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

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 (f T> 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 f T>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 f T>MIC and clinical cure than those receiving extended infusion piperacillin/tazobactam.