Study shows low rifampicin levels in critically ill TB patients in ICU

7 March 2023

The study on The impact of enteral feeding and therapeutic monitoring of Rifampicin with dose escalation in critically ill patients with tuberculosis, demonstrated low rifampicin concentrations in most of the critically ill patients receiving standard treatment, irrespective of feeding status at the time of drug administration. Results from a randomised sequential pharmacokinetic study, led by CAPRISA researchers to determine the frequency of low plasma concentrations of rifampicin in critically ill patients with TB, the effect of feeding on drug exposure, and the effect of dose-escalation (TDM) on pharmacokinetic target attainment, was published in the International Journal of Infectious Diseases. 

TB drug concentrations are frequently below the recommended therapeutic concentrations in critically ill patients with active TB. The study involved two intensive sessions of pharmacokinetic sampling on consecutive days in adult patients on drug-susceptible TB treatment.  Among 20 critically ill patients (40% HIV-infected), median rifampicin Cmax  (maximum serum concentration) in the fasted and fed states were 5.1µg/mL versus 3.3µg/mL, respectively [p <0.0001; geometric-mean-ratio (GMR) 1.95; 90%CI 1.46-2.60]. 

The proportion of patients with low rifampicin concentrations in the fasted and fed states was 80% versus 100% (p=0.1336). Optimized dosing led to a per-patient median rifampicin dosing of 24.6mg/kg, and median Cmax increase from 2.4µg/mL to 17.8µg/mL (p=0.0005; GMR 8.29; 90%CI 3.88-17.74).  TDM-guided dose-escalation increased the proportion of patients achieving the suggested target rifampicin concentration compared to standard dosing (83% versus 0%, p=0.004). 

The researchers concluded a higher starting dose and the use of TDM may significantly improve the pharmacokinetic- pharmacodynamic profiles and treatment outcomes in critically ill patients.

For further reading see: Perumal R, et al. Int J Infect Dis. 2023. doi: 10.1016/j.ijid.2022.11.033. 

Figure: Comparison of maximum rifampicin concentrations on standard dosing (fed and fasted) and optimised dosing. Standard dosing in the fed state (blue), standard dosing in the fasted state (red), optimised dosing (orange). Dashed horizontal line represents the minimum concentration threshold: 8 µg/mL. Solid horizontal lines represent median values.