Drug Susceptibility Profiling and Genetic Determinants of Drug Resistance in Mycobacterium kansasii

Abstract

Very few studies have examined drug susceptibility of , and they involve a limited number of strains. The purpose of this study was to determine drug susceptibility profiles of isolates representing a spectrum of species genotypes (subtypes) with two different methodologies, i.e., broth microdilution and Etest assays. To confirm drug resistance, drug target genes were sequenced. A collection of 85 isolates, including representatives of eight different subtypes (I to VI, I/II, and IIB) from eight countries, was used. Drug susceptibility against 13 and 8 antimycobacterial agents was tested by using broth microdilution and Etest, respectively. For drug-resistant or high-MIC isolates, eight structural genes (, ,, ,, ,, and ) and one regulatory region () were PCR amplified and sequenced in the search for resistance-associated mutations. All isolates tested were susceptible to rifampin (RIF), amikacin (AMK), co-trimoxazole (SXT), rifabutin (RFB), moxifloxacin (MXF), and linezolid (LZD) according to the microdilution method. Resistance to ethambutol (EMB), ciprofloxacin (CIP), and clarithromycin (CLR) was found in 83 (97.7%), 17 (20%), and 1 (1.2%) isolate, respectively. The calculated concordance between the Etest and dilution method was 22.6% for AMK, 4.8% for streptomycin (STR), 3.2% for CLR, and 1.6% for RIF. For EMB, INH, and SXT, not even a single MIC value determined by one method equaled that by the second method. The only mutations disclosed were A2266C transversion at the gene (CLR-resistant strain) and A128G transition at the gene (strain with STR MIC of >64 mg/liter). In conclusion, eight drugs, including RIF, CLR, AMK, SXT, RFB, MXF, LZD, and ethionamide (ETO), showed high activity against isolates. Discrepancies of the results between the reference microdilution method and Etest preclude the use of the latter for drug susceptibility determination in Drug resistance in may have different genetic determinants than resistance to the same drugs in .

Genomic Insights Into the Mycobacterium kansasii Complex: An Update

“…The INH and ETO MICs were low, and within relatively narrow ranges (<0.25-2 mg/L vs. <0.3-0.6 mg/L). These findings confirm the key observations from previous studies, on the susceptibility of M. kansasii strains to RIF and their high resistance to EMB (da Silva Telles et al, 2005;Wu et al, 2009;Shahraki et al, 2017;Bakuła et al, 2018c). This, confronted with the ATS recommendation of a three-drug (INH-RIF-EMB) regimen for the treatment of M. kansasii disease, speaks for exclusion of EMB and its replacement with other potent drug, such as moxifloxacin.…”

“…**Results according to Shahraki et al (2017). ***Results according to Tagini et al (2019 Please note, that for some isolates those data were reported elsewhere (Bakuła et al, 2018c). a According to the WGS-based (MiSI method) grouping.…”

Non-Tuberculous Mycobacterial Pulmonary Disease Prevalence Status in China

“…Except ethambutol (83.87% vs 20.5%), the resistant rate in our study is lower than previous study, clarithromycin (0 vs 20.5%), amikacin (0 vs 5.1%), rifampicin (6.45% vs 56.4%), rifabutin (3.23%% vs 34.6%), moxi oxacin (0 vs 16.7%) and linezolid (3.23%% vs 32.1%). Our result is similar with a report which used 85 M. kansassi obtained from 8 countries in Europe and Asia [37]. All isolates tested in that study were susceptible to rifampicin, amikacin, rifabutin, moxi oxacin, and linezolid.…”

Mutations in gyrA and gyrB in Moxifloxacin-Resistant Mycobacterium avium Complex and Mycobacterium abscessus Complex Clinical Isolates

“…In another report on ciprofloxacin-resistant isolates from South Korea, 12 M. abscessus isolates and 17 M. massiliense isolates had no DNA gyrase gene mutations (24). In addition, a recent study from Poland reported that 17 ciprofloxacinresistant M. kansasii isolates did not harbor any changes in gyrA or gyrB (31).…”