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With regard to HIV infection, a specific recommendation was made in 2011 on the use of ART in all patients with HIV and DR-TB (68, 115):
6.1. ART is recommended for all patients with HIV and drug-resistant TB requiring second-line anti-tuberculosis drugs irrespective of CD4 cell count, as early as possible (within the first 8 weeks) following initiation of anti-tuberculosis treatment (Strong recommendation, very low quality of evidence)
Corticosteroids have been used to support the treatment of serious and severe consequences of TB, such as miliary TB, respiratory insufficiency, CNS involvement and pericarditis.
The WHO Guidelines for treatment of drug-susceptible TB and patient care, 2017 update made the following recommendations (2, 130):
Surgery has been employed in the treatment of TB since before the advent of chemotherapy. With the challenging prospect that more cases of MDR/XDR-TB are virtually untreatable with all available drugs or risk having serious sequelae, there has been re-evaluation of the role of pulmonary surgery as a way to reduce the amount of lung tissue with intractable pathology and to reduce the bacterial load. Large case series have reported that resection surgery may be safe and an effective adjunct when skilled thoracic surgeons and excellent postoperative care are available (127, 128).
The clinical monitoring of patients on Hr-TB treatment follows similar principles to those that apply to other first-line TB regimens. Bacteriological monitoring of sputum generally follows the same schedule as DS-TB, with direct microscopy at months 2, 5 and 6. It is desirable, however, to perform a culture together with smear microscopy (or at least in the last month of treatment) to check for any emergent resistance, especially to rifampicin. Non-response to treatment should be investigated with DST.
The regimens recommended for treatment of Hr-TB is not divided into an intensive and a continuation phase – this simplifies the delivery and monitoring of treatment. Treatment is given daily, and intermittent treatment should be avoided. Relevant measures to support adherence, social support and the use of digital technologies should be considered to ensure favourable treatment outcomes (19).
The duration of Hr-TB treatment is driven by the need to complete 6 months of a fluoroquinolonecontaining regimen. This implies that, when Hr-TB is diagnosed after the start of the regimen for treatment of DS-TB, the companion medicines (HRZE) would end up being given for more than 6 months.
The Hr-TB regimen is recommended once isoniazid resistance has been confirmed and rifampicin resistance excluded. Rifampicin resistance needs to be excluded using rapid molecular tests (e.g. Xpert MTB/RIF) before levofloxacin is used, to avoid the inadvertent treatment of MDR/RR-TB with an inadequate regimen. Ideally, rapid DST for fluoroquinolones and pyrazinamide is also performed.
This section refers to an Hr-TB treatment regimen that has a duration of 6 months and uses oral agents.
WHO released its first evidence-based guidance for the treatment of Hr-TB using the GRADE approach in 2018 (1). The guidance is based on these two recommendations:
aDSM
active tuberculosis drug safety monitoring and management
AIDS
acquired immunodeficiency syndrome
aOR
adjusted odds ratio
ART
antiretroviral therapy