In settings where the 6-month MDR/RR-TB regimen is not yet available, or implementation of the regimen is not yet feasible, or for patients who are not eligible, selected patients with MDR/RR-TB may benefit from a 9-month all-oral regimen. Several eligibility criteria must be considered for this regimen, with additional considerations for the use of linezolid instead of ethionamide.
The 9-month all-oral regimen (with either ethionamide or linezolid) may be offered to the following patients with MDR/RR-TB (where resistance to at least rifampicin has been confirmed and resistance to fluoroquinolones has been ruled out):
- those with no documented resistance or suspected ineffectiveness of bedaquiline, clofazimine, or ethionamide or linezolid (whichever is considered for inclusion in the regimen);
- those with no exposure to previous treatment with bedaquiline, fluoroquinolones,4 clofazimine, or ethionamide or linezolid (whichever is considered for inclusion in the regimen) for more than 1 month – when prior drug exposure is greater than 1 month, patients may still receive this regimen if resistance to the specific medicine with such exposure has been ruled out;
- those with no extensive or severe TB disease5 and no severe extrapulmonary TB;6
- all people living with or without HIV;
- women who are pregnant or breastfeeding: these patients may be considered eligible for the linezolid-containing 9-month regimen, but they should not receive the 9-month regimen containing ethionamide; and
- children and adults without bacteriological confirmation of TB or resistance patterns but who require MDR/RR-TB treatment based on clinical signs and symptoms of TB (including radiological findings) and history of contact with someone with confirmed MDR/RR-TB: these patients may be eligible for this regimen based on the drug resistance profile of the isolate obtained from the most likely index case.
Linezolid is associated with considerable toxicity, which necessitates close monitoring for signs of bone marrow suppression and neuropathies. Optic neuritis and peripheral neuropathies tend to be reported beyond 2 months of treatment with linezolid, whereas myelosuppression is significantly dose dependent and is more likely to occur during the first 2 months of exposure to the drug (42, 43). Nevertheless, linezolid is far more effective than ethionamide and helps to maintain a relatively effective regimen, particularly in cases of MDR/RR-TB where phenotypic DST results are awaited to confirm fluoroquinolone susceptibility. Therefore, the 9-month all-oral regimen containing linezolid (instead of ethionamide) should be offered wherever possible to patients who fulfil the eligibility criteria above, as well as the following:
- serum haemoglobin above 8 g/dL, neutrophils above 0.75 × 109/L and platelets above 150 × 109/L at the start of treatment; and
- no evidence of severe peripheral neuropathy, or any sign or suspicion of optic neuritis, at the start of treatment.
The 9-month all-oral regimen with ethionamide instead of linezolid, or a longer regimen without linezolid, may be more appropriate options for patients with very low haemoglobin, neutrophils or platelets, severe peripheral neuropathy or concerns regarding vision. Mild or moderate peripheral neuropathy (Grade 1 or 2) may also be sufficient reason to offer a 9-month regimen that uses ethionamide, based on the patient’s preference after discussing the risks and benefits of not including linezolid. However, the ethionamide-containing regimen must be avoided in individuals who are pregnant or breastfeeding. The decision regarding which regimen offers the best option for cure in a patient may also depend on other considerations; for example, preferences of patients and clinicians, pill burden, drug formulations, regional DRS data, feasibility of monitoring for drug adverse effects, and availability of blood transfusion services or ophthalmology services, if required.
If the 9-month all-oral MDR/RR-TB regimen (with either linezolid or ethionamide) cannot be used, the patient must be reassessed for their eligibility for another appropriate regimen, either BPaLM/ BPaL or a longer MDR-TB regimen.
4 This includes exposure to fluoroquinolones as either treatment or prevention of MDR/RR-TB.
5 See definitions in Chapter 2.
6 See definitions in Chapter 2.