Are standard doses of piperacillin sufficient for critically ill patients with augmented creatinine clearance?
Crit Care. 2015 Jan 30;19(1):28
Authors: Udy AA, Lipman J, Jarrett P, Klein K, Wallis SC, Patel K, Kirkpatrick C, Kruger PS, Paterson DL, Roberts MS, Roberts JA
IntroductionThe aim of this study was to explore the impact of augmented creatinine clearance, and differing minimum inhibitory concentrations (MIC), on piperacillin pharmacokinetic/pharmacodynamic (PK/PD) target attainment (time above MIC - fT>MIC), in critically ill septic patients receiving intermittent dosing.MethodsCritically ill patients with sepsis receiving piperacillin-tazobactam 4.5 g intravenously (IV) by intermittent infusion every 6-hours for presumed or confirmed nosocomial infection, without significant renal impairment (defined by a plasma creatinine concentration >171 ¿mol/L or the need for renal replacement therapy), were eligible for enrolment. Over a single dosing interval, blood samples were drawn to determine unbound plasma piperacillin concentrations. Renal function was assessed by a measured creatinine clearance (CLCR, mL/min). A population PK model was constructed, and the probability of target attainment (PTA) for 50% and 100% fT>MIC calculated for varying MIC and CLCR values.ResultsIn total, 48 patients provided data. Increasing CLCR was associated with lower trough plasma piperacillin concentrations (P <0.01), such that with an MIC of 16 mg/L, 100% fT>MIC would only be achieved in one-third (n¿=¿16) of patients. Mean piperacillin clearance was approximately 1.5 fold higher than in healthy volunteers, and correlated with CLCR (r¿=¿0.58, P <0.01). A reduced PTA for all MIC values, when targeting either 50% or 100% fT>MIC, was noted with increasing CLCR measures.ConclusionsStandard intermittent piperacillin-tazobactam dosing is unlikely to achieve optimal piperacillin exposures in a significant proportion of critically ill patients with sepsis, due to elevated drug clearance. These data suggest CLCR can be employed as a useful tool to determine whether piperacillin PK/PD target attainment is likely with a range of MIC values.
PMID: 25632974 [PubMed - as supplied by publisher]