Tuberculosis (TB), a chronic respiratory infection caused by Mycobacterium tuberculosis, continues to be a major public health challenge despite advances in diagnostics and therapeutics (1). One of the most urgent and obstacle to global TB control is the spreading of rifampicin-resistant TB (RR-TB) (2). Previous studies have demonstrated that rifampicin resistance in Mycobacterium tuberculosis is predominantly mediated by mutations in the rpoB gene, with additional contributions from efflux pump gene mutations in certain strains. Socioeconomic factors, particularly irregular treatment regimens, exacerbate resistance dynamics by creating selective environments that favor the proliferation of resistant strains over susceptible populations. Furthermore, the transmission of these drug-resistant strains perpetuates the spread of resistance, compounding the public health challenge (3–5). RR-TB encompasses diverse resistance patterns, including mono-resistance, multidrug resistance, and polydrug resistance to rifampicin—a cornerstone of first-line TB treatment. The development of rifampicin resistance complicates clinical management, leading to more toxic and prolonged treatment regimens, extended infectiousness, and significantly higher healthcare costs (6, 7). Thus, to meet the ambitious goal of ending TB by 2035, early detection and effective treatment of RR-TB should be a crucial component.

Globally, the annual incidence of MDR/RR-TB remained relatively stable from 2020 to 2023, with an estimated 400,000 cases (95% UI: 360,000–440,000) and approximately 150,000 deaths (95% UI: 94,000–210,000) reported in 2023. The resistance rates demonstrated significant variation between new TB cases (3.2%; 95% UI: 2.5–3.8%) and previously treated cases (16.0%; 95% UI: 9.0–24%) (1). China represents one of the high-burden countries for RR-TB, with an estimated 29,000 new RR-TB cases reported in 2023, constituting 7.3% of global cases and ranking fourth worldwide in terms of disease burden (1). Surveillance data from Fujian Province, located in southeastern China, demonstrated significantly elevated RR-TB prevalence rates during the 2016–2019 period, with resistance detected in 4.4% of new TB cases and 16.8% of previously treated cases (8). Compared with national/global averages, Fujian’s RR-TB rates in previous monitoring was relatively high. In response to this public health challenge, Fujian Province has implemented comprehensive measures to control RR-TB prevalence, including the enhancement of detection capabilities to achieve a drug resistance screening rate exceeding 90% for bacteriologically confirmed TB cases. Building upon these efforts, our study conducts a analysis of the epidemiological characteristics and treatment outcomes of RR-TB in southeastern China from 2019 to 2024. The study aims to understand the prevalence and treatment outcome of rifampicin resistance in Fujian Province, and to identify modifiable risk factors for unsuccessful treatment outcome. The finding will provide valuable insights and evidence-based recommendations for the development of more precise and effective RR-TB prevention and control strategies in the future.

In 2019, the Fujian Provincial Government launched the “Action Plan to End Tuberculosis (2019–2022)” and set ambitious targets for rifampicin resistance testing. The new goal was to screen at least 90% of bacteriologically confirmed TB cases for rifampicin resistance by 2022. Based on province-wide drug resistance screening data, this study revealed that the overall rifampicin resistance rate among culture-positive pulmonary TB cases in Fujian Province was 3.7%, showing a steady year-on-year decline. The resistance rates in both new TB cases and high-risk groups were lower than those reported nationally and in other provinces (9–13). The decline was primarily observed in new TB cases, while the resistance rate in high-risk groups remained relatively stable, indicating some success in curbing the transmission of RR-TB. Although the resistance rate in high-risk groups was significantly higher than in new patients, the absolute number of RR-TB cases was greater among new TB cases due to their substantially larger case population. Therefore, our current strategy emphasizes equal attention to both populations in prevention and screening efforts.

Geographical analysis revealed regional variations in rifampicin resistance rates, with higher rates in eastern Fujian compared to southern, northern and western regions. This disparity may be attributed to economic and demographic factors, as eastern Fujian is more economically developed, with greater population mobility and density, which increase the risk of RR-TB transmission. Additionally, studies suggest that the concentration of medical resources in economically developed areas may lead to cross-regional healthcare-seeking behavior, potentially facilitating the spread of RR-TB (14, 15).

The majority of RR-TB patients in Fujian were male, aged 45 years or older, farmers or workers, and non-local residents. These demographic characteristics may be associated with lifestyle factors (e.g., smoking, alcohol use), broader social networks, and the higher prevalence of comorbidities (e.g., diabetes, chronic obstructive pulmonary disease) in older adults, all of which may increase the risk of infection and transmission of drug-resistant strains (16, 17). However, the higher RR-TB rate among females, unemployed and retired individuals or younger individuals (<45 years) also warrant close attention. Given these findings, targeted interventions, including enhanced screening strategies, should be implemented to facilitate early detection and control of RR-TB in these groups.

The study found that RR-TB patients exhibited higher rates of resistance to isoniazid and ofloxacin compared to RS-TB patients. This pattern may reflect the longer treatment histories of RR-TB patients, increasing their exposure to various drugs and the likelihood of developing resistance (18). The isoniazid resistance rate among RR-TB patients reached 71.9%, consistent with global reports indicating that 78% of new RR-TB cases are MDR-TB (19). The high isoniazid co-resistance rate in RR-TB patients likely reflects acquired resistance due to prior inadequate treatment. Since isoniazid and rifampicin are core first-line anti-TB drugs frequently administered in combination, their concurrent use exerts substantial selective pressure for the emergence of dual resistance. This risk is particularly heightened in cases of irregular or incomplete treatment, often resulting in treatment failure and the development of multidrug-resistant tuberculosis (MDR-TB) (20, 21). Supporting this, in high-risk groups showed higher odds of co-resistance than new cases, underscoring the role of treatment failures in driving MDR development. As isoniazid and rifampicin are core anti-TB drugs often used together throughout treatment, there is significant selective pressure for dual resistance, particularly in cases of irregular treatment (22). Notably, ofloxacin resistance was also prevalent among RR-TB patients. As a key fluoroquinolone, ofloxacin exhibits incomplete cross-resistance with other fluoroquinolones in RR-TB treatment (23). Without fluoroquinolone susceptibility testing, the use of fluoroquinolone-containing regimens may compromise treatment success rates and potentially lead to additional drug resistance. Therefore, in light of the high isoniazid and ofloxacin resistance rates in Fujian, it is essential to modify existing drug resistance screening protocols to include systematic testing for both agents in RR-TB cases. Moreover, individualized RR-TB treatment regimens should be optimized based on detailed susceptibility profiles for fluoroquinolones and isoniazid to ensure therapeutic efficacy.

The treatment rate for RR-TB patients in Fujian Province was only 77%, below the national average of 79.38% in 2021 (24), and the treatment success rate was similarly low at 58.6%. Compared to several eastern provinces in China, Fujian Province demonstrates a relatively lower success rate in the treatment of rifampicin-resistant tuberculosis (RR-TB). This disparity may be attributed to differences in healthcare infrastructure, diagnostic capacity, or treatment adherence protocols (15, 25, 26). Loss to follow-up was the primary reason for unsuccessful treatment in Fujian Province. Previous researches have demonstrated that loss to follow-up among RR-TB patients is influenced by a range of independent risk factors. These include structural barriers (e.g., distance from treatment centers, rural residence), patient demographics (older age, male sex), and clinical factors (extrapulmonary TB, HIV coinfection, multidrug resistance, and delayed sputum culture conversion). Additionally, psychosocial challenges (negative treatment attitudes, limited social support), health system-related issues (dissatisfaction with care), socioeconomic disadvantage, and treatment-related adverse events further contribute to loss to follow-up (27, 28). These individuals represent significant sources of RR-TB transmission, necessitating further research and Addressing these multifaceted determinants is critical to improving RR-TB treatment adherence and outcomes.

Univariate and multivariate logistic regression analyses identified gender, age, registration category, and occupation as independent factors influencing treatment outcomes in rifampicin-resistant patients. Male, age ≥45 years, high-risk group status, and migrant worker occupation were identified as risk factors for unsuccessful treatment. Previous studies suggest that declining immunity and comorbidities in older adults complicate the clinical presentation and management of RR-TB. Gender significantly influences treatment outcomes, with male patients more likely to have unhealthy habits (e.g., smoking, alcohol use) and delayed healthcare-seeking behavior. Farmers and workers face greater economic pressures and mobility, increasing the risk of treatment interruption and loss to follow-up. High-risk groups, particularly those with multiple previous TB treatments, often harbor more complex drug resistance patterns, all of which contribute to poor treatment outcomes (29–35). Targeted interventions for these populations should be implemented within existing TB control programs to improve treatment adherence and reduce the risk of unfavorable outcomes. The recommended interventions include implement comprehensive geriatric assessments with integrated comorbidity management and nutritional supplementation programs for older adult patients, develop gender-specific behavioral interventions including smoking cessation programs and male-focused health education initiatives to improve healthcare utilization, provide economic subsidies and optimize trans-regional treatment management for Farmers and workers, introduce enhanced treatment monitoring protocols with more frequent follow-ups and expanded drug susceptibility testing for high-risk groups.

Several limitations should be considered when interpreting our findings. First, potential selection bias may have been introduced through loss to follow-up, which could impact the generalizability of our results. Notably, if patients who were lost to follow-up sought treatment elsewhere and achieved favorable outcomes, our estimates of treatment success rates may be conservative. Second, constrained by the nature of our data sources, this study had limited capacity to examine potentially important confounding variables, particularly regarding comorbidities such as diabetes and HIV status. Future studies would benefit from prospective designs that incorporate more comprehensive clinical data collection, including detailed comorbidity profiles, to facilitate more robust analyses of these potential confounders.

The rifampicin resistance (RR) rate demonstrated a consistent year-on-year decline, falling from 6.3% in 2019 to 3.1% in 2024 in Fujian Province—a trend driven largely by a 53.7% reduction in RR among new TB cases (4.1 to 1.9%). The high prevalence of isoniazid and ofloxacin resistance among RR-TB cases necessitates revising current drug resistance screening to include systematic testing for both agents in RR-TB cases. The low treatment and success rates for RR-TB patients highlight the need for improved strategies to ensure comprehensive treatment coverage and enhance treatment outcomes. Special attention should be given to male patients, those aged ≥45 years, high-risk groups and farmers or workers, who face higher risks of poor treatment outcomes. Targeted interventions such as comorbidity management, nutritional support and economic subsidies should be implemented for these patient populations to improve treatment adherence and reduce unfavorable treatment outcomes.