1. Parameters influencing the pharmacokinetics/pharmacodynamics of piperacillin/tazobactam in patients with febrile neutropenia and haematological malignancy: a prospective study.
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Benech, Nicolas, Dumitrescu, Oana, Conrad, Anne, Balsat, Marie, Paubelle, Etienne, Ducastelle-Lepretre, Sophie, Labussière-Wallet, Hélène, Salles, Gilles, Cohen, Sabine, Goutelle, Sylvain, Ader, Florence, Group, Lyon HEMINF Study, and Lyon HEMINF Study Group
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FEBRILE neutropenia , *PHARMACOKINETICS , *LONGITUDINAL method , *PIPERACILLIN , *LEUKAPHERESIS , *ALKALINE phosphatase , *INTRAVENOUS therapy , *BETA-lactamase inhibitors - Abstract
Objectives: To assess population pharmacokinetics (PK) and pharmacodynamics (PD) of both piperacillin and tazobactam in neutropenia patients and examine dosage requirements related to the MIC distribution for Gram-negative bacteria involved in bloodstream infections (BSIs).Methods: We conducted a prospective study including adult haematological malignancy patients with febrile neutropenia receiving piperacillin/tazobactam as short (30 min) or prolonged (4 h) intravenous infusions. Concentration data were analysed using a population approach. Dosing simulations with the final model investigated factors influencing the PK/PD of piperacillin/tazobactam quantified by fT>MIC or PTA for piperacillin and tazobactam, respectively. In parallel, the local MIC distribution of β-lactams was documented for Gram-negative bacteria involved in BSIs.Results: Over 10 months, 31 patients were enrolled, with 11 (35.5%) short and 20 (64.5%) prolonged infusion regimens. A one-compartment model adequately described the data for both drugs. Prolonged infusion, increased serum alkaline phosphatase (ALP) values and renal function impairment were associated with increased piperacillin fT>MIC. For patients with normal or augmented renal CL, dosing regimens q8h or q6h with 30 min of infusion were insufficient to achieve acceptable PTA for piperacillin/tazobactam at the median MIC value of 8 mg/L. Prolonged infusion of large doses was associated with the best PTA for both piperacillin and tazobactam.Conclusions: In a population of haematological malignancy patients with neutropenia, renal function and ALP influenced the PK of piperacillin/tazobactam. Prolonged intravenous infusion would optimize the PK of piperacillin/tazobactam, especially in the case of augmented renal CL and/or low-range bacterial susceptibility. [ABSTRACT FROM AUTHOR]- Published
- 2019
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