Aim: We sought to correlate pharmacokinetic (PK)/pharmacodynamic (PD) predictions of antibacterial efficacy and clinical outcomes in patients with augmented renal clearance (ARC) and 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 -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 . 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 (T> MIC) was estimated. Clinical cure was defined as resolution of signs and symptoms attributable to 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 T>MIC (93.6 [69.9-100] vs. 57.2 [47.6-72.4], < 0.001) and clinical cure (91.7% vs. 74.2%, = 0.039) were significantly higher in cefepime group, whereas mortality (8.3% vs. 22.7%, = 0.1) and infection-related mortality (0% vs. 2%, = 0.54) were similar.
Conclusions: Patients with ARC and pneumonia and/or bacteremia who received extended-infusion cefepime achieved higher T>MIC and clinical cure than those receiving extended infusion piperacillin/tazobactam.
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| http://dx.doi.org/10.4103/IJCIIS.IJCIIS_70_18 | DOI Listing |
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