The impact of enteral feeding and therapeutic monitoring of rifampicin with dose escalation in critically ill patients with tuberculosis
Year: 2022
Type: article
Abstract: 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.
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,200
Funders: Wellcome Trust, National Institutes of Health, Medical Research Council, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, European and Developing Countries Clinical Trials Partnership
Awards: G2845561747, G3102268938, The Individualized Multi-/Extensively Drug-Resistant Tuberculosis Treatment Strategy Study, Novel biomarkers predictive of susceptibility and treatment response in patients with MDR-TB, G5934716681, International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group, G7133735795, G7872987505, A lung-oriented controlled human infection model using live BCG to evaluate tuberculosis immunopathogenicity and vaccine efficacy (TB-CHIM)., Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections, AIDS Clinical Trial Group Laboratory Center, Statistical and Data Management Center (SDMC), Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG)
OpenAlex ID: W4310668495