Molecular mechanisms of clarithromycin resistance in Mycobacterium abscessus complex clinical isolates from Venezuela

• Based on the sequence of the erm(41) gene, 20 strains were identified as Mycobacterium abscessus, 2 as M. bolletii and 4 as M. massiliense.
• 35% of the M. abscessus complex strains were resistant to clarithromycin (CLR), none of which contained a mutation in the rrl gene.
• 7 M. abscessus strains and 2 clinical isolates of M. bolletii were T28 sequevars.
• In these strains, the resistant phenotype to CLR is due only to an inducible resistance mechanism conferred by the erm(41) gene.

In this study, 26 clinical isolates of Mycobacterium abscessus complex strains were characterised using available identification algorithms for the three species (M. abscessus, M. massiliense and M. bolletii) and the genotypic characteristics of clarithromycin (CLR) resistance were determined. Strains were identified by PCR restriction fragment length polymorphism analysis of the hsp65 and erm(41) gene sequences. Susceptibility to CLR was determined by the broth microdilution method. The mechanism of resistance to this macrolide was evaluated by sequencing the erm(41) and rrl genes. Mutations and/or deletions associated with resistance to CLR as determined in this study were those that have been previously described. No constitutive resistance to CLR was found, however 35% (9/26) of the M. abscessus complex strains tested had a functional inducible erm(41) gene. Based on sequencing of this gene, the strains of M. abscessus were separated into six sequevars, of which only two are consistent with those previously reported. In conclusion, we demonstrated that the low percentage of strains with a resistant phenotype to CLR was due only to an inducible resistance mechanism conferred by the erm(41) gene and not to mutations in the rrl gene. CLR can still be useful for treatment in some Venezuelan patients infected with a member of the M. abscessus group, but drug resistance testing and/or molecular analysis must precede the prescription of this antibiotic.