Outcomes with Extended-Infusion Piperacillin/Tazobactam in Pediatrics

Background: In 2011, standard piperacillin/tazobactam (PT) dosing in children at our hospital was changed from a traditional infusion regimen of 84.4 mg/kg IV every 6 hours, infused over 30 minutes to an extended infusion piperacillin/ tazobactam (EIPT) regimen of 112.5 mg/kg IV every 8 hours, infused over 4 hours in an effort to optimize antibiotic dosing and clinical outcomes. Improved mortality with EIPT has been demonstrated in some adult studies, but outcomes data in children are lacking. The objective of the study was to compare 21-day clinical cure and safety outcomes in pediatric patients receiving traditional PT vs. EIPT.

Methods: Electronic medical records of patients aged one month through 17 years with a documented gram-negative infection who received traditional PT or EIPT for at least 48 hours between April 2010 and March 2012 were reviewed. Patients were excluded if they received more than one dose of an additional antimicrobial with gram-negative activity, received multiple PT dosage regimens, were inadequately treated for gram-positive or fungal infection, were cared for in the neonatal intensive care unit, or received any type of renal replacement therapy. Patients were categorized as having clinical cure if at 21 days following PT initiation they were afebrile, had complete symptomatic resolution, had white blood cell count normalization, and had negative follow-up cultures, when available.

Results: One thousand and four patient encounters were screened, of which 85 patients (35 in traditional PT and 50 in EIPT) were enrolled. Median [IQR] age did not differ between the traditional PT and EIPT groups (36 [17 – 132] months vs. 84 [24 – 132], respectively; p = 0.220).  There were no differences in other baseline demographics between the groups.  Between traditional and EIPT recipients, there were similar clinical cure rates (86% vs. 74%, respectively; p = 0.193) and 30-day readmission rates (34% vs. 32%, respectively; p = 0.825).  There was no occurrence of 30-day mortality in either group.  Serum creatinine increased greater than 50% over baseline values in 5.7% and 10% of patients receiving traditional PT and EIPT, respectively (p = 0.695).

Conclusion: In this cohort of pediatric patients EIPT was equally as effective as traditional PT.  Clinical implications for standard EIPT dosing in children warrant further study.