Relationship between the isoniazid-resistant mutation katGS315T and the prevalence of MDR-/XDR-TB in Osaka, Japan

To determine the prevalence of katGS315T mutations in isoniazid (INH) resistant Mycobacterium tuberculosis and to elucidate the association of katGS315T mutations with the prevalence of multidrug-resistant tuberculosis (MDR-TB).

From 2001 to 2004, 1655 isolates from all newly registered patients who visited the Osaka Prefectural Medical Centre for Respiratory and Allergic Diseases were tested for drug susceptibility. Genotyping was performed using insertion sequence (IS) 6110-restriction fragment length polymorphism (RFLP) in 1629 of 1655 (98.4%) cases. All 145 isolates of INH-resistant M. tuberculosis, including MDR strains, were tested to detect the katGS315T mutation.

Five hundred and sixty isolates (34.4%) shared an RFLP pattern. Of the 145 INH-resistant isolates, 18/48 (37.5%) isolates belonging to the RFLP cluster had katGS315T and 23/97 (23.7%) did not have the mutation. Of the 66 MDR-TB cases, 18/29 (62.1%) isolates belonging to the RFLP cluster had katGS315T and 11/37 (29.7%) did not have the mutation. Of the 29 extensively drug-resistant (XDR) TB cases, 17/21 (80.9%) isolates belonging to the RFLP cluster had katGS315T and 3/8 (37.5%) did not have the mutation.

The clustering rate by IS6110-RFLP was very high among MDR-/XDR-TB isolates with katGS315T. Our study indicates a strong correlation between the katGS315T mutation and the transmission dynamics of MDR-TB, and especially XDR-TB.