Discrepancies between the genotypes and phenotypes of clarithromycin-resistant Mycobacterium abscessus complex

SETTING: Macrolides are a key drug class used for the treatment of Mycobacterium abscessus complex disease.

OBJECTIVE: To verify the relationship between phenotypic susceptibility and genotypic resistance to clarithromycin (CLM).

DESIGN: Subspecies of M. abscessus complex from 145 consecutive patients were identified using hsp65 and rpoB gene sequencing, and tested for CLM susceptibility, classification into the erm(41) sequevars responsible for inducible resistance and the presence of rrl mutations associated with acquired resistance.

RESULTS: The isolates comprised 74 M. abscessus subsp. abscessus, 69 M. abscessus subsp. massiliense and two M. abscessus subsp. bolletii. M. abscessus subsp. abscessus isolates comprised 15 sequevars, with the majority corresponding to sequevar 1 (n = 24), sequevar 6 (n = 13) and sequevar 2 (n = 8). Interestingly, seven M. abscessus subsp. abscessus isolates (9.5%) presented genetically functional, but not phenotypic, inducible resistance. Moreover, rrl was mutated in only 14.3% (1/7) of acquired resistance isolates. However, M. abscessus subsp. massiliense and M. abscessus subsp. bolletii isolates with acquired resistance at day 3 showed mutations at positions 2057–2059 (P < 0.05).

CONCLUSIONS: Our study indicates that genotypic inducible and acquired resistance in M. abscessus subsp. abscessus does not always coincide with phenotypic susceptibility. Rigorous phenotypic evaluation is thus important because of the considerable impact on patients.