ReacciónTuberculosis (TB) strains that are resistant to TB medicines are more difficult to treat than drugsusceptible ones, and present a major challenge for patients, health care workers and health care services. In addition, the increase of drug-resistant TB (DR-TB) threatens global progress towards the targets set by the End TB Strategy (1) of the World Health Organization (WHO). Thus, there is a critical need for the continual development of evidence-based policy recommendations on the treatment and care of patients with DR-TB, based on the most recent and comprehensive evidence available.
In the past decade, WHO has developed and issued evidence-based policy recommendations for the treatment and care of patients with DR-TB, published in a range of documents (see Box 1). WHO has recently started to consolidate guidelines, in response to requests from Member States, to facilitate policy transfer at the country level. The first integrated recommendations for the management and care of multidrug- or rifampicin-resistant TB (MDR/RR-TB) were released in 2019, as the WHO consolidated guidelines on drug-resistant tuberculosis treatment (2) with an update released in 2022 (3). The consolidation of WHO recommendations on TB and DR-TB has been expanded to better outline the path that a patient will take following exposure to resistant strains of Mycobacterium tuberculosis, once infection has progressed to TB disease, and the patient has been identified by the health system and referred for DR-TB treatment.
The guidance provided in this chapter outlines specific WHO recommendations on the overall treatment management, care and monitoring of patients with MDR/RR-TB. It brings forward recommendations developed by various Guideline Development Groups (GDGs) convened by WHO. The GDGs use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to summarize the evidence, and formulate policy recommendations and accompanying remarks. This chapter incorporates recommendations that were made in 2022, based on new evidence that was available to WHO on the following: the use of the bedaquiline, pretomanid,¹⁸ linezolid and moxifloxacin (BPaLM) regimen for patients with MDR/RR-TB, and the use of 9-month all-oral bedaquiline-containing regimens for patients with MDR/RR-TB. It also includes new recommendations developed in June 2024 based on new evidence from the BEAT Tuberculosis (BEAT-TB) and endTB trials. The inclusion of new recommendations in the current update of the consolidated guidelines was communicated to the public via a rapid communication in August 2024 (4). This rapid communication was released in advance of updated WHO consolidated guidelines, to inform national TB programmes (NTPs) and other stakeholders of key changes in the treatment of DR-TB and to allow for rapid transition and planning at the country level.
Overall, this chapter focuses on recommendations for the use of effective treatment regimens for people with DR-TB; specifically, regimens for rifampicin-susceptible, isoniazid-resistant TB (Hr-TB), all-oral shorter regimens for MDR/RR-TB, longer regimens for MDR/RR-TB, monitoring the patient response to MDR/RR-TB treatment, starting antiretroviral therapy (ART) in patients on second-line anti-TB regimens, providing surgery for patients on MDR-TB treatment and hepatitis C and MDR/RR-TB treatment co-administration. Additionally, to inform the global community of the major gaps and research areas to be addressed and to inform the development of evidence-based recommendations, this document outlines the research priorities that will help to generate knowledge on evidence-based and attainable standards of health.
The recommendations included herein are a component of the WHO consolidated guidelines on TB and are primarily intended for use by NTPs, public health agencies, and other key constituencies involved in the planning, implementation and monitoring of activities for the programmatic management of DR-TB.
Drug-resistant tuberculosis (DR-TB) remains a significant public health challenge, impacting patients, communities, and healthcare systems profoundly. In 2023, global estimates suggest there were around 400 000 new cases of multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB), yet less than half of these cases were officially reported and began treatment (5). Treatment success rates have improved, rising from 50% in 2012 to 68% in 2021, but still, nearly 15% of those with MDR/RR-TB succumb to the disease (6). Before 2022, treatment options for MDR/RR-TB were suboptimal, involving prolonged treatment durations, a higher number of pills, and drugs with more severe side effects, leading to significant adverse events and less favorable outcomes. However, a breakthrough came in 2022 with the introduction of the first 6-month treatment regimen using three or four medications.
This current chapter concerns TB treatment and care; it presents WHO recommendations that have been newly developed and are published here for the first time, and existing recommendations that have been published in other WHO guidelines that applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
18 Pretomanid is a new chemical entity and a member of a class of compounds known as nitroimidazo-oxazines, which possess significant anti-TB activity and a unique mechanism of action.