Evaluation of Effectiveness and Safety of a New Short-Course Chemotherapy Regimen for Drug-Susceptible Tuberculosis
https://doi.org/10.58838/2075-1230-2025-103-6-8-16
Abstract
The objective: to compare effectiveness and safety of treatment of drug-susceptible tuberculosis when using four-month and six-month chemotherapy regimens.
Subjects and Methods. A multicenter cohort study was conducted from October 2023 to August 2025 to study treatment of drug-susceptible tuberculosis using a short-course (four-month) regimen (SC Group) of chemotherapy (CT) compiled of the following agents: rifapentine (900 mg daily), isoniazid, pyrazinamide, and levofloxacin in the intensive phase for two months and rifapentine (900 mg daily), isoniazid, and pyrazinamide in the continuation phase. Comparison Group (CG) included patients who received a six-month chemotherapy regimen for drug-susceptible tuberculosis during the same period. Effectiveness was assessed by sputum conversion and clinical and radiological changes.
Results. Effective treatment was achieved in 92.0% (46/50) of patients in Short-Course Regimen Group versus 76.6% (46/60) in Comparison Group (p = 0.038). Sputum conversion by smear according to microscopy data by the end of therapy was registered in 96.0% (48/50) and 76.7% (46/60), respectively (p = 0.005); and sputum conversion by culture was reported in 94.0% (47/50) and 73.3% (44/60) (p = 0.004). The overall frequency of adverse reactions was significantly lower in the Short-Course Regimen Group (57.7% vs. 74.6%; p = 0.045).
About the Authors
V. V. TestovRussian Federation
Vadim V. Testov - Candidate of Medical Sciences,
Deputy Director for Statistics and Reporting
Build. 2, 4 Dostoevskiy St., Moscow, 127473
Phone: +7 (495) 631-15-15
I. A. Vasilyeva
Russian Federation
Irina A. Vasilyeva - Doctor of Medical Sciences, Professor, Director, Head of Phthisiology Department, Clinical Medicine Institute
Build. 2, 4 Dostoevskiy St., Moscow, 127473
Phone: +7 (495) 631-15-15
V. A. Guseva
Russian Federation
Valeriya A. Guseva - Head of Telemedicine Center
Build. 2, 4 Dostoevskiy St., Moscow, 127473
Phone: +7 (495) 631-15-15
V. N. Zimina
Russian Federation
Vera N. Zimina - Doctor of Medical Sciences, Leading Researcher of Infectious Diseases Department, Professor of Phthisiology Department
Build. 2, 4 Dostoevskiy St., Moscow, 127473
Phone: +7 (495) 631-15-15
N. A. Stepanova
Russian Federation
Natalya A. Stepanova - Doctor of Medical Sciences,
Professor of Phthisiology Department, Phthisiologist,
Regional Clinical TB Dispensary
121 Bakinskaya St., Astrakhan, 414000
Phone: +7 (8512) 66-94-80
A. V. Nesterenko
Russian Federation
Anna V. Nesterenko - Candidate of Medical Sciences,
Phthisiologist, Head Physician
26, 60 let Oktyabrya St., Krasnoyarsk, 660078
N. A. Zubova
Russian Federation
Natalya A. Zubova - Doctor of Medical Sciences,
Deputy Head Physician on Reporting and Statistics
34 Ulyanova St., Saransk, Mordoviya Republic, 430032
M. A. Dolgova
Russian Federation
Marina A. Dolgova - Deputy Head Physician for Clinical
and Expert Activities
198, Rodionova St., Nizhny Novgorod, 603093
N. V. Rachina
Russian Federation
Natalia V. Rachina - Candidate of Medical Sciences, Head Physician
Village of Schetinka, Kursky Raion, Kursk Region, 305511
Phone: + 7 (4712) 34-45-06
M. A. Andreev
Russian Federation
Mikhail A. Andreev - Deputy Head Physician for Medical Activities
4 Pirogov St., Cheboksary, the Chuvash Republic, 428015
Phone: + 7 (8352) 58-21-30
N. I. Skorovarova
Russian Federation
Natalya I. Skorovarova - Deputy Head Physician
for Medical Activities
6 Nezhinskoye Rd., Orenburg, 460008
Phone: + 7 (3532) 37-85-65
References
1. Klinicheskie rekomendatsii. Tuberkulez. [Clinical guidelines. Tuberculosis]. 2024. Available: https://cr.minzdrav.gov.ru/recomend/16_2 Accessed November 1, 2025
2. Samoylova A.G., Veselova E.I., Lovacheva O.V., Kaminskiy G.D. The anti-tuberculosis antibiotic of rifapentine: perspectives of clinical use. Tuberculosis and Lung Diseases, 2018, vol. 96, no. 12, pp. 55-61. (In Russ.) https://doi.org/10.21292/2075-1230-2018-96-12-55-61
3. Bea S., Lee H., Kim J.H., Jang S.H., Son H., Kwon J.W. et al. Adherence and associated factors of treatment regimen in drug-susceptible tuberculosis patients. Front. Pharmacol., 2021, no. 12, pp. 1-9.
4. Che Y., Song Q., Yang T., Ping G., Yu M. Fluoroquinolone resistance in multidrug-resistant Mycobacterium tuberculosis independent of fluoroquinolone use. Eur. Respir. J., 2017, no. 50, pp. 1700-1708.
5. Common Terminology Criteria for Adverse Events (CTCAE) Version 5. Bethesda, M.D. National Cancer Institute, 2017. Available: https://dctd.cancer.gov/research/ctep-trials/for-sites/adverse-events/ctcae-v5-5x7.pdf Accessed September 27, 2024
6. Dooley K.E., Bliven-Sizemore E.E., Weiner M., Lu Y., Nuermberger E.L., Hubbard W.C. et al. Safety and pharmacokinetics of escalating daily doses of the antituberculosis drug rifapentine in healthy volunteers. Clin. Pharmacol. Ther., 2012, vol. 91, no. 5, pp. 881-888.
7. Dorman S.E., Goldberg S., Stout J.E., Muzanyi G., Johnson J.L., Weiner M. et al. Substitution of rifapentine for rifampin during intensive phase treatment of pulmonary tuberculosis: Study 29 of the tuberculosis trials consortium. J. Infect. Dis., 2012, vol. 206, no. 7, pp. 1030-1040.
8. Dorman S.E., Nahid P., Kurbatova E.V., Phillips P.P.J., Bryant K., Dooley K.E. et al. Four-month rifapentine regimens with or without moxifloxacin for tuberculosis. N. Engl. J. Med., 2021, vol. 384, no. 18, pp. 1705-1718.
9. Dorman S.E., Savic R.M., Goldberg S., Stout J.E., Schluger N., Muzanyi G. et al. Daily rifapentine for treatment of pulmonary tuberculosis: a randomized, dose-ranging trial. Am. J. Respir. Crit. Care Med., 2015, vol. 191, no. 3, pp. 333-343.
10. Duarte R., Munsiff S.S., Nahid P., Saukkonen J.J., Winston C.A., Abubakar I. et al. Updates on the treatment of drug-susceptible and drug-resistant tuberculosis: an official ATS/CDC/ERS/IDSA clinical practice guideline. Am. J. Respir. Crit. Care Med., 2025, no. 211, pp. 15-33.
11. Goutelle S., Bahuaud O., Genestet C., Millet A., Parant F., Dumitrescu O. et al. Exposure to rifampicin and its metabolite 25-deacetylrifampicin rapidly decreases during tuberculosis therapy. Clin. Pharmacokinet., 2025, vol. 64, no. 3, pp. 387-396.
12. Hu Y., Liu A., Ortega-Muro F., Alameda-Martin L., Mitchison D., Coates A. High-dose rifampicin kills persisters, shortens treatment duration, and reduces relapse rate in vitro and in vivo. Front. Microbiol., 2015, no. 6, pp. 1-9.
13. Louie J.K., Agraz-Lara R., Velásquez G.E., Phillips A., Szumowski J.D. Experience with four-month rifapentine and moxifloxacin-based tuberculosis treatment in San Francisco. Open Forum Infect. Dis., 2024, vol. 11, no. 4, pp. ofae178.
14. Noordzij M., Van Diepen M., Caskey F.C., Jager K.J. Relative risk versus absolute risk: one cannot be interpreted without the other. Nephrol. Dial. Transplant., 2017, vol. 32, suppl 2, pp. 13-18.
15. Peloquin C.A., Namdar R., Singleton M.D., Nix D.E. Pharmacokinetics of rifampin under fasting conditions, with food, and with antacids. Chest, 1999, vol. 115, no. 1, pp. 12-18.
16. Redfors B. A case for using relative rather than absolute noninferiority margins in clinical trials. JACC Adv., 2024, no. 3, pp. 1-8.
17. Roberts M.R., Ashrafzadeh S., Asgari M.M. Research techniques made simple: interpreting measures of association in clinical research. J. Invest. Dermatol., 2019, no. 139, pp. 502-511.
18. Rosenthal I.M., Zhang M., Williams K.N., Peloquin C.A., Tyagi S., Vernon A.A. et al. Daily dosing of rifapentine cures tuberculosis in three months or less in the murine model. PLos Med., 2007, vol. 12, no. 4, pp. e344.
19. Rusu A., Munteanu A.C., Arbănași E.M., Uivarosi V. Overview of side-effects of antibacterial fluoroquinolones: new drugs versus old drugs, a step forward in the safety profile? Pharmaceutics, 2023, no. 15, pp. 1-21.
20. Savic R.M., Weiner M., MacKenzie W.R., Engle M., Whitworth W.C., Johnson J.L. et al. Defining the optimal dose of rifapentine for pulmonary tuberculosis: exposure–response relations from two phase II clinical trials. Clin. Pharmacol. Ther., 2017, vol. 102, no. 2, pp. 321-331.
21. Shee S., Singh S., Tripathi A., Thakur C., Kumar A.T., Das M. et al. Moxifloxacin-mediated killing of Mycobacterium tuberculosis involves respiratory downshift, reductive stress, and accumulation of reactive oxygen species. Antimicrob. Agents Chemother., 2022, vol. 66, no. 9, pp. e0059222.
22. Silva D.R., Mello F.C.Q., Migliori G.B. Shortened tuberculosis treatment regimens: what is new? J. Bras. Pneumol., 2020, no. 46, pp. 1-8.
23. Wang P., Peskoe S., Byrd R., Smith P., Breslin R., Chow S.C. Statistical evaluation of absolute change versus responder analysis in clinical trials. Acta Mater Med., 2022, vol. 3, no. 1, pp. 320-332.
24. World Health Organization (WHO). WHO consolidated guidelines on tuberculosis. Module 4: Treatment – Drug-susceptible tuberculosis treatment. Geneva, WHO Press, 2022.
25. World Health Organization (WHO). Global tuberculosis report. Geneva, WHO Press, 2024.
Review
For citations:
Testov V.V., Vasilyeva I.A., Guseva V.A., Zimina V.N., Stepanova N.A., Nesterenko A.V., Zubova N.A., Dolgova M.A., Rachina N.V., Andreev M.A., Skorovarova N.I. Evaluation of Effectiveness and Safety of a New Short-Course Chemotherapy Regimen for Drug-Susceptible Tuberculosis. Tuberculosis and Lung Diseases. 2025;103(6):8-16. (In Russ.) https://doi.org/10.58838/2075-1230-2025-103-6-8-16




































