2560. Individual Meropenem Epithelial Lining Fluid and Plasma PK/PD Target Attainment in Patients with Pneumonia
Authors: Rohani Roxane , Yarnold Paul R , Scheetz Marc H , Neely Michael N , Kang Mengjia , Donnelly Helen K , Dedicatoria Kay , Nozick Sophia , Medernach Rachel , Hauser Alan R , Ozer Egon A , Diaz Estefani , Misharin Alexander V , Wunderink Richard G , Rhodes Nathaniel J 
Published: November 2023

Abstract

Background
Whether pharmacokinetic (PK)/pharmacodynamic (PD) target attainment for meropenem measured in plasma is a clinically reliable surrogate for target attainment in the epithelial lining fluid (ELF) in pneumonia is unclear. The objective of the current study was to characterize target attainment in plasma and ELF using prospectively collected samples and to define predictors of optimal target attainment.

Methods
Individual Bayesian meropenem plasma and ELF profiles were generated using Pmetrics for the first 24 hours of treatment. First 24-hr PK/PD target attainment was evaluated vs. PK/PD goals of 100% T&gt;1xMIC and 100% T&gt;4xMIC for a susceptible MIC of 2 mg/L.

Results
Sixty-seven patients contributed ELF and plasma PK data (range: 1-3 samples/patient for each matrix). Mean population CL, Vplasma, and VELF estimates were 6.2 L/hr, 45.7, and 28.3 L. For the 100% T&gt;4xMIC goal the following target attainment groups were identified: optimal (≥95%) in plasma and ELF (n=27/67, 40%), near-optimal ( &gt;50% and &lt; 95%) in both plasma and ELF (n=11/67, 16.4%), suboptimal (&lt; 50%) in ELF only (n=15/67, 22.4%), suboptimal (&lt; 50%) in plasma only (n=1/67, 1.5%), and suboptimal (&lt; 50%) in both ELF and plasma (n=13, 19.4%). Loading doses significantly improved the likelihood of optimal vs. suboptimal target attainment in ELF and plasma (96.2% vs. 14.3%; p&lt; 0.0001) but did not reliably discriminate other groups.
Individual observed meropenem (ordinate) and model predicted meropenem (abscissa) concentrations in plasma (A) and ELF (B) in patients with pneumonia.Panel A.) grouping according to a 1xMIC target. A total of 53 patients had optimal (green) attainment in both plasma and ELF, 9 patients had near optimal attainment in plasma and ELF (gold), 3 had suboptimal attainment in ELF only (red), and 2 had suboptimal attainment in both plasma and ELF (purple). Panel B.) grouping according to a 4xMIC target. A total of 27 patients had optimal (green) attainment in both plasma and ELF, 11 patients had near optimal attainment in plasma and ELF (gold), 1 patient had suboptimal attainment in plasma only (blue), 15 had suboptimal attainment in ELF only (red), and 13 had suboptimal attainment in both plasma and ELF (purple).

Conclusion
Optimal target attainment was achieved in only 40% of patients while nearly 20% of patients had suboptimal attainment in both plasma and ELF. Use of plasma as a surrogate for ELF would miss up to 20% of patients with suboptimal ELF attainment, suggesting that therapeutic monitoring of ELF may be required in some patients to optimize PK/PD attainment.

Disclosures
Marc H. Scheetz, PharmD, MSc, Abbvie: Advisor/Consultant|ASHP: Honoraria|Chambless, Higdon, Richardson, Katz & Griggs, LLP: Expert Testimony|Cidara: Advisor/Consultant|Entasis: Advisor/Consultant|F2G: Advisor/Consultant|GSK: Advisor/Consultant|Guidepoint Global: Honoraria|Hall, Booth, Smith, P.C.: Expert Testimony|Merck: Advisor/Consultant|Reminger Co., L.P.A: Expert Testimony|Spero: Advisor/Consultant|Takeda: Advisor/Consultant|Taylor, English, Duma, LLP: Expert Testimony|Third Pole Therapeutics: Advisor/Consultant Michael N. Neely, MD, Astellas Pharma Global Development, Inc.: Advisor/Consultant|Astellas Pharma Global Development, Inc.: Support for the present publication Richard G. Wunderink, MD, bioMerieux: Honoraria|Kariius: Clinical Evaluation Committee|LaJolla: Advisor/Consultant|Pfizer, Inc: Clinical Evaluation Committee|Shionogi: Advisor/Consultant Nathaniel J. Rhodes, PharmD MS, Third Pole Therapeutics: Advisor/Consultant