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Parameters influencing the pharmacokinetics/pharmacodynamics of piperacillin/tazobactam in patients with febrile neutropenia and haematological malignancy: a prospective study.
- Source :
- Journal of Antimicrobial Chemotherapy (JAC); Sep2019, Vol. 74 Issue 9, p2676-2680, 5p
- Publication Year :
- 2019
-
Abstract
- <bold>Objectives: </bold>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).<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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]
Details
- Language :
- English
- ISSN :
- 03057453
- Volume :
- 74
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- Journal of Antimicrobial Chemotherapy (JAC)
- Publication Type :
- Academic Journal
- Accession number :
- 138251769
- Full Text :
- https://doi.org/10.1093/jac/dkz248