Title :

Parameters influencing the pharmacokinetics/pharmacodynamics of piperacillin/tazobactam in patients with febrile neutropenia and haematological malignancy: a prospective study

Author(s) :

Benech, Nicolas [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Dumitrescu, Oana [Auteur]
Pathogénie des Staphylocoques – Staphylococcal Pathogenesis [CIRI] [CIRI-StaPath]
Conrad, Anne [Auteur]
Pathogenèse des légionelles- Legionella pathogenesis [CIRI] [CIRI-LegioPath]
Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL]
Balsat, Marie [Auteur]
Recherche clinique appliquée à l'hématologie [(EA_3518)]
Paubelle, Etienne [Auteur]
CHU Amiens-Picardie
Ducastelle-Lepretre, Sophie [Auteur]
Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL]
Ducastelle-Leprêtre, Sophie [Auteur]
Centre Hospitalier Lyon Sud [CHU - HCL] [CHLS]
Labussière-Wallet, Hélène [Auteur]
Hospices Civils de Lyon [HCL]
Salles, Gilles [Auteur]
Laboratoire de Biologie Moléculaire de la Cellule [LBMC]
Centre Hospitalier Lyon Sud [CHU - HCL] [CHLS]
Cohen, Sabine [Auteur]
Goutelle, Sylvain [Auteur]
Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 [LBBE]
Université Claude Bernard Lyon 1 [UCBL]
Evaluation et modélisation des effets thérapeutiques [LBBE]
Hospices Civils de Lyon [HCL]
Université Claude Bernard Lyon 1 - Institut des Sciences Pharmaceutiques et Biologiques [UCBL ISPB]
Ader, Florence [Auteur]
Hospices Civils de Lyon [HCL]
Centre International de Recherche en Infectiologie [CIRI]
Hôpital Edouard Herriot [CHU - HCL]
Hôpital de la Croix-Rousse [CHU - HCL]
Center for Interdisciplinary Research and Innovation [CIRI]
Alcazer, V [Auteur]
Bachy, E [Auteur]
Barraco, F [Auteur]
Boccard, M [Auteur]
Billaud, G [Auteur]
Chidiac, C [Auteur]
Dupont, D [Auteur]
Escuret, V [Auteur]
Ferry, T [Auteur]
Frobert, E [Auteur]
Ghesquières, H [Auteur]
Heiblig, M [Auteur]
Larcher, M-V [Auteur]
Laurent, F [Auteur]
Lina, B [Auteur]
Lina, G [Auteur]
Menotti, J [Auteur]
Miailhes, P [Auteur]
Monneret, G [Auteur]
Morfin-Sherpa, F [Auteur]
Perpoint, T [Auteur]
Rabodonirina, M [Auteur]
Renault, M [Auteur]
Roure-Sobas, C [Auteur]
Thomas, X [Auteur]
Valour, F [Auteur]
Venet, F [Auteur]
Wallet, F [Auteur]
Wallon, M [Auteur]

Journal title :

Journal of Antimicrobial Chemotherapy

Pages :

2676-2680

Publisher :

Oxford University Press (OUP)

Publication date :

2019-09-01

ISSN :

0305-7453

HAL domain(s) :

Sciences du Vivant [q-bio]/Sciences pharmaceutiques/Pharmacologie

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL