Rifampicin drug monitoring in TB patients: new evidence for increased dosage?

The standard 10 mg/kg rifampicin (RIF) dose for TB treatment may be insufficient. Higher doses improve microbiological efficacy without increasing adverse effects. Therapeutic drug monitoring (TDM) may help to optimise RIF dosing by measuring 2, 4, and 6 h post-dose concentrations (C2, C4, C6) and area under the curve (AUC).This retrospective study included TB patients receiving RIF 10 mg/kg. TDM assessed C2, peak concentrations (Cmax), AUC and timing of Cmax. Patients achieving target Cmax (>8 mg/L) and AUC (>67.5 mg*h/L) were evaluated, and dosages were adjusted accordingly. Differences in AUC between TB disease and infection, as well as between diabetic and non-diabetic patients, were evaluated. Side effects were recorded.Among 181 patients, the median AUC was 57.9 mg*h/L. While 69.6% reached a Cmax >8 mg/L, only 40.9% met the target AUC. Delayed Cmax (at 4 or 6 h) occurred in 24.8% of patients. RIF doses were increased to a median of 14.1 mg/kg in 49.2% of patients, with no adverse events. After a follow-up of a median of 12 months, no new occurrence of TB disease was recorded.AUC-based TDM revealed suboptimal RIF exposure in many TB patients at standard doses, suggesting that higher doses are needed to improve treatment outcomes.