Clinical and laboratory determinants of treatment response and rifampicin resistance among Xpert MTB/RIF-confirmed extrapulmonary tuberculosis patients: A prospective study from Central India

Extrapulmonary tuberculosis (EPTB) contributes significantly to the global tuberculosis burden, yet treatment response and drug resistance remain poorly characterized. India, a high- tuberculosis burden country, faces growing challenges of delayed diagnosis, treatment and drug-resistant tuberculosis, particularly in extrapulmonary forms. This study evaluated early clinical response to therapy and identified factors associated with rifampicin resistance among patients with EPTB. A prospective observational study was conducted at a tertiary care centre in central India between 2018 and 2024. A total of 532 patients with microbiologically confirmed EPTB, based on the Xpert MTB/RIF assay, were included. The study collected baseline demographic, clinical, and laboratory data. Clinical response at 8 weeks was assessed using standardized criteria. Multivariable logistic regression analysis identified factors associated with slow clinical response and rifampicin resistance. A total of 5,764 presumptive EPTB samples were tested using the Xpert MTB/RIF assay. Among these, 532 patients had confirmed EPTB. Rifampicin resistance was detected in 36 patients (6.7%), while 496 patients had rifampicin-sensitive disease and were included in the response analysis. Among these patients, 113 (22.8%) demonstrated slow clinical response. Slow response showed independent association with HIV co-infection, diabetes mellitus, malnutrition, chronic obstructive pulmonary disease, prolonged symptom duration, and non-lymph node disease, particularly abdominal and genitourinary tuberculosis. Socioeconomic factors, such as rural residence and lower educational status, also showed independent association. Elevated inflammatory markers, including erythrocyte sedimentation rate and C-reactive protein, showed independent association with slow clinical response. Rifampicin resistance showed independent association with previous tuberculosis, HIV infection, male sex, and disseminated disease. A significant overlap existed between delayed clinical response and drug resistance, as rifampicin resistance occurred more frequently among slow responders than among responders (12.3% vs. 4.1%, p = 0.002). Nearly one-quarter of patients with EPTB demonstrated delayed clinical response at 8 weeks. Both host-related and disease-related factors showed association with treatment response, while rifampicin resistance showed strong association with prior tuberculosis and immunosuppression. The overlap between slow clinical response and drug resistance highlighted the importance of early molecular diagnostics and targeted clinical monitoring in high-risk patients.