Molecular epidemiology of Mycobacterium abscessus complex in cystic fibrosis and non cystic fibrosis patients in New South Wales.

Abstract

To improve management of infectious caused by Mycobacterium abscessus and to translate genomic analysis of M. abscessus into practice of the New South Wales Mycobacterium Reference Laboratory. Members of the Mycobacterium abscessus complex are emerging pathogens of increasing importance, causing both respiratory and soft tissue infections. It includes three clinically relevant subspecies, M. abscessus subsp. abscessus, M. abscessus subsp. bolletti, and M. abscessus subsp. massiliense, with their own drug susceptibility profiles. The aim of this study was to examine the subspecies and antibiotic susceptibilities combining phenotypic and genotypic information. Clinical isolates were collected between 2015 to 2017 at the statewide New South Wales Mycobacterium Reference Laboratory, Australia. Drug susceptibility testing was performed for four main drugs (clarithromycin, amikacin, ciprofloxacin, linezolid) by broth micro dilution. Analysis of mutations associated with drug resistance was done by analyzing whole genome sequencing data. Furthermore, the analysis was extended to determine genetic diversity between subspecies and consecutives samples in the same patients.

We investigated 159 isolates and Mycobacterium abscessus subsp abscessus accounted for the majority of the M. abscessus isolates (n=124,77.4%). We isolated the first M. abscessus subsp bolletii. Both cohort of cystic fibrosis and non-cystic fibrosis patients were predominantly isolated from Female. Our findings confirmed that Mycobacterium abscessus subsp abscessus (87.3%) were the dominant subspecies in CF patients. Genotypic markers for Clarithromycin and Amikacin had strong association to the phenotypic susceptibility, with PPV value of 91.3% and 98.7%. There was still unexplainable resistance, related to Linezolid, Amikacin and Ciprofloxacin that can possibly involve other genes that have not been analyzed or other cell mechanism are involved to produce resistance.