Background: M. abscessus (Mab) is a highly antibiotic resistant opportunistic pathogen causing clinically challenging infections in patients with preexisting lung diseases or under immunosuppression. Hence, reliable antibiotic susceptibility data is required for effective treatment. Aims of this study were to investigate (i) the congruence of genotypic and phenotypic antimicrobial susceptibility testing, (ii) the relationship between resistance profile and clinical course, as well as (iii) the phylogenetic relations of Mab in a German patient cohort. Materials/methods: A total of 39 isolates from 29 patients infected or colonized with Mab underwent genotypic and phenotypic drug susceptibility testing. Clinical data were correlated to susceptibility data. Phylogenetic analysis was performed by means of whole genome sequencing (WGS) and single nucleotide polymorphism (SNP) analysis. Results: Macrolide resistance was mainly mediated by functional Erm (41) methyltransferases (T28 sequevars) in M. abscessus subsp. abscessus (n=25) and M. abscessus subsp. bolletii (n=2). It was significantly associated with impaired culture conversion (p=0.02). According to the core SNP phylogeny, we identified three clusters of closely related isolates with SNP distances below 25. Representatives of all circulating global clones (Absc. 1, Absc. 2 and Mass. 1) were identified in our cohort. However, we could not determine evidence for in-hospital interhuman transmission from clinical data. Conclusions: In our patient cohort, we identified three Mab clusters with closely related isolates and representatives of the previously described international clusters, but no human-to-human in-hospital transmission. Macrolide and aminoglycoside susceptibility data are critical for therapeutic decision-making in Mab infections.

Phenotypic (Sensititre Myco, pDST) and genotypic drug susceptibility testing (GenoType NTM DR, gDST) in M. avium complex (MAC) have become available as standardized assays, but comparable data is needed. This study aimed to investigate the phenotypic and genotypic drug susceptibility patterns in MAC clinical isolates. Methods: Overall, 98 isolates from 85 patients were included. pDST and gDST were performed on all isolates and results compared regarding specificity and sensitivity using pDST as a reference method. The impact of drug instability on pDST results was studied using a biological assay over 14 days. In addition, the evolution of antimicrobial resistance was investigated in sequential isolates of 13 patients. Results: Macrolide resistance was rare, 1.2% (95% CI 0.7-7.3) of isolates in the base cohort. No aminoglycoside resistances were found, but 14.1% of the studied isolates (95% CI 7.8-23.8) showed intermediate susceptibility. The GenoType NTM DR identified two out of four macrolide-resistant isolates. Antibiotic stability was demonstrated to be poor in rifampicin, rifabutin, and doxycycylin. Conclusions: pDST results in NTM for unstable antibiotics must be interpreted with care. A combination of pDST and gDST will be useful for the guidance of antimicrobial therapy in MAC-disease.

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