The impact of enteral feeding and therapeutic monitoring of rifampicin with dose escalation in critically ill patients with tuberculosis

Le résumé fourni par la source

Objectives Critically ill patients with tuberculosis (TB) face a high mortality risk and require effective treatment. There is a paucity of data on rifampicin pharmacokinetics, the impact of continuous enteral feeding on drug absorption, and the potential of therapeutic drug monitoring (TDM) to optimize drug exposure in these patients. Methods We performed a sequential pharmacokinetic study to determine the impact of feeding and TDM with rifampicin dose escalation in critically ill patients with TB. Noncompartmental pharmacokinetic analysis was performed. Results Among 20 critically ill patients (40% were HIV-infected), median rifampicin C max (maximum serum concentration) in the fasted and fed states were 5.1 µg/ml versus 3.3 µg/ml, respectively ( P <0.0001; geometric mean ratio 1.95; 90% confidence interval 1.46-2.60). The proportion of patients with low rifampicin concentrations in the fasted and fed states was 80% vs 100% ( P -value = 0.1336). Optimized dosing led to a per-patient median rifampicin dosing of 24.6 mg/kg and a median C max increase from 2.4 µg/ml to 17.8 µg/ml ( P -value = 0.0005; geometric mean ratio 8.29; 90% confidence interval 3.88-17.74). TDM-guided dose escalation increased the proportion of patients achieving the suggested target rifampicin concentration compared with standard dosing (83% vs 0%, P -value = 0.004). Conclusion We found low rifampicin concentrations in all patients receiving continuous enteral feeding. TDM-guided dose escalation provided an effective strategy to achieve target drug exposure in these critically ill patients with TB.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.