Defining the pharmacokinetic/pharmacodynamic index of piperacillin/tazobactam within a hollow-fibre infection model to determine target attainment in intensive care patients.

Autor: Wenker SAM; Infection, Immunity and Inflammation Department, Great Ormond Street Institute of Child Health, University College London, London, UK.; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden University, Leiden, The Netherlands., Alabdulkarim N; Infection, Immunity and Inflammation Department, Great Ormond Street Institute of Child Health, University College London, London, UK.; Department of Clinical Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia., Readman JB; Infection, Immunity and Inflammation Department, Great Ormond Street Institute of Child Health, University College London, London, UK., Slob EMA; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden University, Leiden, The Netherlands.; Department of Clinical Pharmacy, Haaglanden Medical Center, The Hague, The Netherlands., Satta G; Department of Infection, University College London Hospitals NHS Foundation Trust, London, UK., Ali S; Environmental Research Laboratory, University College London Hospitals NHS Foundation Trust, London, UK., Gadher N; Pharmacy Department, CMORE, University College London Hospitals NHS Foundation Trust, London, UK., Shulman R; Pharmacy Department, CMORE, University College London Hospitals NHS Foundation Trust, London, UK., Standing JF; Infection, Immunity and Inflammation Department, Great Ormond Street Institute of Child Health, University College London, London, UK.; Department of Pharmacy, Great Ormond Street Hospital for Children, London, UK.
Jazyk: angličtina
Zdroj: JAC-antimicrobial resistance [JAC Antimicrob Resist] 2024 Mar 12; Vol. 6 (2), pp. dlae036. Date of Electronic Publication: 2024 Mar 12 (Print Publication: 2024).
DOI: 10.1093/jacamr/dlae036
Abstrakt: Background: It is important to optimize dosing schemes of antibiotics to maximize the probability of therapeutic success. The recommended pharmacokinetic/pharmacodynamic (PK/PD) index for piperacillin/tazobactam therapy in clinical studies ranges widely (50%-100% fT >1-4×MIC ). Dosing schemes failing to achieve PK/PD targets may lead to negative treatment outcomes.
Objectives: The first aim of this study was to define the optimal PK/PD index of piperacillin/tazobactam with a hollow-fibre infection model (HFIM). The second aim was to predict whether these PK/PD targets are currently achieved in critically ill patients through PK/PD model simulation.
Patients and Methods: A dose-fractionation study comprising 21 HFIM experiments was performed against a range of Gram-negative bacterial pathogens, doses and infusion times. Clinical data and dose histories from a case series of nine patients with a known bacterial infection treated with piperacillin/tazobactam in the ICU were collected. The PK/PD index and predicted plasma concentrations and therefore target attainment of the patients were simulated using R version 4.2.1.
Results: fT >MIC was found to be the best-fitting PK/PD index for piperacillin/tazobactam. Bactericidal activity with 2 log 10  cfu reduction was associated with 77% fT >MIC . Piperacillin/tazobactam therapy was defined as clinically 'ineffective' in ∼78% (7/9) patients. Around seventy-one percent (5/7) of these patients had a probability of >10% that 2  log 10  cfu reduction was not attained.
Conclusions: Our dose-fractionation study indicates an optimal PK/PD target in piperacillin/tazobactam therapies should be 77% fT >MIC for 2 log 10 kill. Doses to achieve this target should be considered when treating patients in ICU.
(© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)
Databáze: MEDLINE
Externí odkaz: