Direct observation therapy with appropriate treatment regimens was associated with a decline in second-line drug-resistant tuberculosis in Taiwan.

The resistance of Mycobacterium tuberculosis (MTB) to second-line drugs (SLDs) is growing worldwide; however, associations between the appropriateness of treatment for tuberculosis (TB) and whether the directly observed treatment, short course (DOTS)/DOTS-plus programs had an impact on the prevalence of SLD-resistant MTB are still uncertain. We performed a retrospective analysis of resistance profiles among MTB isolates obtained from 6,035 consecutive patients from 2004 to 2011 at two TB referral hospitals in Taiwan. There was a significant decrease (all p-values <0.01) in the prevalence of MTB isolates that were resistant to fluoroquinolones, injectable SLDs, and orally administered SLDs, and multidrug-resistant (MDR) and extensively drug-resistant (XDR) MTB isolates over time. There was a significant increase in the coverage rate of DOTS/DOTS-plus programs and that of administering appropriate first-line and second-line regimens (all p < 0.01). Compared with isoniazid-susceptible isolates, high-level (1.0 mg/L) isoniazid-resistant and MDR isolates showed extensive cross resistance to ofloxacin (5.9%, p < 0.01 and 33.6%, p < 0.01), levofloxacin (9.6%, p < 0.01 and 38.1%, p < 0.01), moxifloxacin (11.1%, p < 0.01 and 26.5%, p < 0.01), kanamycin (6.8 %, p < 0.01 and 16.7 %, p < 0.01), ethionamide (6.4%, p < 0.01 and 16.2%, p < 0.01), and para-aminosalicylic acid (13.1%, p < 0.01 and 20.4%, p < 0.01), but not to capreomycin (2.0%, p = 0.06 and 1.6%, p = 0.08). The decline in prevalence of resistance to SLDs was negatively correlated with the rise in rates of administering appropriate regimens as well as the DOTS/DOTS-plus programs, but not with the increase in usage of second-line regimens. The implementation of DOTS/DOTS-plus programs with appropriate regimens was associated with a decrease in the prevalence of SLD-resistant and XDR TB.