Treatment

In patients with MDR/RR-TB, there are several regimens that can be used based on current WHO policy. The key factors that define treatment regimen choice include drug-resistance profile, prior exposure to TB medicines and patient history, drug-resistance profile of close contacts, the patient’s age, extent of pulmonary TB disease and localization of extrapulmonary TB lesions.

The safety profile of some medicines used concomitantly in a long treatment regimen may present its own concerns. aDSM should be performed, as well as proper management of adverse events and prevention of complications from drug–drug interactions. The NTP should actively monitor drug safety to ensure proper patient care, to report any adverse events to the responsible drug safety authority in the country, and to inform national and global policy.

Extensive (or advanced) TB disease in adults is defined as the presence of bilateral cavitary disease or extensive parenchymal damage on chest radiography. In children aged below 15 years, extensive (or advanced) disease is usually defined by the presence of cavities or bilateral disease on chest radiography. This highlights the importance of chest radiography as part of the diagnostic work-up for patients, along with bacteriological tests. Patients with extensive disease tend to have a higher bacterial burden, especially in cases of parenchymal lung destruction (e.g.

The WHO recommendations on longer MDR-TB regimens also apply to patients with extrapulmonary disease. Adjustments may be required, depending on the specific location of disease. Treatment of MDR/RR-TB meningitis is best guided by DST of the infecting strain and by the ability of TB medicines to cross the blood–brain barrier. Group A fluoroquinolones (e.g. levofloxacin, moxifloxacin and linezolid) have good penetration across the blood–brain barrier (i.e. the CNS), as do ethionamide (or prothionamide), cycloserine (or terizidone) and imipenem–cilastatin (109–111).

Currently, there are no specific changes in using longer regimens in People with HIV. However, there can be cumulative risk factors for clinical complications, toxicities and drug–drug interactions (Web Annex 1 and Web Annex 2); hence, these patients may need close follow-up and support.

When designing these regimens, a number of basic principles need to be respected, in line with the best available evidence on composition of the regimens, as per the latest WHO guidelines (1).

The total length of a long treatment regimen is 18 to 20 months.

Three evidence-based recommendations guide the duration of the longer MDR-TB regimens:

Although the 9-month all-oral MDR/RR-TB regimen is taken for much less time than the longer regimens, this regimen still has a high pill burden and includes medications with multiple overlapping toxicities. The most common adverse events associated with the 9-month all-oral regimen are anaemia (among patients receiving the linezolid-containing regimen), hepatotoxicity, QT prolongation, nausea and vomiting (59).

Older patients