Any patient – child or adult – with MDR/RR-TB is eligible for treatment with either a shorter all-oral bedaquiline-containing MDR-TB regimen or, if this cannot be used, a longer MDR-TB regimen (1)
Given the conditionality of the recommendation for the use of the shorter all-oral bedaquilinecontaining MDR-TB regimen, the health care provider and patient may agree to use a longer treatment regimen if the patient is eligible for the shorter all-oral bedaquiline-containing MDR-TB regimen based on that person’s individual circumstances. If the shorter all-oral bedaquiline-containing MDR-TB regimen cannot be used, the patient needs to be reassessed, with a view to starting a longer MDR-TB regimen. A patient started on the shorter all-oral bedaquiline-containing MDR-TB regimen can later be transferred to a longer MDR-TB regimen, should the need arise. However, once a patient is placed on a longer MDR-TB regimen for at least 4 weeks, normally that patient can no longer be switched to the shorter all-oral bedaquiline-containing MDR-TB regimen because this 4-weeks treatment would represent an exposure to second-line medicines.
MDR/RR-TB alone or with additional resistance: Both shorter and longer regimens are more likely to be effective if the composition is guided by reliable DST. If rifampicin resistance is detected, rapid molecular tests for resistance to isoniazid and fluoroquinolones should be performed promptly, to inform the decision about which medicines to use for the treatment of MDR/RR-TB. Ideally, all MDR/ RR-TB patients are tested for resistance to fluoroquinolones as a minimum before starting MDR-TB treatment. DST can be performed for anti-TB medicines for which there are now agreed reliable and reproducible methods (e.g. bedaquiline, linezolid, clofazimine, delamanid and pyrazinamide). Phenotypic DST for ethambutol, cycloserine/terizidone, imipenem/meropenem, ethionamid/ prothionamid and p-aminosalicylic acid is not reliable and is not routinely recommended. Hence, other approaches may be needed, to determine the likelihood of effectiveness of selected medicines. If one or more agents are unlikely to be effective, then they need to be replaced (or, if they are included in the regimen, not counted as effective) in order to have at least four effective agents to start with. The design of longer regimens for MDR-TB with additional resistance to fluoroquinolones or other second-line drugs follows a similar logic to that used for other MDR-TB patients. The capacity for DST for new and repurposed second-line drugs may not be available in all national reference laboratories, but it is imperative that this capacity is established as soon as possible (16, 17).
Rifampicin-resistant TB: Any patient with rifampicin-resistant TB – whether a child or an adult – in whom isoniazid resistance is absent or unknown, needs to be treated with a recommended MDR-TB regimen. The regimen could be a shorter all-oral bedaquiline-containing regimen or a longer MDR-TB regimen if the former cannot be used. High-dose isoniazid has also been shown to be an important component in paediatric regimens (15). Although high-dose isoniazid is not included in Groups A–C, it may still be used in patients with confirmed susceptibility, or in the presence of mutations that do not usually confer complete resistance to isoniazid.