Tuberculosis remains the world’s most deadly infectious disease. In 2023, 10.8 million people were infected with TB, of whom 1.3 million died. Challenges to global control included drug-resistant strains and long, toxic treatment courses. Fortunately, the latest advancements offer shorter, safer, and orally administered treatments that can save millions of lives and end this epidemic.
Tuberculosis treatment has been complicated for years due to long antibiotic courses, the undesirable side effects of the medications used, and increasing resistance. The standard regimen is quite long, and for an active infection, it can last for more than six months. The biggest challenge has been multi-drug-resistant tuberculosis (MDR-TB) strains, which are particularly difficult to treat.
New-generation medications and treatment regimens (combining new compounds with existing drugs) have confirmed that it is possible to implement effective, relatively short-term therapies. Research shows that such a regimen cures TB and, at the same time, minimizes toxicity, significantly improving both clinical outcomes and quality of life.
Old Medications with a New Purpose
Bedaquiline is used as a primary treatment for rifampicin-resistant TB because it inhibits bacterial ATP synthase. However, its efficacy is at risk due to resistance (linked to prior treatment with clofazimine), so its use requires strict control.
Delamanid and Pretomanid, which are nitroimidazole derivatives, damage the mycobacterial cell wall and inhibit energy production. Although these medications were initially expensive, recent price reductions and positive safety data are contributing to their wider adoption.
These medications have led to the creation of new, potent combinations (BPaLM and BPaL) that have shortened the duration of therapy and improved the safety profile compared to previous standard regimens.
The Next Phase: Tuberculosis Treatments in Research
TBAJ-876 and Sudapiridine (WX-081): These diarylquinolines were developed to increase effectiveness and safety. Their goal is to overcome bedaquiline resistance and reduce cardiac risks.
DprE1 Inhibitors: These inhibit enzymes essential for the synthesis of the bacterial cell wall. Research is promising, but caution is needed as they share resistance mechanisms similar to bedaquiline.
GSK-656 (Gabfeborol), a benzoxaborole-type drug, works by inhibiting protein synthesis in TB bacteria. It is notable for its dose-dependent effect and good tissue penetration capacity, and it is being tested in new combination regimens.
Telacebec (Q203) disrupts bacterial respiration and is promising for the treatment of TB and other mycobacterial diseases (e.g., leprosy, Buruli ulcer).
New Oxazolidinones (Delpazolid, Sutezolid, Contezolid) aim to maintain the effectiveness of linezolid against TB but with a better safety profile. Some regimens involving these drugs reduce treatment duration and side effects.
Potential for Repurposing: Linezolid, Clofazimine, and Other Medications
Linezolid revolutionized the treatment of resistant TB, but its use is complicated by serious side effects. Research is currently underway on new dosing strategies and alternatives to maximize benefits and minimize harm.
Clofazimine: An old drug now used in short-course regimens for MDR-TB, despite a common side effect (skin discoloration).
Ethionamide and Alpibectir (a new enhancer): This combination has shown better efficacy and lower toxicity in the early stages.
Fluoroquinolones (Moxifloxacin, Levofloxacin): They maintain a significant role, and studies of their optimal use continue.
Carbapenems (Meropenem): A good choice for treating resistant strains, but their use is complicated by the need for intravenous administration.
High-Dose Rifampicin/Rifapentine: Research is underway to specify the dosing, but the results are mixed at this stage.
These advancements are moving TB treatment from a universal approach to precision medicine. New data reveals that the diversity of TB is due to individual immune characteristics and bacterial factors. Therefore, future therapy will be personalized, taking into account the patient’s condition, immune status, and biomarkers of reactivity.
Clinical trials (such as TBTC, UNITE4TB, and SMART4TB) are accelerating this progress, allowing multiple drugs and combinations to be tested simultaneously and effectively on a global scale.
Scientific breakthroughs alone are not enough to defeat TB. Equal access to new drugs, strengthened healthcare systems, personalized patient support, and better diagnostics are essential. These factors are crucial for converting progress into real outcomes, especially in the most affected regions.
Source: Lippincott
