Clinical perspectives on treatment of rifampicin-resistant/multidrug-resistant TB.

Rapid diagnostics, newer drugs, repurposed medications, and shorter regimens have radically altered the landscape for treating rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB). There are multiple ongoing clinical trials aiming to build a robust evidence base to guide RR/MDR-TB treatment, and both observational studies and programmatic data have contributed to advancing the treatment field. In December 2019, the WHO issued their second 'Rapid Communication´ related to RR-TB management. This reiterated their prior recommendation that a majority of people with RR/MDR-TB receive all-oral treatment regimens, and now allow for specific shorter duration regimens to be used programmatically as well. Many TB programs need clinical advice as they seek to roll out such regimens in their specific setting. In this Perspective, we highlight our early experiences and lessons learned from working with National TB Programs, adult and pediatric clinicians and civil society, in optimizing treatment of RR/MDR-TB, using shorter, highly-effective, oral regimens for the majority of people with RR/MDR-TB.

Successful implementation of bedaquiline for multidrug-resistant TB treatment in remote Papua New Guinea.

SETTING: Bedaquiline (BDQ) was introduced in the multi-drug-resistant tuberculosis (MDR-TB) programme in Daru in remote Papua New Guinea in 2015, along with a core package of active drug-safety monitoring (aDSM). OBJECTIVE: To assess interim results and safety of BDQ for the treatment of MDR-TB from 1 July 2015 to 31 December 2017. DESIGN: A retrospective cohort analysis of routine programme data. RESULTS: Of 277 MDR-TB patients, 77 (39%) received BDQ with a total of 8 serious adverse events including 5 (6.5%) deaths, of which 1 (1.3% QTcF prolongation, grade 3) was attributable to BDQ. Of 200 (61%) patients who did not receive BDQ, there were 17 (9%) deaths. Completeness of monitoring for the BDQ group was 90% for >5 electrocardiograms and 79% for ⩾2 cultures. In the interim result indicator analysis at month 6 in the BDQ and non-BDQ groups, there were respectively 0% and 1% lost to follow-up; 6.5% and 8.5% who died; 94% and 91% in care; and 92% and 96% with negative culture among those monitored. CONCLUSION: Early experience in Daru shows BDQ is safe and feasible to implement with aDSM with good interim effectiveness supporting the rapid adoption and scale-up of the 2019 WHO MDR-TB treatment guidelines in the programme and in similar remote settings.

A bitter pill to swallow: the need for better medications for drug-resistant tuberculosis in children.

The large and growing access gap between the number of children who become sick with drug-resistant tuberculosis (DR-TB) and those who are treated for the disease each year represents a significant health systems failure. While there are multiple reasons why children with DR-TB are not diagnosed and treated, a serious challenge is the medications used to treat the disease. This paper presents three child DR-TB cases who were treated incorrectly; the cases are used to illustrate some of the problems with existing second-line medications. Challenges, including the perception that the drugs are more dangerous than the disease, lack of proper dosing recommendations and formulations, and the high cost of current treatment, all contribute to a perverse situation in which the most vulnerable pediatric patients are provided with a lower standard of care. This situation can be reversed with novel partnerships and training models, pharmacokinetic studies of the relevant drugs, increased collaboration, and dedicated funding, grounded in a rights-based approach to DR-TB in children.