Individual meropenem epithelial lining fluid and plasma PK/PD target attainment.

Autor: Rohani R; Discipline of Cellular and Molecular Pharmacology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA., Yarnold PR; Optimal Data Analysis, LLC, Chicago, Illinois, USA., Scheetz MH; Department of Pharmacy Practice, Midwestern University, Chicago College of Pharmacy, Downers Grove, Illinois, USA.; Pharmacometrics Center of Excellence, Midwestern University, Downers Grove, Illinois, USA.; Department of Pharmacy, Northwestern Memorial Hospital, Chicago, Illinois, USA., Neely MN; Laboratory of Applied Pharmacokinetics and Bioinformatics, The Saban Research Institute, Children's Hospital of Los Angeles, Los Angeles, California, USA.; Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Kang M; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Donnelly HK; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Dedicatoria K; Department of Pharmacy Practice, Midwestern University, Chicago College of Pharmacy, Downers Grove, Illinois, USA., Nozick SH; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Medernach RL; Division of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Hauser AR; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Division of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Ozer EA; Division of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Center for Pathogen Genomics and Microbial Evolution, Havey Institute for Global Health, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA., Diaz E; Robert H. Lurie Comprehensive Cancer Research Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA., Misharin AV; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Wunderink RG; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Rhodes NJ; Department of Pharmacy Practice, Midwestern University, Chicago College of Pharmacy, Downers Grove, Illinois, USA.; Pharmacometrics Center of Excellence, Midwestern University, Downers Grove, Illinois, USA.; Department of Pharmacy, Northwestern Memorial Hospital, Chicago, Illinois, USA.
Jazyk: angličtina
Zdroj: Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2023 Dec 14; Vol. 67 (12), pp. e0072723. Date of Electronic Publication: 2023 Nov 17.
DOI: 10.1128/aac.00727-23
Abstrakt: It is unclear whether plasma is a reliable surrogate for target attainment in the epithelial lining fluid (ELF). The objective of this study was to characterize meropenem target attainment in plasma and ELF using prospective samples. The first 24-hour T >MIC was evaluated vs 1xMIC and 4xMIC targets at the patient (i.e., fixed MIC of 2 mg/L) and population [i.e., cumulative fraction of response (CFR) according to EUCAST MIC distributions] levels for both plasma and ELF. Among 65 patients receiving ≥24 hours of treatment, 40% of patients failed to achieve >50% T >4xMIC in plasma and ELF, and 30% of patients who achieved >50% T >4xMIC in plasma had <50% T >4xMIC in ELF. At 1xMIC and 4xMIC targets, 3% and 25% of patients with >95% T >MIC in plasma had <50% T >MIC in ELF, respectively. Those with a CRCL >115 mL/min were less likely to achieve >50%T >4xMIC in ELF ( P < 0.025). In the population, CFR for Escherichia coli at 1xMIC and 4xMIC was >97%. For Pseudomonas aeruginosa , CFR was ≥90% in plasma and ranged 80%-85% in ELF at 1xMIC when a loading dose was applied. CFR was reduced in plasma (range: 75%-81%) and ELF (range: 44%-60%) in the absence of a loading dose at 1xMIC. At 4xMIC, CFR for P. aeruginosa was 60%-86% with a loading dose and 18%-62% without a loading dose. We found that plasma overestimated ELF target attainment inup to 30% of meropenem-treated patients, CRCL >115 mL/min decreased target attainment in ELF, and loading doses increased CFR in the population.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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