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Volume 28, Number 7—July 2022

One Health Genomic Analysis of Extended-Spectrum β-Lactamase‒Producing Salmonella enterica, Canada, 2012‒2016

Amrita BharatComments to Author , Laura Mataseje, E. Jane Parmley, Brent P. Avery, Graham Cox, Carolee A. Carson, Rebecca J. Irwin, Anne E. Deckert, Danielle Daignault, David C. Alexander, Vanessa Allen, Sameh El Bailey, Sadjia Bekal, Greg J. German, David Haldane, Linda Hoang, Linda Chui, Jessica Minion, George Zahariadis, Richard J. Reid-Smith, and Michael R. Mulvey
Author affiliations: Public Health Agency of Canada, Winnipeg, Manitoba, Canada (A. Bharat, L. Mataseje, G. Cox, M.R. Mulvey); University of Manitoba, Winnipeg (A. Bharat, G. Cox, M.R. Mulvey); Public Health Agency of Canada, Guelph, Ontario, Canada (E.J. Parmley, B.P. Avery, C.A. Carson, R.J. Irwin, A.E. Deckert, R.J. Reid-Smith); University of Guelph, Guelph (E.J. Parmley); Public Health Agency of Canada, St. Hyacinthe, Quebec, Canada (D. Daignault); Cadham Provincial Laboratory, Winnipeg (D.C. Alexander); Public Health Ontario Laboratories, Toronto, Ontario, Canada (V. Allen); Horizon Health Network, Saint John, New Brunswick, Canada (S. El Bailey); Laboratoire de Santé Publique du Quebec, Sainte-Anne-de-Bellevue, Quebec, Canada (S. Bekal); Queen Elizabeth Hospital, Charlottetown, Prince Edward Island, Canada (G.J. German); Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada (D. Haldane); British Columbia Center for Disease Control, Vancouver, British Columbia, Canada (L. Hoang); Public Health Laboratory, Edmonton, Alberta, Canada (L. Chiu); University of Alberta, Edmonton (L. Chui); Roy Romanow Provincial Laboratory, Regina, Saskatchewan, Canada (J. Minion); Newfoundland and Labrador Public Health and Microbiology Laboratory, St. John’s, Newfoundland, Canada (G. Zahariadis)

Main Article

Table 4

Phenotypic susceptibility and genetic resistance determinants for 13 antimicrobial drugs in Salmonella sp. Canada

Antimicrobial drug Human source, n = 54
Animals/meat source, n = 41
No. resistant (%)* Genetic determinants† No. resistant (%)* Genetic determinants†
Amoxicillin/clavulanic acid

6 (14.6)
blaCMY-2 (n = 6)
54 (100)
blaCTX-M-1, blaCTX-M-3, blaCTX-M-9, blaCTX-M-14, blaCTX-M-15, blaCTX-M-55, blaCTX-M-65, blaSHV-2, blaSHV-5 (n = 54)

41 (100)
blaCTX-M-1, blaCTX-M-55, blaSHV-2, blaSHV-12 (n = 41)

1 (2.4)
mphA (n = 1)
29 (53.7)
floR, catA, catB, cmlA (n = 27)

7 (17.1)
floR (n = 5)
31 (57.4)
GyrA D87Y or D87G, qnrA1, qnrB1, qnrS1, aac(6')-Ib-cr (n = 31)

3 (7.3)
qnrB2, qnrS1 (n = 3)
54 (100)
blaCTX-M-1, blaCTX-M-3, blaCTX-M-9, blaCTX-M-14, blaCTX-M-15, blaCTX-M-55, blaCTX-M-65, blaSHV-2, blaSHV-5 (n = 54)

41 (100)
blaCTX-M-1, blaCTX-M-55, blaSHV-2, blaSHV-12 (n = 41)
1 (1.9)

7 (17.1)
blaCMY-2 (n = 6)
13 (24)
aac(3)-IIa, aac-(3)-IId, aac(3)-IVa, aac(3)-Vla, and rmtB (n = 25)

24 (58.5)
aac(3)-IId, aac(3)-Vla, aac(6')-Iy, and aac(6')-IIc (n = 23)
Nalidixic acid
20 (37)
GyrA D87Y or D87G, qnrS1 (n = 20)


35 (64.8)
sul1, sul2, sul3 (n = 35)

26 (63.4)
sul1, sul2, sul3 (n = 26)
28 (51.9)
aadA1, aadA2, ant(3”)-Ia, ant(3”)-Ib, aph(3”)-Ib, and strA (n = 31)

23 (56.1)
aadA1, aadA2, ant(3”)-Ia, ant(3”)-Ib, and strA (n = 29)
26 (48.1)
dfrA1, dfrA12, dfrA14, dfrA16, dfrA18, dfrA23 (n = 26)

12 (29.3)
dfrA1, dfrA14, drfA18 (n = 12)
Tetracycline 43 (79.6) tetA and tetB (n = 40) 21 (51.2) tetA, tetB, and tetD (n = 21)

*Where available, resistance was interpreted according to Clinical Laboratory Standards Institute breakpoints; for azithromycin, the National Antimicrobial Resistance Monitoring System NARMs breakpoint of 32 mg/L was used; for ciprofloxacin, both intermediate and full resistance were included. †n value in parentheses indicates number of isolates that contained >1 genetic determinant of resistance.

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  1. GBD 2017 Non-typhoidal Salmonella invasive disease collaborators. The global burden of non-typhoidal Salmonella invasive disease: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Infect Dis. 2019;19:131224.
  2. Roth  GA, Abate  D, Abate  KH, Abay  SM, Abbafati  C, Abbasi  N, et al.; GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392:173688. DOIPubMedGoogle Scholar
  3. Shane  AL, Mody  RK, Crump  JA, Tarr  PI, Steiner  TS, Kotloff  K, et al. 2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea. Clin Infect Dis. 2017;65:196373. DOIPubMedGoogle Scholar
  4. Bush  K. Past and present perspectives on β-lactamases. Antimicrob Agents Chemother. 2018;62:e0107618. DOIPubMedGoogle Scholar
  5. Karaiskos  I, Giamarellou  H. Carbapenem-sparing strategies for ESBL producers: when and how. Antibiotics (Basel). 2020;9:61. DOIPubMedGoogle Scholar
  6. Hernando-Amado  S, Coque  TM, Baquero  F, Martínez  JL. Defining and combating antibiotic resistance from One Health and Global Health perspectives. Nat Microbiol. 2019;4:143242. DOIPubMedGoogle Scholar
  7. Chicken Farms of Canada. Preventative use of category I antibiotics in the poultry and egg sectors, 2013 [cited 2020 Dec 19].
  8. Health Canada. Responsible use of medically important antimicrobials in animals. 2020. p. 1‒15 [cited 2020 Dec 18].
  9. Denisuik  AJ, Karlowsky  JA, Adam  HJ, Baxter  MR, Lagacé-Wiens  PRS, Mulvey  MR, et al.; Canadian Antimicrobial Resistance Alliance (CARA) and CANWARD. Dramatic rise in the proportion of ESBL-producing Escherichia coli and Klebsiella pneumoniae among clinical isolates identified in Canadian hospital laboratories from 2007 to 2016. J Antimicrob Chemother. 2019;74(Suppl 4):iv6471. DOIPubMedGoogle Scholar
  10. Kazmierczak  KM, de Jonge  BLM, Stone  GG, Sahm  DF. Longitudinal analysis of ESBL and carbapenemase carriage among Enterobacterales and Pseudomonas aeruginosa isolates collected in Europe as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance programme, 2013-17. J Antimicrob Chemother. 2020;75:116573. DOIPubMedGoogle Scholar
  11. Toy  T, Pak  GD, Duc  TP, Campbell  JI, El Tayeb  MA, Von Kalckreuth  V, et al. Multicountry distribution and characterization of extended-spectrum β-lactamase-associated Gram-negative bacteria from bloodstream infections in Sub-Saharan Africa. Clin Infect Dis. 2019;69(Suppl 6):S44958. DOIPubMedGoogle Scholar
  12. Sjölund-Karlsson  M, Howie  RL, Blickenstaff  K, Boerlin  P, Ball  T, Chalmers  G, et al. Occurrence of β-lactamase genes among non-Typhi Salmonella enterica isolated from humans, food animals, and retail meats in the United States and Canada. Microb Drug Resist. 2013;19:1917. DOIPubMedGoogle Scholar
  13. Sjölund-Karlsson  M, Rickert  R, Matar  C, Pecic  G, Howie  RL, Joyce  K, et al. Salmonella isolates with decreased susceptibility to extended-spectrum cephalosporins in the United States. Foodborne Pathog Dis. 2010;7:15039. DOIPubMedGoogle Scholar
  14. Sjölund-Karlsson  M, Howie  R, Krueger  A, Rickert  R, Pecic  G, Lupoli  K, et al. CTX-M-producing non-Typhi Salmonella spp. isolated from humans, United States. Emerg Infect Dis. 2011;17:979. DOIPubMedGoogle Scholar
  15. CIPARS. Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS), 2018: design and methods. 2020. p. 1–57 [cited 2022 May 3].
  16. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing (M100–ED29). Wayne (PA); The Institute; 2019. p. 1–321 [cited 2022 May 3].
  17. Mulvey  MR, Grant  JM, Plewes  K, Roscoe  D, Boyd  DA. New Delhi metallo-β-lactamase in Klebsiella pneumoniae and Escherichia coli, Canada. Emerg Infect Dis. 2011;17:1036. DOIPubMedGoogle Scholar
  18. Bankevich  A, Nurk  S, Antipov  D, Gurevich  AA, Dvorkin  M, Kulikov  AS, et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol. 2012;19:45577. DOIPubMedGoogle Scholar
  19. Wick  RR, Judd  LM, Gorrie  CL, Holt  KE. Unicycler: Resolving bacterial genome assemblies from short and long sequencing reads. PLOS Comput Biol. 2017;13:e1005595. DOIPubMedGoogle Scholar
  20. Bharat  A, Petkau  A, Avery  BP, Chen  JC, Folster  JP, Carson  CA, et al. Correlation between phenotypic and in silico detection of antimicrobial resistance in Salmonella enterica in Canada using Staramr. Microorganisms. 2022;10:292. DOIPubMedGoogle Scholar
  21. Zankari  E, Hasman  H, Cosentino  S, Vestergaard  M, Rasmussen  S, Lund  O, et al. Identification of acquired antimicrobial resistance genes. J Antimicrob Chemother. 2012;67:26404. DOIPubMedGoogle Scholar
  22. Zankari  E, Allesøe  R, Joensen  KG, Cavaco  LM, Lund  O, Aarestrup  FM. PointFinder: a novel web tool for WGS-based detection of antimicrobial resistance associated with chromosomal point mutations in bacterial pathogens. J Antimicrob Chemother. 2017;72:27648. DOIPubMedGoogle Scholar
  23. Petkau  A, Mabon  P, Sieffert  C, Knox  NC, Cabral  J, Iskander  M, et al. SNVPhyl: a single nucleotide variant phylogenomics pipeline for microbial genomic epidemiology. Microb Genom. 2017;3:e000116. DOIPubMedGoogle Scholar
  24. Guindon  S, Dufayard  J-F, Lefort  V, Anisimova  M, Hordijk  W, Gascuel  O. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst Biol. 2010;59:30721. DOIPubMedGoogle Scholar
  25. Mulvey  MR, Bharat  A, Boyd  DA, Irwin  RJ, Wylie  J. Characterization of a colistin-resistant Salmonella enterica 4,[5],12:i:- harbouring mcr-3.2 on a variant IncHI-2 plasmid identified in Canada. J Med Microbiol. 2018;67:16735. DOIPubMedGoogle Scholar
  26. Tate  H, Folster  JP, Hsu  C-H, Chen  J, Hoffmann  M, Li  C, et al. Comparative analysis of extended-spectrum-β-lactamase CTX-M-65‒producing Salmonella enterica serovar Infantis isolates from humans, food animals, and retail chickens in the United States. Antimicrob Agents Chemother. 2017;61:e0048817. DOIPubMedGoogle Scholar
  27. Sampei  G, Furuya  N, Tachibana  K, Saitou  Y, Suzuki  T, Mizobuchi  K, et al. Complete genome sequence of the incompatibility group I1 plasmid R64. Plasmid. 2010;64:92103. DOIPubMedGoogle Scholar
  28. Brown  AC, Chen  JC, Watkins  LKF, Campbell  D, Folster  JP, Tate  H, et al. CTX-M-65 Extended-spectrum β-lactamase‒producing Salmonella enterica serotype Infantis, United States. Emerg Infect Dis. 2018;24:228491. DOIPubMedGoogle Scholar
  29. Health Canada. Categorization of antimicrobial drugs based on importance in human medicine. 2020. p. 1‒9 [cited 2020 Dec 22].
  30. Peirano  G, Pitout  JDD. Extended-spectrum β-lactamase‒producing Enterobacteriaceae: update on molecular epidemiology and treatment options. Drugs. 2019;79:152941. DOIPubMedGoogle Scholar
  31. Zhang  C-Z, Ding  X-M, Lin  X-L, Sun  R-Y, Lu  Y-W, Cai  R-M, et al. The emergence of chromosomally located blaCTX-M-55 in Salmonella from foodborne animals in China. Front Microbiol. 2019;10:1268. DOIPubMedGoogle Scholar
  32. Wang  W, Zhao  L, Hu  Y, Dottorini  T, Fanning  S, Xu  J, et al. Epidemiological study on prevalence, serovar diversity, multidrug resistance, and CTX-M-type extended-spectrum β-lactamases of Salmonella spp. from patients with diarrhea, food of animal origin, and pets in several provinces of China. Antimicrob Agents Chemother. 2020;64:10. DOIPubMedGoogle Scholar
  33. Bevan  ER, Jones  AM, Hawkey  PM. Global epidemiology of CTX-M β-lactamases: temporal and geographical shifts in genotype. J Antimicrob Chemother. 2017;72:214555. DOIPubMedGoogle Scholar
  34. Franco  A, Leekitcharoenphon  P, Feltrin  F, Alba  P, Cordaro  G, Iurescia  M, et al. Emergence of a clonal lineage of multidrug-resistant ESBL-producing Salmonella Infantis transmitted from broilers and broiler meat to humans in Italy between 2011 and 2014. PLoS One. 2015;10:e0144802. DOIPubMedGoogle Scholar
  35. Alba  P, Leekitcharoenphon  P, Carfora  V, Amoruso  R, Cordaro  G, Di Matteo  P, et al. Molecular epidemiology of Salmonella Infantis in Europe: insights into the success of the bacterial host and its parasitic pESI-like megaplasmid. Microb Genom. 2020;6:e000365. DOIPubMedGoogle Scholar
  36. Lee  WWY, Mattock  J, Greig  DR, Langridge  GC, Baker  D, Bloomfield  S, et al. Characterization of a pESI-like plasmid and analysis of multidrug-resistant Salmonella enterica Infantis isolates in England and Wales. Microb Genom. 2021;7:000658. DOIPubMedGoogle Scholar
  37. Cartelle Gestal  M, Zurita  J, Paz Y Mino  A, Ortega-Paredes  D, Alcocer  I, Alcocer  I, et al. Characterization of a small outbreak of Salmonella enterica serovar Infantis that harbour CTX-M-65 in Ecuador. Braz J Infect Dis. 2016;20:4067. DOIPubMedGoogle Scholar
  38. Martínez-Puchol  S, Riveros  M, Ruidias  K, Granda  A, Ruiz-Roldán  L, Zapata-Cachay  C, et al. Dissemination of a multidrug resistant CTX-M-65 producer Salmonella enterica serovar Infantis clone between marketed chicken meat and children. Int J Food Microbiol. 2021;344:109109. DOIPubMedGoogle Scholar
  39. de Been  M, Lanza  VF, de Toro  M, Scharringa  J, Dohmen  W, Du  Y, et al. Dissemination of cephalosporin resistance genes between Escherichia coli strains from farm animals and humans by specific plasmid lineages. PLoS Genet. 2014;10:e1004776. DOIPubMedGoogle Scholar
  40. Zhang  W-H, Lin  X-Y, Xu  L, Gu  X-X, Yang  L, Li  W, et al. CTX-M-27 producing Salmonella enterica serotypes Typhimurium and Indiana are prevalent among food-producing animals in China. Front Microbiol. 2016;7:436. DOIPubMedGoogle Scholar
  41. Elnekave  E, Hong  SL, Lim  S, Hayer  SS, Boxrud  D, Taylor  AJ, et al. Circulation of plasmids harboring resistance genes to quinolones and/or extended-spectrum cephalosporins in multiple Salmonella enterica serotypes from swine in the United States. Antimicrob Agents Chemother. 2019;63:901. DOIPubMedGoogle Scholar
  42. Karanika  S, Karantanos  T, Arvanitis  M, Grigoras  C, Mylonakis  E. Fecal colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae and risk factors among healthy individuals: a systematic review and metaanalysis. Clin Infect Dis. 2016;63:3108. DOIPubMedGoogle Scholar
  43. Eshaghi  A, Zittermann  S, Bharat  A, Mulvey  MR, Allen  VG, Patel  SN. Importation of extensively drug-resistant Salmonella enterica serovar Typhi cases in Ontario, Canada. Antimicrob Agents Chemother. 2020;64:e570. DOIPubMedGoogle Scholar

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