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.
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.
['Gerlach|Anthony T|AT|', 'Wenzler|Eric|E|', 'Hunt|Lauren N|LN|', 'Bazan|Jose A|JA|', 'Bauer|Karri A|KA|']
pharmacokinetics pharmacodynamics Augmented renal clearance cefepime piperacillin/tazobactam medical outcomes