Original Post on: https://www.infectiousdiseaseadvisor.com/
By: Benjamin Patterson, MBBS, Infectious Diseases Specialist

As tuberculosis (TB) is the world’s most lethal infectious disease, there is an urgent need to improve the treatment of this bacterial infection. One approach under consideration is the institution of a universal or “pan-TB” regimen comprising new agents capable of treating multidrug-resistant (MDR) and even extensively drug-resistant (XDR) TB.

The World Health Organization (WHO) target regimen profile for a pan-TB regimen aims to revolutionize the treatment of TB regardless of drug resistance.

The wish list of attributes includes a highly effective, safe, well-tolerated, 3- to 4-drug, once-daily, oral regimen with minimal drug-drug interactions that could be administered to any patient with TB regardless of age, HIV status, pregnancy status, or comorbidity.

Crucially there needs to be no or minimal pre-existing resistance for the regimen, which would allow empirical use without the need for drug susceptibility testing (DST) and therefore eliminating the delay before starting effective treatment.1

The Lancet Respiratory Medicine in April 2018 staged a debate between proponents and opponents of pan-TB regimens to address the current suboptimal worldwide management of TB resistance.

Proposing this approach, Wallis and colleagues2 argue that delayed or missed diagnosis of MDR/XDR TB in many high-burden countries leads frequently to suboptimal or ineffective treatment. Consequently, mortality and onward transmission of resistant isolates are greater than could occur with newer combinations of antimicrobial agents. In support, they cite preliminary data from the Nix-TB trial (ClinicalTrials.gov Identifier: NCT02333799); combining linezolid, pretomanid, and bedaqualine for 6 months demonstrated efficacy in patients with pre-XDR and XDR TB. Moreover, by adapting a TB transmission modelto incorporate the Nix-TB regimen, they anticipate the prevention of 4 million infections and avoiding the loss of half a million lives over the course of a decade in 4 countries with a high burden of TB: South Africa, Mozambique, India, and China (unpublished data).

Opposing this approach, Dheda and colleagues3 raise the concern that such a regimen could rapidly lead to resistance amplification and circulation of strains that are no longer susceptible to new agents in the “universal” regimen. This could lead to greatly diminished options for rescue regimens. As a result, the imagined benefits in terms of lives saved and reduction in transmission would not occur and would instead be overcome by the same barriers faced by current treatment programs (drug costs, import restrictions, inadequate scale-up of field staff, etc). Furthermore, they fear that there would be a market reaction against development of new diagnostics and new drugs, with harmful long-term consequences.

Infectious Disease Advisor discussed the differing points of view with an author of each of the opposing articles: Robert Wallis, MD, Chief Scientific Officer of the Aurum Institute, and Jennifer Furin, MD, PhD, Infectious Disease Physician and Lecturer on Global Health and Social Medicine at Harvard Medical School.