Clinical characteristics, drug resistance profiles, and inflammatory cytokine signatures in newly treated versus retreated MDR/RR-TB patients: associations with treatment outcomes.

BACKGROUND

Multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) poses a significant threat to global tuberculosis control. Understanding drug resistance profiles, immune signatures, and their associations with treatment outcomes is critical.

METHODS

A total of 395 MDR/RR-TB patients were enrolled. Baseline characteristics, minimum inhibitory concentrations (MICs) for multiple anti-TB drugs, plasma inflammatory cytokine levels, and treatment outcomes were analyzed.

RESULTS

The cohort was predominantly male (69.6%), with a median age of 40 years. Pre-extensively drug-resistant (Pre-XDR-TB) accounted for 48.4%, and treatment success rate was 66.8%. Retreated patients showed significantly higher MICs for ethambutol, isoniazid, rifampicin, moxifloxacin, ofloxacin, and streptomycin (all p < 0.05). Strong cross-resistance was observed between moxifloxacin and ofloxacin (ρ = 0.93, p < 0.0001). Retreated patients had lower IL-2 (p = 0.035) and higher IL-12 levels (p = 0.002). Unadjusted analyses identified significant associations between elevated MICs of isoniazid, moxifloxacin, ofloxacin, and streptomycin and treatment failure. After multivariable adjustment for age, sex, treatment history, and diabetes, ethambutol (aOR = 1.620, p = 0.007) and isoniazid (aOR = 1.315, p = 0.018) showed positive associations with treatment failure, though these did not remain significant after false discovery rate correction for multiple comparisons.

CONCLUSION

In MDR/RR-TB patients, elevated ethambutol and isoniazid MICs were associated with treatment failure after multivariable adjustment; however, these associations were not significant after multiple comparisons correction. The potential prognostic value of quantitative MIC testing for these drugs remains to be established in future adequately powered studies.