Predicting isoniazid resistance in Mycobacterium tuberculosis complex in New York State using whole-genome sequencing

Isoniazid (INH) is one of the two most critical antibiotics used as part of standard treatment of tuberculosis and is also used as preventative therapy for contacts of tuberculosis patients, despite having a higher rate of drug resistance than all other antibiotics used in standard therapy. Furthermore, isoniazid resistance typically precedes rifampin resistance in the development of multidrug-resistant TB. As such, the reliable detection of INH resistance is crucial for case management and to limit the acquisition of additional drug resistance. The present study describes a whole-genome sequencing approach to predicting INH resistance from clinical isolates and models how this technology can be used within a reduced phenotypic drug susceptibility testing algorithm to limit duplicate testing, saving resources and time while maintaining the sensitivity of resistance detection.