Modelled target attainment after temocillin treatment in severe pneumonia: systemic and epithelial lining fluid pharmacokinetics of continuous versus intermittent infusions.
temocillin; pharmacokinetics; pneumonia; Epithelial lining fluid; Monte Carlo; breakpoints
Abstract :
[en] Objectives: To describe the population pharmacokinetics of temocillin administered via continuous versus intermittent infusion in critically ill patients with pneumonia. Secondary objectives included characterization of epithelial lining fluid (ELF)/plasma penetration ratios and determination of the probability of target attainment (PTA) for a range of MICs. Methods: Thirty-two mechanically ventilated patients who were treated for pneumonia with 6g of temocillin daily for in vitro sensitive pathogens were assigned either to the II (2g every 8h over 0.5h) or to the CI (6g over 24h after a loading dose of 2g) group. A population pharmacokinetic model was developed using unbound plasma and total ELF concentrations of temocillin and related Monte Carlo simulations were performed to assess PTAs. Results: The AUC(0-24) ELF/plasma penetration ratio was 0.73, at steady-state, for both modes of infusion and whatever the level of creatinine clearance. Monte Carlo simulations showed for the minimal pharmacodynamic (PD) targets of 50% T> 1X MIC (II group) and 100% T > 1X MIC (CI group), PK/PD breakpoints of 4 mg/L in plasma and 2 mg/L in ELF and 4mg/L in plasma and ELF, respectively. The breakpoint was 8 mg/L in ELF for both modes of infusion in patients with CL(CR)<60mL/min. Conclusion: While CI provides better PKPD indexes, the latter remain below available recommendations for systemic infections, except in case of moderate renal impairment, thereby warranting future clinical studies in order to determine the efficacy of temocillin in severe pneumonia.
Denooz, Raphaël ; Université de Liège - ULiège > Département de pharmacie > Pharmacocintéique et pharmacovigilence
Maes, Nathalie ; Centre Hospitalier Universitaire de Liège - CHU > > Service des informations médico économiques (SIME)
Descy, Julie ; Université de Liège - ULiège University Hospital of Liège Service de Microbiologie Clinique
Frippiat, Frédéric ; Université de Liège - ULiège University Hospital of Liège
Marchand, S.
Grégoire, N.
Language :
English
Title :
Modelled target attainment after temocillin treatment in severe pneumonia: systemic and epithelial lining fluid pharmacokinetics of continuous versus intermittent infusions.
Publication date :
2022
Journal title :
Antimicrobial Agents and Chemotherapy
ISSN :
0066-4804
eISSN :
1098-6596
Publisher :
American Society for Microbiology, Washington, United States - District of Columbia
Pages :
AAC0205221
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FIRS - CHU Liège. Fonds d'Investissement de Recherche Scientifique
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