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

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Erm(41)-dependent inducible resistance to azithromycin and clarithromycin in clinical isolates of Mycobacterium abscessus. / Maurer, Florian P.

in: J ANTIMICROB CHEMOTH, Jahrgang 69, Nr. 6, 06.2014, S. 1559-63.

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@article{ecce8db18a2e4c3eacef8dc29caf89ee,
title = "Erm(41)-dependent inducible resistance to azithromycin and clarithromycin in clinical isolates of Mycobacterium abscessus",
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.",
keywords = "Anti-Bacterial Agents, Azithromycin, Bacterial Proteins, Clarithromycin, Culture Media, Drug Resistance, Bacterial, Genes, Bacterial, Humans, Macrolides, Microbial Sensitivity Tests, Mycobacterium, Journal Article, Research Support, Non-U.S. Gov't",
author = "Maurer, {Florian P}",
note = "{\textcopyright} The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.",
year = "2014",
month = jun,
doi = "10.1093/jac/dku007",
language = "English",
volume = "69",
pages = "1559--63",
journal = "J ANTIMICROB CHEMOTH",
issn = "0305-7453",
publisher = "Oxford University Press",
number = "6",

}

RIS

TY - JOUR

T1 - Erm(41)-dependent inducible resistance to azithromycin and clarithromycin in clinical isolates of Mycobacterium abscessus

AU - Maurer, Florian P

N1 - © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

PY - 2014/6

Y1 - 2014/6

N2 - 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.

AB - 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.

KW - Anti-Bacterial Agents

KW - Azithromycin

KW - Bacterial Proteins

KW - Clarithromycin

KW - Culture Media

KW - Drug Resistance, Bacterial

KW - Genes, Bacterial

KW - Humans

KW - Macrolides

KW - Microbial Sensitivity Tests

KW - Mycobacterium

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1093/jac/dku007

DO - 10.1093/jac/dku007

M3 - SCORING: Journal article

C2 - 24500188

VL - 69

SP - 1559

EP - 1563

JO - J ANTIMICROB CHEMOTH

JF - J ANTIMICROB CHEMOTH

SN - 0305-7453

IS - 6

ER -