A pilot study on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving piperacillin/tazobactam
Page hits: 2710, File downloaded: 1091
Download fileDownload this file
Open in browserOpen this file in your browser
AuthorsJirina Martinkova, Manu L.N.G. Malbrain, Eduard Havel, Petr Safranek, Jan Bezouska, Milan Kaska
In critically ill patients, multi-trauma and intensive therapy can influence the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics with time-dependent bacterial killing. Consequently, PK/PD targets (%fT>MIC) - crucial for antimicrobial effects -may not be attained.
Two patients admitted to the surgical ICU of the University Hospital in Hradec Králove for multiple-trauma were given piperacillin/tazobactam by 1-hour IV infusion 4/0.5 g every 8h. PK variables: total and renal clearance (CLtot, CLR), volume of distribution (Vd), and elimination half-life (T1/2) were calculated, followed by glomerular filtration rate (MDRD) and cumulative fluid balance (CFB-total fluid volume based on 24-h registered fluid intake minus output). The PK/PD target attainment (100%fT>MIC) was defined as free (f) piperacillin plasma concentrations that remain, during the entire dosing interval (T), above the minimum inhibitory concentration (100%fT>MIC) within days 4-8 (when CFB culminates and disappears). Piperacillin concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and corrected for unbound fraction (22%).
CFB culminated over days 2-5 reaching 15-30 L and was associated with a large Vd (29-42 L). While MDRD in patient 1 was low (0.3-0.4 mL s?¹ 1.7 m?²), that of patient 2 was increasing (> 3.1 mL s?¹ 1.7 m?²), which was associated with augmented CLR. In patient 2, the fT reached only 62, 52, and 44% on days 4, 6, and 8, respectively. In patient 1, the %fT was much higher, attaining values four to fivefold greater than that targeted.
Critically ill patients are at risk of drug under- or overdosing without dose up-titration with regard to covariate effects and individual drug pharmacokinetics.