Population pharmacokinetics of fluconazole in critically ill patients receiving extracorporeal membrane oxygenation and continuous renal replacement therapy: an ASAP ECMO study.

Autor: Novy E; Faculty of Medicine, University of Queensland Centre for Clinical Research (UQCCR), The University of Queensland , Brisbane, Queensland, Australia.; Université de Lorraine, SIMPA , Nancy, France.; Departement of anesthesiology, Critical care and peri-operative medicine, University hospital of Nancy , Nancy, France., Abdul-Aziz MH; Faculty of Medicine, University of Queensland Centre for Clinical Research (UQCCR), The University of Queensland , Brisbane, Queensland, Australia., Cheng V; Faculty of Medicine, University of Queensland Centre for Clinical Research (UQCCR), The University of Queensland , Brisbane, Queensland, Australia., Burrows F; Department of Pharmacy, St. Vincent's Hospital , Sydney, New South Wales, Australia., Buscher H; Department of Intensive Care Medicine, St. Vincent's Hospital , Sydney, New South Wales, Australia.; University of New South Wales, St Vincent's Centre for Applied Medical Research , Sydney, New South Wales, Australia., Corley A; The Prince Charles Hospital, Critical Care Research Group and Adult Intensive Care Services , Brisbane, Queensland, Australia., Diehl A; Department of Intensive Care and Hyperbaric Medicine, The Alfred Hospital and School of Public Health and Preventive Medicine, Monash University , Melbourne, Victoria, Australia., Gilder E; Cardiothoracic and Vascular Intensive Care Unit, Auckland City Hospital , Auckland, New Zealand., Levkovich BJ; Experiential Development and Graduate Education and Centre for Medicines Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University , Melbourne, Victoria, Australia., McGuinness S; Cardiothoracic and Vascular Intensive Care Unit, Auckland City Hospital , Auckland, New Zealand., Ordonez J; Faculty of Medicine, University of Queensland Centre for Clinical Research (UQCCR), The University of Queensland , Brisbane, Queensland, Australia., Parke R; Cardiothoracic and Vascular Intensive Care Unit, Auckland City Hospital , Auckland, New Zealand.; The University of Auckland, School of Nursing , Auckland, New Zealand., Parker S; Faculty of Medicine, University of Queensland Centre for Clinical Research (UQCCR), The University of Queensland , Brisbane, Queensland, Australia., Pellegrino V; Department of Intensive Care and Hyperbaric Medicine, The Alfred Hospital and School of Public Health and Preventive Medicine, Monash University , Melbourne, Victoria, Australia., Reynolds C; Department of Intensive Care Medicine, St. Vincent's Hospital , Sydney, New South Wales, Australia., Rudham S; Department of Intensive Care Medicine, St. Vincent's Hospital , Sydney, New South Wales, Australia., Wallis SC; Faculty of Medicine, University of Queensland Centre for Clinical Research (UQCCR), The University of Queensland , Brisbane, Queensland, Australia., Welch SA; Department of Pharmacy, St. Vincent's Hospital , Sydney, New South Wales, Australia., Fraser JF; The Prince Charles Hospital, Critical Care Research Group and Adult Intensive Care Services , Brisbane, Queensland, Australia.; Faculty of Medicine, The University of Queensland , Brisbane, Queensland, Australia.; Faculty of Health, Queensland University of Technology , Brisbane, Queensland, Australia.; Faculty of Health Sciences and Medicine, Bond University , Gold Coast, Queensland, Australia., Shekar K; The Prince Charles Hospital, Critical Care Research Group and Adult Intensive Care Services , Brisbane, Queensland, Australia.; Faculty of Health, Queensland University of Technology , Brisbane, Queensland, Australia.; Faculty of Health Sciences and Medicine, Bond University , Gold Coast, Queensland, Australia., Roberts JA; Faculty of Medicine, University of Queensland Centre for Clinical Research (UQCCR), The University of Queensland , Brisbane, Queensland, Australia.; Department of Intensive Care Medicine and Pharmacy, Royal Brisbane and Women's Hospital , Brisbane, Queensland, Australia.; Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier , Nîmes, France.
Jazyk: angličtina
Zdroj: Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2024 Jan 10; Vol. 68 (1), pp. e0120123. Date of Electronic Publication: 2023 Dec 08.
DOI: 10.1128/aac.01201-23
Abstrakt: This multicenter study describes the population pharmacokinetics (PK) of fluconazole in critically ill patients receiving concomitant extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) and includes an evaluation of different fluconazole dosing regimens for achievement of target exposure associated with maximal efficacy. Serial blood samples were obtained from critically ill patients on ECMO and CRRT receiving fluconazole. Total fluconazole concentrations were measured in plasma using a validated chromatographic assay. A population PK model was developed and Monte Carlo dosing simulations were performed using Pmetrics in R. The probability of target attainment (PTA) of various dosing regimens to achieve fluconazole area under the curve to minimal inhibitory concentration ratio (AUC 0-24 /MIC) >100 was estimated. Eight critically ill patients receiving concomitant ECMO and CRRT were included. A two-compartment model including total body weight as a covariate on clearance adequately described the data. The mean (±standard deviation, SD) clearance and volume of distribution were 2.87 ± 0.63 L/h and 15.90 ± 13.29 L, respectively. Dosing simulations showed that current guidelines (initial loading dose of 12 mg/kg then 6 mg/kg q24h) achieved >90% of PTA for a MIC up to 1 mg/L. None of the tested dosing regimens achieved 90% of PTA for MIC above 2 mg/L. Current fluconazole dosing regimen guidelines achieved >90% PTA only for Candida species with MIC <1 mg/L and thus should be only used for Candida-documented infections in critically ill patients receiving concomitant ECMO and CRRT. Total body weight should be considered for fluconazole dose.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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