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


Maurer, Florian P; Castelberg, Claudio; Quiblier, Chantal; Böttger, Erik C; Somoskövi, Akos (2014). Erm(41)-dependent inducible resistance to azithromycin and clarithromycin in clinical isolates of Mycobacterium abscessus. Journal of Antimicrobial Chemotherapy, 69(6):1559-1563.

Abstract

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.

Abstract

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Microbiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Date:2014
Deposited On:19 Mar 2014 13:37
Last Modified:05 Apr 2016 17:41
Publisher:Oxford University Press
ISSN:0305-7453
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/jac/dku007
PubMed ID:24500188

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