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

•First comparative study to evaluate therapeutic drug monitoring (TDM) in infective endocarditis (IE).•TDM enables a reduction in amoxicillin daily doses.•Amoxicillin recommended dosages for IE seem to be too high, particularly for streptococcal IE.•Individualized treatment for IE through TDM could decrease amoxicillin dose without prognosis concern. 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. 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. 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). 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.