A-1906. Examination of the Current Renal Dose Adjustment for Piperacillin/Tazobactam (PT)
Session: Poster Session: Human Pharmacokinetics/Dynamics
Monday, October 27, 2008: 12:00 AM
Room: Hall C
Background: The current recommendation is to dose adjust PT 4.5 G IV Q6H to PT 3.375 G IV Q6H for CrCls 20-40 ml/min. The impact of this dose adjustment regimen on probability of target attainment (PTA) and degree of accumulation is currently unknown. Methods: Data for 105 subjects were analyzed using BigNPAG. Plasma clearance (CL) was proportional to estimated CrCl plus an intercept (CL= CLslope x CrCl + CLintercept). Monte Carlo simulation (ADAPT II) was used to estimate the PTA of f50% T>MIC for PT 4.5 G IV Q6H (0.5 hr inf) and PT 3.375 G IV Q6H (0.5 hr inf) at CrCl of 20 ml/min and 40 ml/min. For both regimens, the degree of accumulation was determined by taking the ratio of the distribution of AUC24SS when CrCL was 20 and 40ml/min relative to the AUC24SS distribution for 4.5 G IV Q6H when the CrCl was fixed at 100 ml/min. Results: PTA profiles were similar between regimens (fig). However, PTA sharply fell for both regimens at MICs > 16mg/L. The mean (SD) accumulation ratio for 3.375 G IV Q6H at CrCl at 20 and 40 ml/min were 1.86 (0.56) and 1.33 (0.22). In contrast, the mean (SD) accumulation ratio for 4.5 G IV Q6h at CrCl of 20 and 40 ml/min were 2.48 (0.75) and 1.77(0.30).
Conclusions: Current recommended renal dose adjustments for PT provide a similar PTA without significant accumulation. However, the PTA profile of the renal dose adjustment regimen does not support a susceptibility breakpoint of > 16 mg/L.
George Drusano, MD, Ordway Research Inst, Albany, NY, Marc Scheetz, PharmD, MSc, Midwestern Univ, Downers Grove, IL, Nimish Patel, PharmD, Albany College of Pharmacy and Health Sciences, Albany, NY, Thomas Lodise, PharmD, Albany College of Pharmacy, Albany, NY and  M. H. Scheetz,
Theradoc Inc Role(s): Grant Investigator, Received: Grant Recipient.
Cubist Role(s): Grant Investigator, Received: Educational Grant.