Extended versus bolus infusion of meropenem and piperacillin: a pharmacokinetic analysis

Background. Extended infusion of beta-lactam antibiotics has been advocated as a method for optimizing antibiotic exposure in critically ill patients. The objective of this study was to compare the pharmacokinetics/pharmacodynamics of extended infusion versus bolus infusion of piperacillin and meropenem in critically ill patients with normal renal function. Methods. A prospective study of 3 hours extended infusion of meropenem and piperacillin in critically ill patients without renal dysfunction. Results from the extended infusion cohort were compared to previously published bolus infusion data in critically ill patients. Results. Twenty extended infusion patients (15 piperacillin, 5 meropenem) were compared with 13 bolus infusion patients (8 piperacillin, 5 meropenem). The demographic and clinical characteristics between both groups were not statistically different. Significant pharmacokinetic differences were observed in median (interquartile range) C-max for both meropenem (extended infusion 17 [12.6-21.9] vs. bolus 85.2 [66.7-140.3]; P=0.01) and piperacillin (extended infusion 76.2 [57.7-92.6] vs. bolus 240.2 [168.5-275.4]; P=0.001). Considerable pharmacokinetic variability existed in each group for both drugs. Compared to bolus infusion, f Gamma(>MIC) using extended infusion was higher for both drugs: 96% (IQR 71-100%) compared to 77% (IQR 41-93%) for piperacillin (P=0.05) and 82% (IQR 63-89%) compared to 51% (IQR 48-63%) for meropenem (P=0.095); assuming a MIC of 16 mg/L and 2 mg/L respectively. Conclusion. This study confirms that extended infusion in critically ill patients result in advantageous pharmacokinetic profiles by increasing the f Gamma(>MIC) for piperacillin and meropenem. In a significant subpopulation of critically ill patients with normal renal function, a 100% f Gamma(>MIC) target is not reached, even with 3-hour extended infusions.

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