In vitro susceptibility patterns for slowly growing non-tuberculous mycobacteria in the USA from 2018 to 2022.

BACKGROUND: Treatment of slowly growing non-tuberculous mycobacteria (SGM) is challenging. In vitro antimicrobial susceptibility testing (AST) is needed to optimize a multidrug regimen but requires weeks to result. Aggregated AST patterns, or an antibiogram, of SGM would be helpful to providers. OBJECTIVES: We aggregated and analysed human SGM isolates sent to our laboratory from across the USA between 2018 and 2022 to describe their in vitro susceptibility patterns and construct an antibiogram. METHODS: SGM isolates' species/subspecies and mutations in rrs or rrl were identified by a line probe assay. AST was done primarily by broth microdilution and interpreted using the latest CLSI guideline. Mutational and AST results for SGM with ≥15 isolates were collated and analysed with descriptive statistics. RESULTS: There were 32 different species/subspecies of SGM from 10 131 isolates between January 2018 and December 2022 from across the USA, 80% of which were from organisms in Mycobacterium avium complex (MAC). Most specimens were sputum and came from Florida (2892). MAC ranged from 94% to 100% susceptible to clarithromycin, 64% to 91% to amikacin, 2% to 31% to linezolid, and 4% to 41% to moxifloxacin. Non-MAC SGM ranged from 82% to 100% susceptible to clarithromycin, 49% to 100% to amikacin, and 76% to 100% to rifabutin, but susceptibilities to other antimicrobials varied widely. WT rrs and rrl predicted >96% of phenotypic non-resistance to amikacin and clarithromycin, respectively, whereas mutant genotypes predicted >90% of phenotypic resistance. CONCLUSIONS: Most SGM are likely to be susceptible to clarithromycin and amikacin, complementing their treatment guidance by mycobacterial experts. Molecular identification of resistant genotypes is accurate and helpful. This antibiogram for SGM will help providers.

In vitro susceptibility patterns for rapidly growing nontuberculous mycobacteria in the United States.

Antimicrobial susceptibility testing for rapidly growing mycobacteria (RGM) is uncommon or only performed in large reference laboratories. Here we developed a cumulative antibiogram for 14 RGM using the largest sample size to date (N = 3860). All RGM showed 82% to 100% susceptibility to amikacin. Mycobacterium abscessus showed low percentages of susceptibility to most antimicrobials; of antimicrobials without interpretations, the minimum inhibitory concentration-90 for clofazimine was low (≤0.5mg/L). All three subspecies had ≤2.6% rrl resistance mutations, however intact erm(41) was detected in 70% to100% of M. abscessus abscessus and bolletii. Mycobacterium chelonae had a similar susceptibility pattern to M. abscessus subsp. massiliense and Mycobacterium immunogenum except that it was susceptible to tobramycin (87%). Mycobacterium fortuitum complex and similar organisms showed higher frequency of susceptibility to fluoroquinolones, beta-lactams, linezolid, and trimethoprim/sulfamethoxazole. Although relatively small published RGM antibiograms showed substantial variance, a comprehensive antibiogram can help influence treatment and monitoring patterns of resistance.

Population Genomics and Inference of Mycobacterium avium Complex Clusters in Cystic Fibrosis Care Centers, United States.

Mycobacterium avium complex (MAC) species constitute most mycobacteria infections in persons with cystic fibrosis (CF) in the United States, but little is known about their genomic diversity or transmission. During 2016-2020, we performed whole-genome sequencing on 364 MAC isolates from 186 persons with CF from 42 cystic fibrosis care centers (CFCCs) across 23 states. We compared isolate genomes to identify instances of shared strains between persons with CF. Among persons with multiple isolates sequenced, 15/56 (27%) had >1 MAC strain type. Genomic comparisons revealed 18 clusters of highly similar isolates; 8 of these clusters had patients who shared CFCCs, which included 27/186 (15%) persons with CF. We provide genomic evidence of highly similar MAC strains shared among patients at the same CFCCs. Polyclonal infections and high genetic similarity between MAC isolates are consistent with multiple modes of acquisition for persons with CF to acquire MAC infections.

Population Genomics of Mycobacterium abscessus from U.S. Cystic Fibrosis Care Centers.

Rationale:Mycobacterium abscessus is a significant threat to individuals with cystic fibrosis (CF) because of innate drug resistance and potential transmission between patients. Recent studies described global dominant circulating clones of M. abscessus, but detailed genomic surveys have not yet been described for the United States. Objectives: We examined the genetic diversity of respiratory M. abscessus isolates from U.S. patients with CF and evaluated the potential for transmission events within CF Care Centers. Methods: Whole-genome sequencing was performed on 558 M. abscessus isolates from 266 patients with CF attending 48 CF Care Centers in 28 U.S. states as part of a nationwide surveillance program. U.S. isolates were also compared with 64 isolate genomes from 13 previous studies to evaluate the prevalence of recently described dominant circulating clones. Results: More than half of study patients with CF and M. abscessus had isolates within four dominant clones; two clones of M. abscessus subspecies (subsp.) abscessus (MAB) and two clones of M. abscessus subsp. massiliense (MMAS). Acquired drug resistance mutations for aminoglycosides and macrolides were rare in the isolate population, and they were not significantly enriched in dominant clones compared with unclustered isolates. For a subset of 55 patients, there was no relationship between dominant clones and diagnosis of active lung disease (P = 1.0). Twenty-nine clusters of genetically similar MAB isolates and eight clusters of genetically similar MMAS isolates were identified. Overall, 28 of 204 (14%) patients with MAB and 15 of 64 (23%) patients with MMAS had genetically isolates similar to those of at least one other patient at the same CF Care Center. Genetically similar isolates were also found between 60 of 204 (29%) patients with MAB and 19 of 64 (30%) patients with MMAS from different geographic locations. Conclusions: Our study reveals the predominant genotypes of M. abscessus and frequency of shared strains between patients in U.S. CF Care Centers. Integrated epidemiological and environmental studies would help to explain the widespread presence of dominant clones in the United States, including the potential for broad distribution in the environment. Single site studies using systematic, evidence-based approaches will be needed to establish the contributions of health care-associated transmission versus shared environmental exposures.