Discovered in 1882 by Robert Koch, the tubercle bacillus is the cause of human tuberculosis. Very common in African and Asian countries, this disease presents several clinical manifestations, primarily affecting the respiratory tract, and can develop into extrapulmonary forms. For several decades, antituberculosis drugs have been used, with the standard treatment consisting of a four-drug regimen (isoniazid, rifampicin, pyrazinamide, ethambutol) [1] during the initiation phase and a two-drug regimen (isoniazid, rifampicin) during the continuation phase, provided complete sensitivity has been demonstrated [2] . However, over time, strains resistant to one or more drugs have been identified. Drug-resistant tuberculosis remains a major public health problem worldwide [3] . Indeed, strains resistant to antituberculosis medications are more challenging to treat than sensitive strains, posing a significant challenge not only for National Tuberculosis Control Programs but also for the WHO’s “End TB 2030” strategy. The progressive increase in MDR-TB cases globally threatens the progress made and the targets set by the World Health Organization’s (WHO) Strategy to End Tuberculosis [3] . The Central African Republic (CAR) is among the world’s 30 high TB burden countries, with an estimated incidence of 540 cases per 100,000 population in 2022 [4] . The estimated proportion of TB cases with MDR/RR-TB was 9.1% for new cases and 46.6% for previously treated cases, with an overall incidence estimated at 8.9 cases per 100,000 population. In 2022, the country reported 122 MDR-TB cases (or 24% of expected cases), among which 108 (89%) were started on treatment. The treatment success rate for MDR/RR-TB patients who started second-line treatment in 2020 was 80%. Given the significant emergence of resistance to first-line antituberculosis drugs, low treatment success rates, and numerous adverse effects, the introduction of new antibiotics and treatment regimens is essential for controlling MDR-TB. Bedaquiline (SIRTURO®) is a diarylquinoline antimycobacterial agent with a novel mechanism of action that inhibits ATP synthase, offering bactericidal and sterilizing properties [5] . Several studies have demonstrated the efficacy of bedaquiline-based regimens in treating multidrug-resistant tuberculosis, showing better treatment outcomes, reduced mortality, and the potential to shorten treatment duration [6] . It is in this context that the CAR recommended in 2022 the use of the 9-month regimen combining Bedaquiline-Pretomanid-Linezolid-Moxifloxacin (BPaLM) for patients with MDR/RR-TB [7] . The objective of this study was to evaluate the efficacy of bedaquiline in patients with multidrug-resistant tuberculosis in the Central African Republic.

Patients. A total of 68 patients were included in the study, with ages ranging from 8 to 62 years and an average age of 32 years. The majority of the study population consisted of men (41 men and 27 women), corresponding to a male-to-female ratio of 1.5. The HIV status was known to be positive for 6 out of the 68 patients ( Table 2 ).

In the study of 68 strains, the antibiotic resistance profile showed that 9 out of 68 (13.2%) Mycobacterium tuberculosis isolates were sensitive to all the antituberculosis drugs tested. Meanwhile, 56 out of 68 (86.7%) were MDR strains, resistant to Rifampicin and Isoniazid. Three isolates were Pre-XDR strains 3 out of 68 (4.41%), resistant to rifampicin and Isoniazid in addition to fluoroquinolones such as Moxifloxacin, Ofloxacin, Levofloxacin, and Ciprofloxacin ( Table 3 ).

A total of 59 patients were put on treatment, including 56 MDR-TB patients and three Pre-XDR patients. We observed two deaths among the MDR-TB patients at the beginning of the treatment.

Regarding the follow-up of the treatment, 57 patients successfully completed their treatment with a negative culture result at the 21st month (M21).

Concerning sensitivity to bedaquiline, no mutations were found in the atpC genes ( Table 4 ).

The objective of this study was to describe the progression, bacteriological profile, and outcomes of patients with multidrug-resistant tuberculosis (MDR-TB) treated under a therapeutic protocol including bedaquiline in 2024.

The MDR-TB patients were mainly men (61.01%, 36/59) and young (aged 30 - 40 years). This predominance among men and the young may be related to their socio-professional situation, which increases their exposure to tuberculosis in general and probably to multidrug-resistant tuberculosis. These results are similar to a study conducted in the Central African Republic by (Farra et al.), where men with MDR-TB represented 66.3% [4] [13] .

Simultaneous resistance to rifampicin and isoniazid, which defines multidrug-resistant tuberculosis, was found in 82.35% of cases. These results are similar to a study conducted by Dje.bi et al. in 2023 in Bouake, which found a prevalence of 62.9% of MDR-TB and 4.42% of Pre-XDR patients [13] - [16] . We note that the proportion of MDR-TB cases has almost increased in CAR. These results are contrary to the efforts made by the WHO to reduce the emergence of resistant forms of tuberculosis, which represent a significant public health problem.

Regarding the outcomes of patients under treatment, 100% of patients on treatment had a favorable outcome (treatment completed, success of treatment, and declared cured) by the end of the short treatment established for 9 months with follow-up examinations (microscopy and culture on Löwenstein-Jensen medium) at months 10, 11, 15, and 21. These data are higher than those of Jayadeep et al., with a success rate of 88.9%. We regret two cases of death, which were unrelated to the treatment; these patients were diagnosed with MDR-TB but had not yet been started on treatment when they died, as the country had experienced a two-month medication shortage.

Here, we must highlight the key findings of the results and consider future perspectives.

Given the unmet needs of patients with multidrug-resistant tuberculosis (MDR-TB) and the significant side effects, the introduction of bedaquiline is necessary. The primary goal is to eliminate tuberculosis. According to the data from our study and other similar studies, improving the culture conversion rate and achieving favorable outcomes after the introduction of bedaquiline could offer new perspectives for effective therapeutic management of MDR-TB patients in the Central African Republic.

This study on the efficacy of bedaquiline in patients with multidrug-resistant tuberculosis treated at the MDR-TB patient care center at CNHUB, with patient follow-up through sputum culture at the NRL/TB at the Pasteur Institute of Bangui and strain sequencing, showed a success rate of 100%. Bedaquiline has proven to be a major advancement in the treatment of multidrug-resistant tuberculosis, offering a more effective therapeutic option. Inadequate use could encourage the development of resistance, highlighting the need for rigorous monitoring of patients under treatment and strengthening the genomic platform at the NRL/TB for proper follow-up and effective therapeutic management of MDR-TB patients in the Central African Republic.

We thank the staff of the diagnostic and treatment centers who referred suspected multidrug-resistant tuberculosis patients to the National Reference Laboratory for Tuberculosis at the Pasteur Institute of Bangui for diagnosis. We also thank the Global Fund to Fight AIDS, Tuberculosis, and Malaria for its support to the NRL-TB, which provided the necessary reagents free of charge for conducting the Xpert MTB/RIF test, culturing samples, and monitoring patients under treatment. Additionally, we thank the French Embassy in the Central African Republic for awarding a grant that enabled me to sequence the strains at the IHU Marseille.