Inducible and Acquired Clarithromycin Resistance in the Mycobacterium abscessus Complex
Por:
Rubio, M, March, F, Garrigo, M, Moreno, C, Espanol, M, Coll, P
Publicada:
8 oct 2015
Resumen:
Purpose
Clarithromycin was considered the cornerstone for the treatment of Mycobacterium abscessus complex infections. Genetic resistance mechanisms have been described and many experts propose amikacin as an alternative. Nevertheless, clarithromycin has several advantages; therefore, it is necessary to identify the non-functional erm(41) allele to determine the most suitable treatment. The aims of this study were to characterize the molecular mechanisms of clarithromycin resistance in a collection of Mycobacterium abscessus complex isolates and to verify the relationship between these mechanisms and the antibiogram.
Materials and Methods
Clinical isolates of M. abscessus complex (n = 22) from 16 patients were identified using four housekeeping genes (rpoB, secA1, sodA and hsp65), and their genetic resistance was characterized by studying erm(41) and rrl genes. Nine strains were recovered from the clinical isolates and subjected to E-test and microdilution clarithromycin susceptibility tests, with readings at 3, 7 and 14 days.
Results
We classified 11/16 (68.8%) M. abscessus subsp. abscessus, 4/16 (25.0%) M. abscessus subsp. bolletii, and 1/16 (6.3%) M. abscessus subsp. massiliense. T28 erm(41) allele was observed in 8 Mycobacterium abscessus subps. abscessus and 3 Mycobacterium abscessus subsp. bolletii. One strain of M. abscessus subsp. bolletii had an erm(41) gene truncated and was susceptible to clarithromycin. No mutations were observed in rrl gene first isolates. In three patients, follow-up of initial rrl wild-type strains showed acquired resistance.
Conclusions
Most clinical isolates of M. abscessus complex had inducible resistance to clarithromycin and total absence of constitutive resistance. Our findings showed that the acquisition of resistance mutations in rrl gene was associated with functional and non-functional erm( 41) gene. Caution is needed when using erm(41) sequencing alone to identify M. abscessus subspecies. This study reports an acquired mutation at position 2057 of rrl gene, conferring medium-low clarithromycin constitutive resistance.
Filiaciones:
Rubio, M:
Univ Autonoma Barcelona, Dept Genet Microbiol, Bellaterra 08193, Cerdanyola Del, Spain
March, F:
Fundacio Gestio Hosp Santa Creu & Sant Pau, Serv Microbiol, Barcelona 08026, Spain
Garrigo, M:
Fundacio Gestio Hosp Santa Creu & Sant Pau, Serv Microbiol, Barcelona 08026, Spain
Moreno, C:
Fundacio Gestio Hosp Santa Creu & Sant Pau, Serv Microbiol, Barcelona 08026, Spain
Espanol, M:
Fundacio Gestio Hosp Santa Creu & Sant Pau, Serv Microbiol, Barcelona 08026, Spain
Coll, P:
Univ Autonoma Barcelona, Dept Genet Microbiol, Bellaterra 08193, Cerdanyola Del, Spain
Fundacio Gestio Hosp Santa Creu & Sant Pau, Serv Microbiol, Barcelona 08026, Spain
Gold, Green Published
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