Amoxicillin therapeutic drug monitoring for endocarditis: A comparative study (EI-STAB)

Int J Antimicrob Agents. 2023 Jul;62(1):106821. doi: 10.1016/j.ijantimicag.2023.106821. Epub 2023 Apr 21.

Abstract

Introduction: International guidelines recommend high doses of β-lactams for most cases of infective endocarditis (IE). Therapeutic drug monitoring (TDM) is increasingly used to adjust β-lactam dose based on plasma concentrations, although there are no comparative studies to support this practice. The benefit of amoxicillin TDM during IE was evaluated.

Methods: An observational, retrospective, cohort study of adults treated with high-dose amoxicillin for enterococcal or streptococcal IE was conducted in two referral centers. Patients with, or without TDM were compared. The primary outcome was mean daily amoxicillin dose.

Results: A total of 206 cases of streptococcal (n=140, 68%) or enterococcal (n=66, 32%) IE were included. IE occurred on prosthetic valves in 77 (37%) cases, and on intracardiac devices in 28 (14%) cases. Aortic valve was involved in 136 (66%) cases. There were 154 men (75%), mean age was 70 ± 14 years, valve surgery was performed in 81/206 (39%) patients, and in-hospital mortality was 8% (17/206). All patients in the TDM group and most patients in the group without TDM received amoxicillin as continuous infusion. Amoxicillin TDM was performed for 114 patients (55.3%), with a mean of 4.7 ± 2.3 measures per patient, a mean plasma steady-state concentration of 41.2 ± 19 mg/L, most (82/114, 72%) being within the therapeutic target (20-80 mg/L). Mean amoxicillin dose was lower in patients with TDM (10.0 ± 3.3 g/day) than those without TDM (11.3 ± 2.0 g/day) (P=0.003).

Conclusion: Amoxicillin TDM was associated with a reduction in daily doses, with no impact on adverse events and prognosis. Individualized treatment of IE through TDM may contribute to decreased use of antibiotics.

Keywords: Amoxicillin; Enterocococcus; Infective endocarditis; Streptococcus; Therapeutic drug monitoring.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amoxicillin / therapeutic use
  • Anti-Bacterial Agents / therapeutic use
  • Cohort Studies
  • Drug Monitoring
  • Endocarditis* / drug therapy
  • Endocarditis, Bacterial* / drug therapy
  • Enterococcus
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Streptococcus
  • beta-Lactams / therapeutic use

Substances

  • Amoxicillin
  • Anti-Bacterial Agents
  • beta-Lactams