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.OBJECTIVESThis study aimed to evaluate the susceptibility profile and molecular markers of clarithromycin resistance in MABC.METHODSThe 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.FINDINGSA 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 CONCLUSIONSWhile 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.

Analysis of drug-susceptibility patterns and gene sequences associated with clarithromycin and amikacin resistance in serial Mycobacterium abscessus isolates from clinical specimens from Northeast Thailand

“…Several studies have investigated the roles of erm(41) and rrl of M . abscessus in conferring resistance to clarithromycin [9–12], but with inconsistent results [13]. These mutations did not explain all clarithromycin-resistant M .…”

“…These mutations did not explain all clarithromycin-resistant M . abscessus strains [13] and other mechanisms might exist. Amikacin resistance is also partially explained by point mutations at positions 1,406 to 1,409 in the rrs gene encoding 16S rRNA [8, 14, 15].…”

Whole-Genome Sequences of Mycobacterium abscessus subsp. massiliense Isolates from Brazil

“…Infections caused by the MABSC are becoming more prevalent worldwide ( 5 ), including in Brazil, which has reported 2,128 skin and soft tissue infections since 2004, with significant outbreaks ( 6 ). The effective treatment of infections caused by the MABSC is challenged by the high resistance to antibiotics displayed by these organisms ( 5 , 7 ).…”

An Update in Antimicrobial Therapies and Infection Prevention in Pediatric Lung Transplant Recipients

“…Because there is poor correlation between in vitro antibiotic susceptibility testing and in vivo efficacy, increasing hope had been placed on the development of commercial molecular assays to identify these molecular markers of resistance [56]. Unfortunately, however, reports of the positive correlation between genotypic and phenotypic testing for resistance have been conflicting [55,58,59]. Furthermore, significant variations in genotypic and phenotypic resistance patterns have been observed based on geography [55].…”