This article is a follow-up to “From decline to resurgence: Rise and response to US and global TB burden,” published in the February 2025 CHEST Physician® issue.
Resistance to traditional therapies for TB—isoniazid, rifampin, pyrazinamide, and ethambutol—is a significant contributor to TB treatment failure and disease progression. Globally, up to 16% of patients who received TB treatment will develop multidrug-resistant (MDR) TB, which is defined as TB that is resistant to rifampin and isoniazid.1 This equates to approximately 400,000 new cases of MDR-TB annually around the world and 100 new cases per year diagnosed in the United States.2
Unlike for patients with drug-susceptible TB, the incidence of MDR-TB has remained stable for the last several years, though the mortality rate of those with MDR-TB remains comparably higher. Prior TB infection is the greatest risk factor for MDR-TB infection.
Previously, treatment for MDR-TB consisted of an arduous 18- to 24-month regimen of five or more drugs, often including parenteral medications with serious, sometimes irreversible, toxicities. Since 2019, practitioners have successfully treated patients with MDR-TB using an abbreviated all-oral, six-month, three-drug regimen that includes bedaquiline, pretomanid, and linezolid (BPaL), or BPaLM, which includes moxifloxacin in fluoroquinolone-susceptible strains.3
Notably, bedaquiline and pretomanid are novel anti-TB agents. All-oral regimens like BPaL and others are not only shorter with improved adherence rates, but they are also more effective. Recently, Guglielmetti and colleagues demonstrated noninferiority of three other short-course bedaquiline-containing regimens for rifampin-resistant TB compared with traditional regimens.4
The appropriate selection of anti-TB therapy given the expanded treatment options can indeed be befuddling. In the United States, the Centers for Disease Control and Prevention offers next-generation molecular detection of drug resistance testing to all patients to help guide therapy. All such cases of MDR-TB should be managed in tandem with a TB infection specialist, a local public health TB program, and a TB Center of Excellence.