Pharmacokinetic/pharmacodynamic predictions and clinical outcomes of patients with augmented renal clearance and Pseudomonas aeruginosa bacteremia and/or pneumonia treated with extended infusion cefepime versus extended infusion piperacillin/tazobactam

Anthony T Gerlach; Eric Wenzler; Lauren N Hunt; Jose A Bazan; Karri A Bauer

doi:10.4103/IJCIIS.IJCIIS_70_18

Pharmacokinetic/pharmacodynamic predictions and clinical outcomes of patients with augmented renal clearance and Pseudomonas aeruginosa bacteremia and/or pneumonia treated with extended infusion cefepime versus extended infusion piperacillin/tazobactam

Int J Crit Illn Inj Sci. 2019 Jul-Sep;9(3):138-143. doi: 10.4103/IJCIIS.IJCIIS_70_18. Epub 2019 Sep 30.

Authors

Anthony T Gerlach¹, Eric Wenzler², Lauren N Hunt³, Jose A Bazan⁴, Karri A Bauer⁵

Affiliations

¹ Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
² Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
³ ILUM Health Solutions, Kenilworth, NJ, USA.
⁴ Department of Internal Medicine, Division of Infectious Diseases, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
⁵ Merck Research Labs, Kenilworth, NJ, USA.

Abstract

Aim: We sought to correlate pharmacokinetic (PK)/pharmacodynamic (PD) predictions of antibacterial efficacy and clinical outcomes in patients with augmented renal clearance (ARC) and Pseudomonas aeruginosa bacteremia or pneumonia treated with extended infusion cefepime or piperacillin/tazobactam.

Materials and methods: Cefepime (2 g every 8 h) and piperacillin/tazobactam (4.5 g every 8 h) were administered over 4 h after a loading dose infused over 30 min, and minimum inhibitory concentration was determined by E-test. Published population PK evaluations in critically ill patients were used, and PD analyses were conducted using estimated patient-specific PK parameters and known minimum inhibitory concentration values for P. aeruginosa. Concentration-time profiles were generated every 6 min using first-dose drug exposure estimates including a loading infusion, and free concentration above the minimum inhibitory concentration (fT> MIC) was estimated. Clinical cure was defined as resolution of signs and symptoms attributable to P. aeruginosa infection without need for escalation of antimicrobial.

Results: One hundred and two patients were included (36 cefepime and 66 piperacillin/tazobactam). The two groups of patients had similar age, serum creatinine, weight, and creatinine clearance. The majority of patients required intensive care unit care (63.9% vs. 63.6%) and most had pneumonia (61%). The fT>MIC (93.6 [69.9-100] vs. 57.2 [47.6-72.4], P < 0.001) and clinical cure (91.7% vs. 74.2%, P = 0.039) were significantly higher in cefepime group, whereas mortality (8.3% vs. 22.7%, P = 0.1) and infection-related mortality (0% vs. 2%, P = 0.54) were similar.

Conclusions: Patients with ARC and P. aeruginosa pneumonia and/or bacteremia who received extended-infusion cefepime achieved higher fT>MIC and clinical cure than those receiving extended infusion piperacillin/tazobactam.

Keywords: Augmented renal clearance; cefepime; medical outcomes; pharmacodynamics; pharmacokinetics; piperacillin/tazobactam.