Erm(41)-dependent inducible resistance to azithromycin and clarithromycin in clinical isolates of Mycobacterium abscessus.
OBJECTIVE
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.
Institut für Medizinische Mikrobiologie, Universität Zürich, Gloriastrasse 30/32, 8006 Zürich, Switzerland Nationales Zentrum für Mykobakterien, Universität Zürich, Gloriastrasse 30/32, 8006 Zürich, Switzerland.
Florian P
FP
Maurer
Institut für Medizinische Mikrobiologie, Universität Zürich, Gloriastrasse 30/32, 8006 Zürich, Switzerland.
Claudio
C
Castelberg
Institut für Medizinische Mikrobiologie, Universität Zürich, Gloriastrasse 30/32, 8006 Zürich, Switzerland.
Chantal
C
Quiblier
Institut für Medizinische Mikrobiologie, Universität Zürich, Gloriastrasse 30/32, 8006 Zürich, Switzerland Nationales Zentrum für Mykobakterien, Universität Zürich, Gloriastrasse 30/32, 8006 Zürich, Switzerland.
Erik C
EC
Böttger
Institut für Medizinische Mikrobiologie, Universität Zürich, Gloriastrasse 30/32, 8006 Zürich, Switzerland Nationales Zentrum für Mykobakterien, Universität Zürich, Gloriastrasse 30/32, 8006 Zürich, Switzerland asomoskoevi@imm.uzh.ch.
Akos
A
Somoskövi
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017963:Azithromycin / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D017291:Clarithromycin / Q000494:pharmacology*; D003470:Culture Media / Q000737:chemistry; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005798:Genes, Bacterial; D006801:Humans; D018942:Macrolides / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects* / Q000235:genetics*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003470:Culture Media; D018942:Macrolides; D017963:Azithromycin; D017291:Clarithromycin
drug susceptibility testing; inducible resistance; macrolides; rapidly growing mycobacteria