Melting the Eis: non-detection of kanamycin resistance markers by routine diagnostic tests and identification of new eis-promoter variants.

Eis-promoter mutations can confer reduced Mycobacterium tuberculosis kanamycin susceptibility. GenoType MTBDRsl, a widely used assay evaluating this region, wrongly classified 17/410 isolates as eis-promoter wildtype. 6/17 isolates harbored mutations known to confer kanamycin resistance, and the remainder harbored either novel eis-promoter mutations (7/11) or disputed mutations (4/11). GenoType MTBDRsl can miss established and new variants that cause reduced susceptibility. These data highlight the importance of reflex phenotypic kanamycin testing.