Discordance in Phenotypic and Genotypic Susceptibility Testing for Streptomycin Due to Nonsynonymous/Nonsense/Deletion Frame-Shift Mutations in <i>gidB</i> among Clinical <i>Mycobacterium tuberculosis</i> Isolates in Kuwait

Abstract

<b><i>Objective:</i></b> Increasing reports of resistance to newer antituberculosis drugs have prompted the search for other alternative drugs. Streptomycin (STR) could be used for the treatment of drug-resistant tuberculosis if susceptibility of <i>Mycobacterium tuberculosis</i> isolate to STR could be accurately detected. We performed phenotypic and genotypic drug susceptibility testing (DST) of 118 <i>M. tuberculosis</i> isolates for STR. <b><i>Materials and Methods:</i></b> Fifty pansusceptible and 68 multidrug-resistant <i>M. tuberculosis</i> (MDR-TB) isolates were used. Phenotypic DST for STR, rifampicin, isoniazid, and ethambutol was performed by mycobacteria growth indicator tube 960 System. Genotypic DST was done by GenoTypeMTBDR<i>plus</i> assay for rifampicin and isoniazid and by PCR-sequencing of <i>rpsL</i>, <i>rrs</i>, and <i>gidB</i> genes for STR. MDR-TB isolates were genotyped by spoligotyping. <b><i>Results:</i></b> Phenotypic DST identified 50 isolates susceptible to all four drugs (pansusceptible). Sixty-one of 68 MDR-TB isolates were resistant to STR. Genotypic testing for rifampicin and isoniazid yielded expected results. Fifty pansusceptible and 7 STR-susceptible MDR-TB isolates contained no mutation in <i>rpsL</i> or <i>rrs</i>, while 47, 2, and 1 STR-resistant isolate contained <i>rpsL</i>, <i>rrs</i>, and <i>rpsL</i> + <i>rrs</i> mutations, respectively. Of the remaining 11 STR-resistant MDR-TB, 9 isolates contained deletion frame-shift/nonsynonymous mutations in <i>gidB</i>. Surprisingly, 13 pansusceptible isolates also contained deletion frame-shift/nonsense/nonsynonymous mutations in <i>gidB</i>. Also, 30 of 68 MDR-TB but only 2 of 50 pansusceptible isolates belonged to the Beijing genotype. <b><i>Conclusions:</i></b> Our data show that, like rifampicin, ethambutol, and pyrazinamide, STR also exhibits discordant phenotypic and genotypic DST results for some <i>M. tuberculosis</i> isolates. Hence, STR should be included in therapy regimens only if both phenotypic and genotypic resistance testing indicate susceptibility to avoid amplification of resistance and drug toxicity.