Genotypic and phenotypic drug-resistance detection and prevalence of heteroresistance in patients with isoniazid- and multidrug-resistant tuberculosis in Ethiopia

Objective: To assess the agreement between genotypic and phenotypic methods for detecting drug resistance, and examine the prevalence of heteroresistance among isoniazid (INH)- and multidrug/rifampicin-resistant (MDR/RR) TB. Method: In total, 127 Mycobacterium tuberculosis (Mtb) isolates, including 65 MDR/RR and 62 INH resistant, were used. First-line drug susceptibility testing (DST) was performed using the LJ method to determine the percentage of resistant bacteria. All drug-resistant isolates underwent testing with LPA. Heteroresistance was defined as simultaneous detection of wild-type and resistance-conferring mutations using LPA. Result: The sensitivity of LPA (compared with LJ DST) was 96% for any INH-resistant TB and 94% for any RR TB. The prevalence of heteroresistance among the 123. Mtb isolates was 9.8%. The percentage of resistant bacteria ranged from 1% to 10% for heteroresistant TB. Rifampicin heteroresistance was detected in 1.6% of MDR TB patients. INH heteroresistance was detected in 1.6% and 16.7% of MDR and INH-resistant TB patients, respectively. The proportion of INH heteroresistance was significantly higher (p = 0.030) in persons living with HIV. Conclusion: Some phenotypic drug resistances were not captured by LPA. The prevalence and percentage of resistant bacteria among heteroresistant TB highlight the importance of LPA for early detection of heteroresistant TB.