Melting the eis : Nondetection of Kanamycin Resistance Markers by Routine Diagnostic Tests and Identification of New eis Promoter Variants

• Published in: Antimicrobial agents and chemotherapy 2021-06, Vol.65 (7), p.e0250220-e0250220
• Main Authors: Ley, Serej D, Pillay, Samantha, Streicher, Elizabeth M, van der Heijden, Yuri F, Sirgel, Frederik, Derendinger, Brigitta, de Kock, Marianna, Gagneux, Sébastien, Warren, Robin M, Theron, Grant, de Vos, Margaretha
• Format: Article
• Language: English
• Subjects: Antitubercular Agents - pharmacology; Antitubercular Agents - therapeutic use; Diagnostic Tests, Routine; Drug Resistance, Multiple, Bacterial; Genotype; Humans; Kanamycin - pharmacology; Kanamycin Resistance - genetics; Mechanisms of Resistance; Microbial Sensitivity Tests; Mutation - genetics; Mycobacterium tuberculosis - genetics; Tuberculosis, Multidrug-Resistant - diagnosis; Tuberculosis, Multidrug-Resistant - drug therapy; Tuberculosis, Multidrug-Resistant - genetics
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.02502-20

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