Erm(41)-dependent inducible resistance to azithromycin and clarithromycin in clinical isolates of Mycobacterium abscessus

• Published in: Journal of antimicrobial chemotherapy 2014-06, Vol.69 (6), p.1559-1563
• Main Authors: Maurer, Florian P., Castelberg, Claudio, Quiblier, Chantal, Böttger, Erik C., Somoskövi, Akos
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Azithromycin - pharmacology; Bacteria; Bacterial Proteins - genetics; Clarithromycin - pharmacology; Comparative analysis; Culture Media - chemistry; Drug resistance; Drug Resistance, Bacterial - genetics; Genes, Bacterial; Genotype & phenotype; Humans; Macrolides - pharmacology; Medical treatment; Microbial Sensitivity Tests; Mycobacterium - drug effects; Mycobacterium - genetics; Mycobacterium abscessus; Mycobacterium chelonae
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dku007

Objectives The ribosomal methylase Erm(41) confers inducible resistance to macrolides in Mycobacterium abscessus. The aim of this work was to systematically study and compare drug susceptibility to clarithromycin and azithromycin in M. abscessus and Mycobacterium chelonae clinical isolates with a particular focus on inducible drug resistance. Methods Clinical isolates of M. abscessus subsp. abscessus (n = 21), M. abscessus subsp. bolletii (n = 16), M. abscessus subsp. massiliense (n = 10) and M. chelonae (n = 22) were characterized regarding their erm(41) and rrl genotypes and subjected to drug susceptibility testing (DST) for clarithromycin and azithromycin. Microdilution DST was performed in cation-adjusted Mueller–Hinton broth (pH 7.4) with readings at days 3, 7 and 12 and with pre-incubation at subinhibitory macrolide concentrations for erm(41) induction. In addition, the influence of variations in pH and growth medium on DST results was examined. Results MICs of azithromycin were consistently higher than those of clarithromycin. In strains with an inducible erm(41) gene, high median MICs of ≥256 mg/L on day 12 were observed for both clarithromycin and azithromycin. Inducible resistance was at least as pronounced for azithromycin as for clarithromycin. Conclusions Our findings do not support the suggestion of a preferential use of azithromycin over clarithromycin in order to limit inducible macrolide resistance. Both compounds provoked a comparable resistance phenotype in M. abscessus. Caution is needed when using either azithromycin or clarithromycin for treatment of M. abscessus infections.