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

Objectives Mycobacterium 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 2 months of antimycobacterial treatment. Methods All patients with a diagnosis of M. kansasii pulmonary disease from 2017 to 2019 in Shanghai were retrospectively analysed. Whole-genome sequencing was performed, and the minimum inhibitory concentration (MIC) to antimycobacterial drugs was measured using the broth microdilution method. Results In total, 191 patients had a diagnosis of M. kansasii pulmonary disease. Of them, 24.1% (46/191) had persistent positive culture after 2 months of antimycobacterial treatment. Whole-genome sequencing revealed that the 46 paired isolates had a difference of <17 single nucleotide polymorphisms, thus excluding the possibility of exogenous reinfection. More than 90% of the baseline isolates were sensitive to rifampin, clarithromycin, moxifloxacin, or amikacin, whereas a high resistance to ethambutol (118/191, 61.8%) and 4 μg/mL of isoniazid (32/191, 16.8%) were observed. Two isolates presented high resistance to rifamycin (i.e. a rifampin MIC of >8 μg/mL and a rifabutin MIC of 8 μg/mL) both containing the rpoB mutation (S454L). The increase of MIC to rifampin, ethambutol, and/or isoniazid was identified in 50.0% (23/46) of the patients. Discussion A high prevalence of innate resistance to ethambutol and isoniazid was observed among circulating M. kansasii clinical strains in Shanghai. The increase in drug resistance under empirical antimycobacterial treatment highlighted the urgency of definitive species identification before initiating treatment.