Lack of association between rrl and erm(41) mutations and clarithromycin resistance in Mycobacterium abscessus complex

Abstract

BACKGROUND Mycobacterium abscessus complex (MABC) includes species with high resistance rates among mycobacterial pathogens. In fact, MABC infections may not respond to clarithromycin treatment, which has historically been very effective against MABC infection. Molecular markers have been proposed to detect both acquired (rrl polymorphisms) and inducible (erm(41) polymorphisms) clarithromycin resistance in MABC isolates. OBJECTIVES This study aimed to evaluate the susceptibility profile and molecular markers of clarithromycin resistance in MABC. METHODS The clarithromycin susceptibility profile was determined by broth microdilution with reads on days 3, 5, 7 and 14. Mutations in the rrl and erm(41) genes were evaluated by polymerase chain reaction (PCR) using specific primers, followed by sequencing. FINDINGS A total of 14 M. abscessus subsp. abscessus isolates and 28 M. abscessus subsp. massiliense isolates were evaluated, and clarithromycin resistance was observed in all isolates for up to three days of incubation. None of the 42 isolates exhibited a point mutation in the rrl gene, while all the isolates had a T28 polymorphism in the erm(41) gene. Moreover, all 28 M. abscessus subsp. massiliense isolates had a deletion in the erm(41) gene. MAIN CONCLUSIONS While all the MABC isolates exhibited acquired clarithromycin resistance, no isolates exhibited a point mutation in the rrl gene in this study. The M. abscessus subsp. massiliense isolates demonstrated clarithromycin resistance, which is an uncommon phenotype. The molecular data for the rrl and erm(41) genes were not consistent with the phenotypic test results of clarithromycin susceptibility, indicating a lack of correlation between molecular clarithromycin resistance markers for both acquired and inducible resistance.