Pharmacokinetic and Pharmacodynamic Characteristics of Vancomycin and Meropenem in Critically Ill Patients Receiving Sustained Low-efficiency Dialysis

Clin Ther. 2020 Apr;42(4):625-633. doi: 10.1016/j.clinthera.2020.02.011. Epub 2020 Mar 19.

Abstract

Purpose: Antibiotic dosing is challenge in critically ill patients undergoing renal replacement therapy. Our aim was to evaluate the pharmacokinetic and pharmacodynamic (PK/PD) characteristics of meropenem and vancomycin in patients undergoing SLED.

Methods: Consecutive ICU patients undergoing SLED and receiving meropenem and/or vancomycin were prospectively evaluated. Serial blood samples were collected before, during, and at the end of SLED sessions. Antimicrobial concentrations were determined using a validated HPLC method. Noncompartmental PK analysis was performed. AUC was determined for vancomycin. For meropenem, time above MIC was calculated.

Findings: A total of 24 patients receiving vancomycin and 21 receiving meropenem were included; 170 plasma samples were obtained. Median serum vancomycin and meropenem concentrations before SLED were 24.5 and 28.0 μg/mL, respectively; after SLED, 14 and 6 μg/mL. Mean removal was 42% with vancomycin and 78% with meropenem. With vancomycin, 19 (83%), 16 (70%), and 15 (65%) patients would have achieved the target (AUC0-24 >400) considering MICs of 1, 2, and 4 mg/L, respectively. With meropenem, 17 (85%), 14 (70%), and 10 (50%) patients would have achieved the target (100% of time above MIC) if infected with isolates with MICs of 1, 4, and 8 mg/L, respectively.

Implications: SLED clearances of meropenem and vancomycin were 3-fold higher than the clearance described by continuous methods. Despite this finding, overall high PK/PD target attainments were obtained, except for at higher MICs. We suggest a maintenance dose of 1 g TID or BID of meropenem. With vancomycin, a more individualized approach using therapeutic drug monitoring should be used, as commercial assays are available.

Keywords: critical care; dialysis; drug monitoring; meropenem; vancomycin.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / pharmacology*
  • Critical Illness
  • Female
  • Humans
  • Hybrid Renal Replacement Therapy*
  • Intensive Care Units
  • Male
  • Meropenem / pharmacokinetics*
  • Meropenem / pharmacology*
  • Microbial Sensitivity Tests
  • Middle Aged
  • Vancomycin / pharmacokinetics*
  • Vancomycin / pharmacology*
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Vancomycin
  • Meropenem