Assessment of Clarithromycin Susceptibility in Strains Belonging to theMycobacterium abscessusGroup byerm(41) andrrlSequencing

Abstract

ABSTRACTClarithromycin was the drug of choice forMycobacterium abscessusinfections until inducible resistance due toerm(41) was described. BecauseM. abscessuswas split intoM. abscessussensu stricto,Mycobacterium massiliense, andMycobacterium bolletii, we looked forerm(41) in the three species and determined their clarithromycin susceptibility levels. Ninety strains were included: 87 clinical strains from cystic fibrosis patients (61%) and others (39%), representing 43M. abscessus, 30M. massiliense, and 14M. bolletiistrains identified on a molecular basis, and 3 reference strains. Clarithromycin and azithromycin MICs were determined by broth microdilution and Etest with a 14-day incubation period. Mutations inrrl(23S rRNA gene) known to confer acquired clarithromycin resistance were also sought.erm(41) was detected in all strains but with two deletions in allM. massiliensestrains. These strains were indeed susceptible to clarithromycin (MIC90of 1 μg/ml) except for four strains withrrlmutations.M. abscessusstrains harbored an intacterm(41) but had a T/C polymorphism at the 28th nucleotide: T28 strains (Trp10 codon) demonstrated inducible clarithromycin resistance (MIC90of >16 μg/ml), while C28 strains (Arg10) were susceptible (MIC90of 2 μg/ml) except for two strains withrrlmutations.M. bolletiistrains haderm(41) sequences similar to the sequence of the T28M. abscessusgroup, associated with inducible clarithromycin resistance (MIC90of >16 μg/ml).erm(41) sequences appeared species specific within theM. abscessusgroup and were fully concordant with clarithromycin susceptibility whenerm(41) sequencing was associated with detection ofrrlmutations. Clarithromycin-resistant strains, including the sixrrlmutants, were more often isolated in cystic fibrosis patients, but this was not significantly associated with a previous treatment.