Shortened Tuberculosis Treatment Regimens: What is New?

Overview

Journal J Bras Pneumol

Specialty Pulmonary Medicine

Date 2020 Mar 28

PMID 32215450

Citations 15

Authors

Denise Rossato Silva

Fernanda Carvalho de Queiroz Mello

Giovanni Battista Migliori

Affiliations

Soon will be listed here.

Abstract

Given the global burden of tuberculosis, shortened treatment regimens with existing or repurposed drugs are needed to contribute to tuberculosis control. The long duration of treatment of drug-susceptible tuberculosis (DS-TB) is associated with nonadherence and loss to follow up, and the treatment success rate of multidrug-resistant tuberculosis (MDR-TB) is low (approximately 50%) with longer regimens. In this review article, we report recent advances and ongoing clinical trials aimed at shortening regimens for DS-TB and MDR-TB. We discuss the role of high-dose rifampin, as well as that of clofazimine and linezolid in regimens for DS-TB. There are at least 5 ongoing clinical trials and 17 observational studies and clinical trials evaluating shorter regimens for DS-TB and MDR-TB, respectively. We also report the results of observational studies and clinical trials evaluating a standardized nine-month moxifloxacin-based regimen for MDR-TB. Further studies, especially randomized clinical trials, are needed to evaluate regimens including newer drugs, drugs proven to be or highly likely to be efficacious, and all-oral drugs in an effort to eliminate the need for injectable drugs.

Citing Articles

Bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) for multidrug- or rifampin-resistant tuberculosis: a systematic review.

Silva D, Fernandes F, Ferreira J, Bernando W, Dalcolmo M, Dockhorn Costa Johansen F J Bras Pneumol. 2025; 50(6):e20240295.

PMID: 39813501 PMC: 11665299. DOI: 10.36416/1806-3756/e20240295.

The role and value of counsellors in the treatment journeys of people with tuberculosis and their families: Qualitative insights from the South Fly District of Papua New Guinea.

Jops P, Cowan J, Nake Trumb R, Kupul M, Kuma A, Bell S PLOS Glob Public Health. 2024; 4(10):e0002572.

PMID: 39432474 PMC: 11493273. DOI: 10.1371/journal.pgph.0002572.

Efficacy and safety of shorter multidrug-resistant or rifampicin-resistant tuberculosis regimens: a network meta-analysis.

Abraham Y, Assefa D, Hailemariam T, Gebrie D, Debela D, Geleta S BMC Infect Dis. 2024; 24(1):1087.

PMID: 39354416 PMC: 11443784. DOI: 10.1186/s12879-024-09960-3.

A Comprehensive Review on Long vs. Short Regimens in Multidrug-Resistant Tuberculosis (MDR-TB) Under Programmatic Management of Drug-Resistant Tuberculosis (PMDT).

Karnan A, Jadhav U, Ghewade B, Ledwani A, Shivashankar P Cureus. 2024; 16(1):e52706.

PMID: 38384625 PMC: 10879947. DOI: 10.7759/cureus.52706.

Early Microbiologic Markers of Pulmonary Tuberculosis Treatment Outcomes.

Paradkar M, Pradhan N, Balaji S, Gaikwad S, Chavan A, Dharmashale S Ann Am Thorac Soc. 2023; 20(12):1760-1768.

PMID: 38038600 PMC: 10704230. DOI: 10.1513/AnnalsATS.202302-144OC.

References

Ammerman N, Swanson R, Bautista E, Almeida D, Saini V, Omansen T . Impact of Clofazimine Dosing on Treatment Shortening of the First-Line Regimen in a Mouse Model of Tuberculosis. Antimicrob Agents Chemother. 2018; 62(7). PMC: 6021677. DOI: 10.1128/AAC.00636-18. View

Moodley R, Godec T . Short-course treatment for multidrug-resistant tuberculosis: the STREAM trials. Eur Respir Rev. 2016; 25(139):29-35. PMC: 9487666. DOI: 10.1183/16000617.0080-2015. View

Yew W, Chan D, Chang K . Does linezolid have a role in shortening treatment of tuberculosis?. Clin Microbiol Infect. 2019; 25(9):1060-1062. DOI: 10.1016/j.cmi.2019.06.020. View

Peloquin C . What is the 'right' dose of rifampin?. Int J Tuberc Lung Dis. 2003; 7(1):3-5. View

Job C, Yoder L, Jacobson R, Hastings R . Skin pigmentation from clofazimine therapy in leprosy patients: a reappraisal. J Am Acad Dermatol. 1990; 23(2 Pt 1):236-41. DOI: 10.1016/0190-9622(90)70204-u. View

Sotgiu G, Centis R, DAmbrosio L, Alffenaar J, Anger H, Caminero J . Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: systematic review and meta-analysis. Eur Respir J. 2012; 40(6):1430-42. DOI: 10.1183/09031936.00022912. View

Swanson R, Adamson J, Moodley C, Ngcobo B, Ammerman N, Dorasamy A . Pharmacokinetics and pharmacodynamics of clofazimine in a mouse model of tuberculosis. Antimicrob Agents Chemother. 2015; 59(6):3042-51. PMC: 4432183. DOI: 10.1128/AAC.00260-15. View

Nunn A, Phillips P, Meredith S, Chiang C, Conradie F, Dalai D . A Trial of a Shorter Regimen for Rifampin-Resistant Tuberculosis. N Engl J Med. 2019; 380(13):1201-1213. DOI: 10.1056/NEJMoa1811867. View

Grosset J, Tyagi S, Almeida D, Converse P, Li S, Ammerman N . Assessment of clofazimine activity in a second-line regimen for tuberculosis in mice. Am J Respir Crit Care Med. 2013; 188(5):608-12. PMC: 3827279. DOI: 10.1164/rccm.201304-0753OC. View

10.

Velasquez G, Brooks M, Coit J, Pertinez H, Vasquez D, Garavito E . Efficacy and Safety of High-Dose Rifampin in Pulmonary Tuberculosis. A Randomized Controlled Trial. Am J Respir Crit Care Med. 2018; 198(5):657-666. PMC: 6118011. DOI: 10.1164/rccm.201712-2524OC. View

11.

Trebucq A, Schwoebel V, Kashongwe Z, Bakayoko A, Kuaban C, Noeske J . Treatment outcome with a short multidrug-resistant tuberculosis regimen in nine African countries. Int J Tuberc Lung Dis. 2017; 22(1):17-25. DOI: 10.5588/ijtld.17.0498. View

12.

Aung K, Van Deun A, Declercq E, Sarker M, Das P, Hossain M . Successful '9-month Bangladesh regimen' for multidrug-resistant tuberculosis among over 500 consecutive patients. Int J Tuberc Lung Dis. 2014; 18(10):1180-7. DOI: 10.5588/ijtld.14.0100. View

13.

Piubello A, Harouna S, Souleymane M, Boukary I, Morou S, Daouda M . High cure rate with standardised short-course multidrug-resistant tuberculosis treatment in Niger: no relapses. Int J Tuberc Lung Dis. 2014; 18(10):1188-94. DOI: 10.5588/ijtld.13.0075. View

14.

Tang S, Yao L, Hao X, Liu Y, Zeng L, Liu G . Clofazimine for the treatment of multidrug-resistant tuberculosis: prospective, multicenter, randomized controlled study in China. Clin Infect Dis. 2015; 60(9):1361-7. DOI: 10.1093/cid/civ027. View

15.

Borisov S, Danila E, Maryandyshev A, Dalcolmo M, Miliauskas S, Kuksa L . Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report. Eur Respir J. 2019; 54(6). DOI: 10.1183/13993003.01522-2019. View

16.

Nahid P, Mase S, Migliori G, Sotgiu G, Bothamley G, Brozek J . Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline. Am J Respir Crit Care Med. 2019; 200(10):e93-e142. PMC: 6857485. DOI: 10.1164/rccm.201909-1874ST. View

17.

Nunn A, Rusen I, Van Deun A, Torrea G, Phillips P, Chiang C . Evaluation of a standardized treatment regimen of anti-tuberculosis drugs for patients with multi-drug-resistant tuberculosis (STREAM): study protocol for a randomized controlled trial. Trials. 2014; 15:353. PMC: 4164715. DOI: 10.1186/1745-6215-15-353. View

18.

Rusen I, Chiang C . Building the evidence base for shortened MDR-TB treatment regimens. Int J Tuberc Lung Dis. 2018; 22(1):1-2. DOI: 10.5588/ijtld.17.0776. View

19.

Borisov S, Dheda K, Enwerem M, Romero Leyet R, DAmbrosio L, Centis R . Effectiveness and safety of bedaquiline-containing regimens in the treatment of MDR- and XDR-TB: a multicentre study. Eur Respir J. 2017; 49(5). DOI: 10.1183/13993003.00387-2017. View

20.

Svensson E, Svensson R, Te Brake L, Boeree M, Heinrich N, Konsten S . The Potential for Treatment Shortening With Higher Rifampicin Doses: Relating Drug Exposure to Treatment Response in Patients With Pulmonary Tuberculosis. Clin Infect Dis. 2018; 67(1):34-41. PMC: 6005123. DOI: 10.1093/cid/ciy026. View