Therapeutic drug monitoring of high-dosage intravenous flucloxacillin and mortality in patients with Staphylococcus aureus bacteremia: a retrospective cohort study using inverse probability weighting
In brief
Therapeutic drug monitoring lowered 90-day mortality from 39% to 27%
In a retrospective cohort of 285 patients with Staphylococcus aureus bacteremia, TDM-guided flucloxacillin dosing reduced the daily dose by about 2.3 g and was associated with a drop in 90-day mortality from 39% to 27%, though the difference did not reach statistical significance. No clear benefit on kidney injury, liver injury, or hypokalemia was observed, leaving the clinical advantage of TDM uncertain.
- Journal
- European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology (Q1)
- Published
- 10 September 2026
- Study design
- Retrospective cohort
- Evidence level
- Level 3, Low (CEBM 3b)
- Authors
- D T P Buis, J L Wu, S Douiyeb, C H van Werkhoven, J M Prins, T W van der Vaart, et al.
- PMID
- 42722972
- DOI
- 10.1007/s10096-026-05670-7
Why clinicians should know about it
- Picked for Internal Medicine (paper of the day, 14 September 2026): TDM reduces dosage without mortality benefit
Abstract
PURPOSE: Despite the increasing use of TDM, data on its effect on relevant patient outcomes for anti-staphylococcal penicillins (ASPs) remain scarce. METHODS: We performed a retrospective study using data from two Dutch cohorts of patients with Staphylococcus aureus bacteremia (SAB). Patients with MSSA bacteremia who started with the equivalent of flucloxacillin 12 g/24 h within seven days after the first positive blood culture were included. We compared the effects of a TDM-based dosing strategy versus a fixed-dosage strategy during high-dosage flucloxacillin therapy. Primary outcome was 90-day all-cause mortality. Secondary outcomes included incidence of antibiotic-associated adverse events and antibiotic consumption. We fitted a marginal structural model using inverse probability weighting to adjust for confounding (i.e. age, Charlson Comorbidity Index, persistent bacteremia, dominant focus of infection and ICU admission), time-dependent bias and exposure-confounder feedback. RESULTS: We included 285 patients of whom 132 were treated with a TDM-based dosing strategy and 153 with a fixed-dosage strategy. TDM-based dosing was on average associated with a 2.30 gram (95% CI 1.90-2.71) lower daily flucloxacillin dosage than a fixed-dosage regimen. In the TDM group 90-day all-cause mortality was 27% and in the fixed-dosage group 39%. In adjusted analyses, TDM-based dosing was not significantly associated with reduced mortality (HR 0.69, 0.46-1.05) nor with AKI (HR 1.41, 0.89-2.23), DILI (HR 1.79, 0.42-7.68) or hypokalemia (HR 0.90, 0.54-1.48). CONCLUSION: TDM in patients with SAB treated with high-dosage ASPs is associated with lower antibiotic consumption without a statistically significant difference in mortality. We found no evidence of a decrease in antibiotic-associated adverse events.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.