Determinants of beta-lactam PK/PD target attainment in critically ill patients: A single center retrospective study

J Crit Care. 2024 Oct:83:154828. doi: 10.1016/j.jcrc.2024.154828. Epub 2024 May 17.

Abstract

Purpose: We aimed to identify factors associated with achieving target BL plasma concentrations and describe real world data for therapeutic drug monitoring (TDM).

Methods: A retrospective single center study was conducted. We collected data from patients admitted to ICU with at least one BL TDM. We assessed the proportion of patients attaining the recommended plasma concentrations (i.e 100%fT > 4 to 8 MIC). Univariate and multivariate analyses was performed to identify the determinants of BL target attainment.

Results: 156 patients were included. At the first dosing, 34% achieved target BL plasma concentrations, 50% were overdosed, and 16% were underdosed. Median time for 1st TDM were 4 (SD = 2.9) days. Multivariate analysis revealed that CKD-EPI estimated glomerular filtration rate (OR = 1.02; CI [1.01; 1.03]; p < 0.0001) and total body weight (OR = 1.03; CI [1.01; 1.04]; p = 0.0048) were the main determinant of BL target attainment. Conversely, Continuous Renal Replacement Therapy (OR = 0.28; CI [0.09; 0.89]; p = 0.0318) and meropenem use (OR = 0.31; CI [0.14; 0.69]; p = 0.0041) were identified as risk factors for overdosing. No factor was associated with underdosing.

Conclusion: Achieving target BL plasma concentrations remains challenging in ICUs. Identifying predictive factors of BL target attainment would favor implementing rapid dosing optimization strategies in both under and overdosing high risk patients.

Keywords: Beta-lactams; Critically ill; ICU; Pharmacokinetics; Target attainment; Therapeutic drug monitoring.

MeSH terms

  • Aged
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / blood
  • Anti-Bacterial Agents* / pharmacokinetics
  • Critical Illness*
  • Drug Monitoring*
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Intensive Care Units*
  • Male
  • Middle Aged
  • Retrospective Studies
  • beta-Lactams* / administration & dosage
  • beta-Lactams* / pharmacokinetics
  • beta-Lactams* / therapeutic use

Substances

  • Anti-Bacterial Agents
  • beta-Lactams