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 opt...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | International Journal of Infectious Diseases |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1201971222006269 |
| _version_ | 1797977763160784896 |
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| author | Rubeshan Perumal Kogieleum Naidoo Anushka Naidoo Marothi P. Letsoalo Aliasgar Esmail Ivan Joubert Paolo Denti Lubbe Wiesner Nesri Padayatchi Gary Maartens Keertan Dheda |
| author_facet | Rubeshan Perumal Kogieleum Naidoo Anushka Naidoo Marothi P. Letsoalo Aliasgar Esmail Ivan Joubert Paolo Denti Lubbe Wiesner Nesri Padayatchi Gary Maartens Keertan Dheda |
| author_sort | Rubeshan Perumal |
| collection | DOAJ |
| description | 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 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 Cmax 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. |
| first_indexed | 2024-04-11T05:12:10Z |
| format | Article |
| id | doaj.art-af595979207841cfb5e12db2d19ed226 |
| institution | Directory Open Access Journal |
| issn | 1201-9712 |
| language | English |
| last_indexed | 2024-04-11T05:12:10Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Infectious Diseases |
| spelling | doaj.art-af595979207841cfb5e12db2d19ed2262022-12-25T04:16:55ZengElsevierInternational Journal of Infectious Diseases1201-97122023-01-01126174180The impact of enteral feeding and therapeutic monitoring of rifampicin with dose escalation in critically ill patients with tuberculosisRubeshan Perumal0Kogieleum Naidoo1Anushka Naidoo2Marothi P. Letsoalo3Aliasgar Esmail4Ivan Joubert5Paolo Denti6Lubbe Wiesner7Nesri Padayatchi8Gary Maartens9Keertan Dheda10Centre 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 AfricaCentre 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 AfricaCentre 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 AfricaCentre 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 AfricaCentre 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 AfricaDivision of Critical Care Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South AfricaDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South AfricaDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South AfricaCentre 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 AfricaDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South AfricaCentre 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; Corresponding author: Professor Keertan Dheda, Centre for Lung Infection and Immunity, Division of Pulmonology and UCT Lung Institute, H Floor, Room H 46.41, Old Main Building, Groote Schuur Drive, Groote Schuur Hospital, Observatory, Western Cape, 7925, Tel: +27 21 404 7654Objectives: 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 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 Cmax 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.http://www.sciencedirect.com/science/article/pii/S1201971222006269PharmacokineticsCritical illnessDose-adjustmentHigh-dose rifampicinPersonalized medicine |
| spellingShingle | Rubeshan Perumal Kogieleum Naidoo Anushka Naidoo Marothi P. Letsoalo Aliasgar Esmail Ivan Joubert Paolo Denti Lubbe Wiesner Nesri Padayatchi Gary Maartens Keertan Dheda The impact of enteral feeding and therapeutic monitoring of rifampicin with dose escalation in critically ill patients with tuberculosis International Journal of Infectious Diseases Pharmacokinetics Critical illness Dose-adjustment High-dose rifampicin Personalized medicine |
| title | The impact of enteral feeding and therapeutic monitoring of rifampicin with dose escalation in critically ill patients with tuberculosis |
| title_full | The impact of enteral feeding and therapeutic monitoring of rifampicin with dose escalation in critically ill patients with tuberculosis |
| title_fullStr | The impact of enteral feeding and therapeutic monitoring of rifampicin with dose escalation in critically ill patients with tuberculosis |
| title_full_unstemmed | The impact of enteral feeding and therapeutic monitoring of rifampicin with dose escalation in critically ill patients with tuberculosis |
| title_short | The impact of enteral feeding and therapeutic monitoring of rifampicin with dose escalation in critically ill patients with tuberculosis |
| title_sort | impact of enteral feeding and therapeutic monitoring of rifampicin with dose escalation in critically ill patients with tuberculosis |
| topic | Pharmacokinetics Critical illness Dose-adjustment High-dose rifampicin Personalized medicine |
| url | http://www.sciencedirect.com/science/article/pii/S1201971222006269 |
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