Drug resistance profile of Mycobacterium kansasii clinical isolates before and after 2-month empirical antimycobacterial treatment

Mycobacterium kansasii (M. kansasii) pulmonary disease is frequently misdiagnosed and treated as tuberculosis, especially in countries with high tuberculosis burden. This study aimed to investigate the drug resistance profile of M. kansasii in patients with M. kansasii pulmonary disease in Shanghai, and to determine the variations in drug resistance after the 2-month antimycobacterial treatment.All patients diagnosed with M. kansasii pulmonary disease from 2017 to 2019 in Shanghai were retrospectively analyzed. Whole-genome sequencing (WGS) was performed and minimum inhibitory concentration (MIC) to antimycobacterial drugs was measured by broth microdilution method.In total, 191 patients were diagnosed with M. kansasii pulmonary disease. Of them, 24.1% (46/191) had persistent positive culture after two months antimycobacterial treatment. WGS found that the 46 paired isolates had a difference17 SNPs, thus excluding the possibility of exogenous reinfection. Over 90% of the baseline isolates were sensitive to either of rifampin, clarithromycin, moxifloxacin, and amikacin, while a high resistance to ethambutol (118/191, 61.8%) and 4 μg/ml isoniazid (32/191, 16.8%) were observed. Two isolates presented high resistance to rifamycin, i.e., rifampin MIC8 μg/mL and rifabutin MIC = 8 μg/mL, both containing the rpoB mutation (S454L). The increase of MIC to rifampin, ethambutol, and/or isoniazid was identified in 56.5% (26/46) of patients.A high prevalence of innate resistance to ethambutol and isoniazid was observed among circulating M. kansasii clinical strains in Shanghai. The increase of drug resistance under empirical antimycobacterial treatment highlighted the urgency of definitive species identification before initiating treatment.