The Changing Face of Multidrug-resistant Tuberculosis Treatment: From Two-year Ordeals to Six-month Cures

The injectable agents at the center of this regimenkanamycin, amikacin, and capreomycin-were aminoglycosides and polypeptides that, while bactericidal, carried a heavy toxic burden: permanent, irreversible sensorineural hearing loss developed in as many as 30% of patients, and nephrotoxicity was common.These were paired with a cocktail of older oral agents-cycloserine, ethionamide, and para-aminosalicylic acid-that brought their own burden of nausea, hepatotoxicity, and psychiatric effects, including depression and, occasionally, psychosis.The consequences of this regimen's toxicity and length were predictable: many patients simply could not finish the course they had started.Part of the problem was that the regimen itself rested on a thin evidence base-it had been assembled largely from expert consensus and small observational cohorts, long before any randomized trial had tested it head-to-head against an alternative.2 Unsurprisingly, global treatment success rates for MDR-TB hovered around only 50% through the early 2010s. 1 IntroductIon Multidrug-resistant tuberculosis (MDR-TB)-a disease caused byMycobacterium tuberculosis strains resistant to at least isoniazid and rifampicin, the two most potent first-line agents-has long stood as one of the most difficult diagnoses in infectious disease medicine.In 2024 alone, an estimated 390,000 people worldwide developed multidrug-or rifampicin-resistant TB (MDR/RR-TB), yet only 42% of them were ever diagnosed and started on treatment.1 For those who were treated, the experience has, for most of the modern antibiotic era, been arduous: years of daily pills and injections, lifealtering side effects, and-even under the best circumstances-no guarantee of cure.That picture has changed dramatically in the last decade.What was once an 18-to-24-month ordeal built around toxic injectable drugs has been compressed, for most patients, into a 6-month course of tablets.This review traces that transformation chronologically, from the injectable-based regimens that defined MDR-TB care before 2016, through the shorter regimens and the alloral revolution led by bedaquiline, to the bedaquiline-pretomanidlinezolid-moxifloxacin (BPaLM) regimen that became the global standard of care in 2022, and finally to the newest generation of 6-and 9-month regimens endorsed by WHO in 2024 and 2025.It closes with a look at the drug-development pipeline that may, within the next decade, deliver a single "pan-TB" regimen capable of treating any strain of tuberculosis regardless of its resistance profile. the Pre-2016 Standard: an 18-to-24-Month endurance teStBefore 2016, the WHO-recommended regimen for MDR-TB lasted 18 to 24 months and could require a patient to take upward of 14,000 individual pills over the full course of treatment.Worse, the first 6-8 months-the so-called intensive phase-mandated daily, painful intramuscular injections.