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

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ID: 278098
2023
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Abstract
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 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 in plasma and ELF, and 30% of patients who achieved >50% T in plasma had <50% T in ELF. At 1xMIC and 4xMIC targets, 3% and 25% of patients with >95% T in plasma had <50% T in ELF, respectively. Those with a CRCL >115 mL/min were less likely to achieve >50%T in ELF ( < 0.025). In the population, CFR for at 1xMIC and 4xMIC was >97%. For , 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 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.
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rohani2023individualantimicrobial Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Rohani, Roxane;Yarnold, Paul R;Scheetz, Marc H;Neely, Michael N;Kang, Mengjia;Donnelly, Helen K;Dedicatoria, Kay;Nozick, Sophie H;Medernach, Rachel L;Hauser, Alan R;Ozer, Egon A;Diaz, Estefani;Misharin, Alexander V;Wunderink, Richard G;Rhodes, Nathaniel J;
Journal Antimicrobial agents and chemotherapy
Year 2023
DOI
e00727-23
URL
Keywords
hospital-acquired pneumonia maximum-accuracy predictive model pharmacokinetics, pharmacodynamics

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