In vitro susceptibility of Mycobacterium abscessus complex and feasibility of standardizing treatment regimens.

OBJECTIVES: To determine the in vitro susceptibility of members of the Mycobacterium abscessus complex to routinely tested antibiotics and to an extended antibiotic panel. METHODS: Non-duplicate isolates for which susceptibility testing results were available were included in this study. Retrospective laboratory records were reviewed, including tigecycline susceptibility results, and testing was performed with additional drugs, including vancomycin, dalbavancin, telavancin, oritavancin, rifabutin, delafloxacin, eravacycline, clofazimine and bedaquiline using broth microdilution (Sensititre, Thermo Fisher). RESULTS: A total of 218 M. abscessus complex isolates were included for retrospective review, of which 151 were respiratory isolates. Of these 218 isolates, 211 were available for additional testing with the extended antibiotic panel. Of these, 146 were respiratory isolates. One isolate had a vancomycin MIC of 2 mg/L and MICs of all other isolates were >8 mg/L. All isolates had MICs of >8 mg/L for oritavancin, dalbavancin and telavancin. One isolate had a delafloxacin MIC of 4 mg/L and MICs of all other isolates were >8 mg/L. The MIC50/MIC90s of rifabutin, tigecycline, eravacycline, clofazimine and bedaquiline were 16/32, 0.5/1, 0.12/0.25, 0.12/0.25 and 0.06/0.12 mg/L, respectively. CONCLUSIONS: In vitro activity was demonstrated for clofazimine, bedaquiline and eravacycline, indicating potential for inclusion as standardized therapy for M. abscessus complex infections.

Delay in effective therapy in anidulafungin-resistant Candida tropicalis fungaemia: Potential for rapid prediction of antifungal resistance with whole-genome-sequencing.

OBJECTIVES: This study investigated the feasibility of using whole-genome sequencing (WGS) for the prediction of antifungal resistance in anidulafungin-resistant Candida tropicalis candidaemia isolates. METHODS: Next-generation sequencing was performed for three anidulafungin-resistant C. tropicalis isolates on an Illumina MiSeq system with in-house bioinformatics analysis. RESULTS: Mutations in Fks1p associated with anidulafungin resistance were identified. Other mutations associated with varying levels of phenotypic resistance to fluconazole were also identified. CONCLUSIONS: These data demonstrate the potential to predict antifungal resistance using WGS. With improving technology, real-time WGS may be used for tailoring effective antifungal therapy in patients with candidaemia.