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

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 Cmax (maximum serum concentration) in the fasted and fed states were 5.1 ug/ml versus 3.3 ug/ml, respectively ( P < 0.0 0 01; 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). Opti-mized dosing led to a per-patient median rifampicin dosing of 24.6 mg/kg and a median Cmax increase from 2.4 ug/ml to 17.8 ug/ml ( P-value = 0.0 0 05; 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 feed-ing. TDM-guided dose escalation provided an effective strategy to achieve target drug exposure in these critically ill patients with TB. (c) 2022 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

This study investigates the pharmacokinetics of rifampicin and the impact of continuous enteral feeding on drug absorption in critically ill patients with tuberculosis. Therapeutic drug monitoring (TDM) with dose escalation is found to be an effective strategy to achieve target drug exposure in these patients.