0.5 h as a loading dose followed by 8 g i.v. daily over 24 It (n = 20)) or as an intermittent infusion (3 g i.v. every 6 It over 0.5 h (n = 20)). Results from our study demonstrated that the clinical efficacy of piperacillin as a continuous infusion is superior to intermittent administration in critically ill patients. Change in APACHE 11 scores from baseline at the end of the second, third and fourth days, respectively, were 4.1, 5.1 and 5.2 for continuous infusion and 2.0, 2.6 and 2.8 for intermittent infusion (P <= 0.04). Considering minimum inhibitory concentrations (MICs) of 16 mu g/mL and 32 mu g/mL, the percentage of time for which piperacillin plasma concentrations were higher than the MIC (%T > MIC) was calculated for each patient in the two groups. For MICs of 16 mu g/mL and 32 mu g/mL, %T > MIC in the continuous infusion group was 100% and 65% of the dosing interval, respectively; in the intermittent infusion group, %T > MIC was only 62% and 39% of the dosing interval. There was a significant relationship between clinical results and laboratory data. It was shown that the superiority of the clinical efficacy of continuous infusion could be related to piperacillin pharmacodynamics. Continuous infusion significantly reduced the severity of illness as demonstrated by APACHE 11 scores during therapy. (c) 2006 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.