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

Rubeshan Perumal; Kogieleum Naidoo; Anushka Naidoo; Marothi P Letsoalo; Aliasgar Esmail; Ivan Joubert; Paolo Denti; Lubbe Wiesner; Nesri Padayatchi; Gary Maartens; Keertan Dheda

doi:10.1016/j.ijid.2022.11.033

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

Int J Infect Dis. 2023 Jan:126:174-180. doi: 10.1016/j.ijid.2022.11.033. Epub 2022 Dec 1.

Authors

Affiliations

¹ Centre for Lung Infection and Immunity Unit, Division of Pulmonology, Department of Medicine and University of Cape Town Lung Institute, University of Cape Town, Cape Town, South Africa; Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, South Africa Medical Research Council-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, University of KwaZulu-Natal, Durban, South Africa; Medical Research Council-Centre for the AIDS Programme of Research in South Africa HIV-TB Pathogenesis and Treatment Research Unit, University of KwaZulu-Natal, Durban, South Africa.
² Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, South Africa Medical Research Council-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, University of KwaZulu-Natal, Durban, South Africa; Medical Research Council-Centre for the AIDS Programme of Research in South Africa HIV-TB Pathogenesis and Treatment Research Unit, University of KwaZulu-Natal, Durban, South Africa.
³ Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, South Africa Medical Research Council-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, University of KwaZulu-Natal, Durban, South Africa.
⁴ Centre for Lung Infection and Immunity Unit, Division of Pulmonology, Department of Medicine and University of Cape Town Lung Institute, University of Cape Town, Cape Town, South Africa.
⁵ Division of Critical Care Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.
⁶ Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
⁷ Centre for Lung Infection and Immunity Unit, Division of Pulmonology, Department of Medicine and University of Cape Town Lung Institute, University of Cape Town, Cape Town, South Africa; South African Medical Research Council Centre for the Study of Antimicrobial Resistance, University of Cape Town, Cape Town, South Africa; Faculty of Infectious and Tropical Diseases, Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom. Electronic address: Keertan.dheda@uct.ac.za.

PMID: 36462574
DOI: 10.1016/j.ijid.2022.11.033

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.

Keywords: Critical illness; Dose-adjustment; High-dose rifampicin; Personalized medicine; Pharmacokinetics.

MeSH terms

Critical Illness
Drug Monitoring
Drug Therapy, Combination
Enteral Nutrition
Humans
Rifampin*
Tuberculosis* / drug therapy

Substances

Rifampin

Abstract

MeSH terms

Substances

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