Treatment of tuberculosis

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Treatment of Drug-Susceptible TB (DS-TB)

For the past 50 years, DS-TB has been treated with the 'short-course chemotherapy' regimen, which includes an ‘intensive’ phase of 2 months of rifampicin, isoniazid, and pyrazinamide, followed by a ‘continuation’ phase of 4 months with rifampicin and isoniazid. This approach has been effective in curing most patients. Rifapentine, a rifamycin with a longer half-life, combined with isoniazid, pyrazinamide, and moxifloxacin, has been shown to reduce therapy duration to 4 months. In May 2022, the WHO conditionally recommended this 4-month regimen for eligible individuals aged 12 and older with pulmonary DS-TB.

Treatment of Isoniazid-Resistant, Rifampicin-Susceptible TB

Isoniazid resistance without concurrent rifampicin resistance is the most common form of Mycobacterium tuberculosis resistance globally, affecting an estimated 10.6% of all TB cases in 2019. In 2018, WHO recommended a regimen of 6 months of rifampicin, ethambutol, pyrazinamide, and levofloxacin to treat isoniazid-resistant TB. This recommendation was conditional and based on very low certainty of evidence. For cases of noncavitary disease, low bacillary burden, or pyrazinamide toxicity, European-American guidelines suggest administering pyrazinamide only during the first 2 months, provided a later-generation fluoroquinolone is used. Patients with fluoroquinolone resistance or contraindications are generally recommended a 6-month regimen of rifampicin, ethambutol, and pyrazinamide, although these latter recommendations lack clinical trial evidence and rely on expert opinion.

Treatment of Multidrug-Resistant and Rifampicin-Resistant TB (MDR/RR-TB)

Management recommendations for MDR/RR-TB have shifted from 18–20 months of treatment to an all-oral, shorter 9–12 month regimen in which bedaquiline replaces kanamycin. In 2022, WHO recommended this shorter regimen with bedaquiline (and the option to replace ethionamide with linezolid for 2 months) for MDR/RR-TB without fluoroquinolone resistance. Additionally, a regimen of bedaquiline, linezolid, pretomanid, and moxifloxacin (BPaLM) was conditionally recommended for fluoroquinolone-susceptible MDR/RR-TB, though the supporting evidence is of very low certainty.

Treatment of MDR/RR-TB with Fluoroquinolone Resistance

For cases with proven fluoroquinolone resistance, WHO recommends the BPaL regimen, though this recommendation is based on very low certainty of evidence. The optimal dosage of linezolid remains uncertain; current WHO guidelines suggest 600 mg daily, but the evidence for this dose is limited. Research suggests a feasible 6–9 month, 3–4 drug regimen to treat fluoroquinolone-resistant MDR/RR-TB, and a four-drug regimen (e.g., bedaquiline, linezolid, delamanid, and clofazimine) or extended treatment duration may be warranted in cases with multiple poor prognostic features.

Future Research Priorities

There is a critical need to develop well-tolerated, safe, and shorter regimens for both DS-TB and drug-resistant TB (DR-TB). Particular emphasis should be placed on identifying an alternative to linezolid with fewer adverse effects. Efficiently testing new regimens will require the identification of reliable biomarkers to serve as surrogates for relapse-free cure.


Source:
Motta, I., Boeree, M., Chesov, D., Dheda, K., Günther, G., Horsburgh Jr, C.R., Kherabi, Y., Lange, C., Lienhardt, C., McIlleron, H.M. and Paton, N.I., 2024. Recent advances in the treatment of tuberculosis. Clinical Microbiology and Infection, 30(9), pp.1107-1114.

 

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