title: Using whole-genome sequencing to determine appropriate streptomycin epidemiological cutoffs for Salmonella and Escherichia coli.
abstract: For Enterobacteriaceae such as Salmonella spp. and Escherichia coli, no unified interpretive resistance criteria exist for streptomycin, an epidemiologically important antibiotic. As part of the National Antimicrobial Resistance Monitoring System, we had previously used a minimum inhibitory concentration of ≥ 64 μg mL(-1) as an epidemiological cutoff value (ECV) to define non-wild-type isolates. To identify whether this ECV correlated with genetic determinants of resistance, we performed whole-genome sequencing of 463 Salmonella and E. coli isolates to identify streptomycin resistance genotypes. From this analysis, we found that using a streptomycin resistance breakpoint of ≥ 64 μg mL(-1) classified over 20% of strains possessing aadA or strA/strB resistance genes as wild-type. Therefore, to improve the concordance between genotypic and phenotypic data, we propose reducing the phenotypic cutoff values to ≥ 32 μg mL(-1) for both Salmonella and E. coli, to be used widely as ECVs to categorize non-wild-type isolates.
authors.affiliation: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, US Food and Drug Administration, 8401 Muirkirk Rd, Laurel, MD 20708, USA gregory.tyson@fda.hhs.gov.
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Tyson
authors.affiliation: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, US Food and Drug Administration, 8401 Muirkirk Rd, Laurel, MD 20708, USA.
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.affiliation: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, US Food and Drug Administration, 8401 Muirkirk Rd, Laurel, MD 20708, USA.
authors.forename: Sherry
authors.initials: S
authors.lastname: Ayers
authors.affiliation: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, US Food and Drug Administration, 8401 Muirkirk Rd, Laurel, MD 20708, USA.
authors.forename: Patrick F
authors.initials: PF
authors.lastname: McDermott
authors.affiliation: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, US Food and Drug Administration, 8401 Muirkirk Rd, Laurel, MD 20708, USA.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D004927:Escherichia coli Infections / Q000453:epidemiology; D016680:Genome, Bacterial / Q000235:genetics; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D008826:Microbial Sensitivity Tests / Q000592:standards*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012475:Salmonella / Q000187:drug effects / Q000235:genetics*; D012481:Salmonella Infections, Animal / Q000453:epidemiology; D013307:Streptomycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D013307:Streptomycin
keywords: E. coli; Salmonella; genotyping; resistance; streptomycin; whole-genome sequencing