Zofia Bakuła, Jacek Bielecki, Aleksandra Safianowska, Lian Pennings, Tomasz Jagielski, Małgorzata Proboszcz, Magdalena Modrzejewska, Jakko van Ingen
Studies on drug susceptibility of Mycobacterium kansasii are very few and involve limited number of strains. The purpose of this study was to determine drug susceptibility profiles of M. kansasii isolates representing a spectrum of species genotypes (subtypes) with two different methodologies, i.e. broth microdilution and E-test assays. To confirm drug resistance, drug target genes were sequenced.A collection of 85 M. kansasii isolates, including representatives of eight different subtypes (I-VI, I/II, IIB) from eight countries was used. Drug susceptibility against 13 and 8 anti-mycobacterial agents was tested by using broth microdilution and E-test method, respectively. For drug-resistant or high-MIC isolates, eight structural genes (rrl, katG, inhA, embB, rrs, rpsL, gyrA, and gyrB) and one regulatory region (embCA) were PCR-amplified and sequenced in the search for resistance-associated mutations.All isolates tested were susceptible to rifampicin (RIF), amikacin (AMK), co-trimoxazole (SXT), rifabutin (RFB), moxifloxacin (MXF), and linezolid (LZD), when using 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 E-test 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 rrl gene (CLR-resistant strain) and A128G transition at rpsL gene (strain with STR MIC >64 mg/L).In conclusion, eight drugs, including RIF, CLR, AMK, SXT, RFB, MXF, LZD, and ethionamide (ETO) showed high in vitro activity against M. kansasii isolates. Discrepancies of the results between the reference microdilution method and E-test precludes the use of the latter for drug susceptibility determination in M. kansasii Drug resistance in M. kansasii may have different genetic determinants than resistance to the same drugs in M. tuberculosis.
