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Investigating the resistance rate and transmission of Mycobacterium abscessus among cystic fibrosis and non-cystic fibrosis patients

M Dohál(2) V Dvoráková(3) M Pinková(3) J Amlerová(4) M Schwarz(5) A Spitaleri(6,7) F di Marco(6) J Hnilicová(5,8) E Gondáš(9) E M Rasmussen(1) I Porvazník(10,11) I Solovic(10,11) D M Cirillo(6) J Mokrý(9)

1:International Reference laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, Denmark; 2:Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Bratislava, Slovakia; 3:National Institute of Public Health, Prague, Czech Republic; 4:Charles University, Faculty of Medicine in Pilsen, Faculty hospital, Pilsen, Czech Republic; 5:Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic; 6:Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy; 7:Vita-Salute San Raffaele University, Milan, Italy; 8:Department of Genetics and Microbiology, Faculty of Science, Charles University, Prague, Czech Republic; 9:Department of Pharmacology, Jessenius Faculty of Medicine in Martin, Comenius University, Bratislava, Slovakia; 10:National Institute of Tuberculosis, Lung Diseases and Thoracic Surgery, Vyšné Hágy, Slovakia; 11:Faculty of Health, Catholic University, Ružomberok, Slovakia

Mycobacterium (M.) abscessus is the most prevalent and clinically relevant rapidly growing NTM characterized for its capacity to induce severe pulmonary disease, which can be devastating for individuals with cystic fibrosis (CF). Moreover, the presence of this bacteria before the transplant may be a contraindation due to concerns for increased morbidity, mortality, and risk of post-transplant transmission. Hence, investigations into the epidemiology and transmission of M. abscessus and accurate antibiotic susceptibility data are essential for effective treatment of infections caused by this pathogen. This retrospective nationwide study included all clinical M. abscessus isolates (n=59) from 29 patients. Whole genome sequencing (WGS) was performed to identify clusters and classify isolates into predominant circulating clones (DCC). Subspecies identification of unique isolates showed subspecies abscessus as the most prevalent (65.5%). 65.5% of all isolates were resistant to at least 3 antibiotics tested. Utilizing WGS to evaluate genotypic drug sensitivity to macrolides and aminoglycosides revealed 100% sensitivity and specificity, when compared to the GenoType NTM-DR test. When compared to phenotypic sensitivity testing, the results showed 100% sensitivity and 68.75% specificity for macrolides, and 100% sensitivity and 95.83% specificity for aminoglycosides. WGS identified 7 clusters (including two cross-border) comprising CF and non-CF patients, with a total clustering rate of 48.3%. Furthermore, we identified representatives of all major DCCs. The results shown high discriminatory power of WGS in molecular-epidemiology of M. abscessus and provide supporting evidence of direct or indirect cross-transmission of subspecies massiliense among both CF and non-CF patients.

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