Factors Affecting Treatment Outcomes in Second-Line Drug-Resistant Tuberculosis

The emergence of drug-resistant tuberculosis jeopardizes the TB control programme activities globally. Multidrug-resistant TB is defined as tuberculosis strains resistant to at least two first-line drugs, rifampicin (RIF) and isoniazid (INH). Extensively drug-resistant TB refers to the resistance against any fluoroquinolone drug and one of the second-line injectable drugs (i.e., amikacin, kanamycin, or capreomycin). Mutations in gyrA and gyrB lead to acquired resistance to fluoroquinolones and these have been widely used as predictive markers for fluoroquinolones resistance in molecular diagnostics. The present study aimed to analyze the treatment outcomes and risk factors associated with fluoroquinolone drug resistance due to mutations in the gyrA and gyrB genes. A total of 258 pulmonary tuberculosis (TB) samples resistant to first-line drugs (H, R, or HR) were tested using the GenoType MTBDRsl assay for the molecular detection of mutations. Among these samples, 251 were identified as drug-resistant tuberculosis (DR-TB), while seven were sensitive to all first-line anti-TB drugs. Of the 251 DR-TB cases, 42 were classified as multidrug-resistant tuberculosis (MDR-TB), 200 as isoniazid mono-resistant, and nine as rifampicin mono-resistant. The analysis of the DR-TB cases using the MTBDRsl assay revealed that 14 cases had pre-extensively drug-resistant (pre-XDR) fluoroquinolone, one had pre-XDR with a second-line injectable, and one case was classified as extensively drug-resistant tuberculosis (XDR-TB). The remaining 235 cases were sensitive to both fluoroquinolone and second-line injectable drugs. The median age of the study group was 42.7 years (± 16.4 years). The overall successful treatment outcomes were 70.6% for MDR-TB, 82.0% for isoniazid mono-resistant cases, and 51% for pre-XDR patients. The risk of unfavorable outcomes was significantly increased for pre-XDR, isoniazid mono-resistant, and XDR cases, with a relative risk of 2.14, indicating a 113.84% increased risk (95% CI: 0.7821–5.8468). An independent risk factor associated with treatment failure showed a 77.78% increased risk, with a relative risk of 1.78 (95% CI: 0.3375–9.3655). Logistic regression analysis revealed significant relative risks among MDR-TB patients: resistance (OR: 4.00), male gender (OR: 2.02), being aged 61 years and older (OR: 2.26), and having diabetes (OR: 1.075) were associated with increased risks of 84.62%, 95.83%, and 4.76%, respectively. For isoniazid mono-resistant cases, significant independent risk factors included being aged 16-60 (OR: 1.16) and being 61 years or older (OR: 1.18). This study highlights the significant risks associated with isoniazid mono-resistance, pre-XDR, and MDR tuberculosis among males, young adults, individuals with diabetes, and patients with a history of treatment failure. The correlation of the mutation region in the target gene with the patient’s outcome might give better insight into drug-resistant tuberculosis management for controlling tuberculosis effectively. Timely identification of high-risk patients will be crucial for effectively controlling drug-resistant tuberculosis.