FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
The Journal of antimicrobial chemotherapy2024; 80(2); 567-575; doi: 10.1093/jac/dkae448

Distinct molecular epidemiology of resistances to extended-spectrum cephalosporins and carbapenems in Enterobacter hormaechei in cats and dogs versus horses in France.

Abstract: Enterobacter hormaechei is an important pathogen in humans and animals, which, in addition to its intrinsic AmpC, can acquire a wide variety of genes conferring resistances to extended-spectrum cephalosporins (ESCs) and carbapenems (CPs). In France, human clinical outbreaks of E. hormaechei resistant to ESC or carbapenem were reported. Objective: To study E. hormaechei isolates from cats and dogs (=59) as well as from horses (n = 55) presenting a non-susceptible phenotype to beta-lactams in order to determine which clones, resistance genes and plasmids are circulating in France. Methods: E. hormaechei isolates (n = 114) were short-read sequenced and five isolates were long-read sequenced to better characterize the plasmids carrying ESC- and CP-resistance determinants. Phenotypes were characterized by antibiograms using the disc diffusion method. Results: A clear divergence in the molecular epidemiology was observed depending on the host. In cats and dogs, most of the isolates presented an overexpressed ampC gene or the blaCTX-M-15 gene carried by an IncHI2 plasmid, and eight isolates (8/59, 13.6%) presented the blaOXA-48 carbapenemase gene. Thirty-two isolates (32/59, 54.2%) belonged to the human high-risk clones ST78, ST114 and ST171. Contrarily, in horses, ESC resistance was mostly due to the blaSHV-12 and blaCTX-M-15 genes carried by an IncHI2 plasmid, and high-risk clones were rarely identified (5/55, 9.0%). Conclusions: Potential selection by antibiotic use (which is on an increasing trend in France for cats, dogs and horses), the dissemination capacities of both conjugative IncHI2 plasmids and high-risk clones, and possible transfers of resistant bacteria between humans and animals strongly indicate that E. hormaechei should be closely monitored.
© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.
Get Full Text
Publication Date: 2024-12-12 PubMed ID: 39665267PubMed Central: PMC11787895DOI: 10.1093/jac/dkae448Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This research investigates the molecular characteristics of antibiotic resistance in Enterobacter hormaechei isolated from cats, dogs, and horses in France, focusing on differences in the strains and resistance genes found in these animals, particularly regarding resistance to extended-spectrum cephalosporins (ESCs) and carbapenems (CPs).

Introduction and Background

  • Enterobacter hormaechei is a bacterial pathogen affecting both humans and animals.
  • It naturally possesses an enzyme called AmpC beta-lactamase but can also acquire genes that provide resistance to important antibiotics such as ESCs and CPs.
  • Escalating antibiotic resistance in E. hormaechei has been reported in human clinical outbreaks in France.
  • The study focuses on identifying how these resistant bacteria differ between animal hosts — specifically, cats and dogs versus horses — and the implications for antibiotic resistance spread.

Objectives

  • To analyze E. hormaechei isolates from pets (cats and dogs) and horses with reduced susceptibility to beta-lactam antibiotics.
  • To characterize the bacterial clones, resistance genes, and plasmids circulating in France within these animals.

Methods

  • A total of 114 E. hormaechei isolates were collected: 59 from cats and dogs, and 55 from horses.
  • Short-read whole-genome sequencing was performed on all isolates to study their genetic makeup.
  • Five selected isolates underwent long-read sequencing to more precisely analyze plasmids carrying resistance genes.
  • Antibiotic susceptibility was assessed using antibiograms through the disc diffusion method.

Key Findings

  • Molecular differences by host animal:
    • In cats and dogs:
      • Most isolates showed either overexpression of the intrinsic ampC gene or carried the blaCTX-M-15 gene, which confers extended-spectrum cephalosporin resistance.
      • The blaCTX-M-15 gene was mostly located on IncHI2 plasmids, which are mobile genetic elements capable of transferring resistance between bacteria.
      • Eight isolates (13.6%) carried the blaOXA-48 gene encoding carbapenem resistance.
      • More than half of these isolates (54.2%) corresponded to known human high-risk clones (ST78, ST114, ST171), known for spreading resistance.
    • In horses:
      • Resistance to ESCs was predominantly due to blaSHV-12 and blaCTX-M-15 genes, mostly on IncHI2 plasmids.
      • High-risk human clones were rare, only detected in 9.0% of isolates.

Interpretation and Implications

  • The significant difference in molecular epidemiology between companion animals (cats and dogs) and horses indicates distinct reservoirs and transmission pathways of resistance genes.
  • High-risk human-associated bacterial clones being prevalent in cats and dogs suggests a potential for cross-species transmission between humans and pets.
  • The recurring presence of IncHI2 plasmids, known to spread resistance genes effectively, highlights a concerning mechanism for dissemination across bacterial populations.
  • Antibiotic use in animals, which is rising in France, may be selecting for resistant strains, raising the risk of further resistance development and spread.
  • Close monitoring and surveillance of E. hormaechei are advised to better control the spread of these resistant bacteria in both veterinary and human medicine settings.

Conclusions

  • The study reveals host-specific differences in the molecular epidemiology and resistance mechanisms of E. hormaechei in France.
  • The findings emphasize the importance of monitoring antibiotic resistance in animal pathogens due to their potential impact on human health.
  • Strategies to mitigate the spread should consider antibiotic stewardship in veterinary medicine and efforts to understand the epidemiology of plasmid-mediated and clonal dissemination of resistance.

Cite This Article

APA
Haenni M, Châtre P, Drapeau A, Cazeau G, Troncy J, François P, Madec JY. (2024). Distinct molecular epidemiology of resistances to extended-spectrum cephalosporins and carbapenems in Enterobacter hormaechei in cats and dogs versus horses in France. J Antimicrob Chemother, 80(2), 567-575. https://doi.org/10.1093/jac/dkae448

Publication

The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
NlmUniqueID: 7513617
Country: England
Language: English
Volume: 80
Issue: 2
Pages: 567-575

Researcher Affiliations

Haenni, Marisa
  • ANSES-Université de Lyon, Unité Antibiorésistance et Virulence Bactériennes, Lyon, France.
Châtre, Pierre
  • ANSES-Université de Lyon, Unité Antibiorésistance et Virulence Bactériennes, Lyon, France.
Drapeau, Antoine
  • ANSES-Université de Lyon, Unité Antibiorésistance et Virulence Bactériennes, Lyon, France.
Cazeau, Géraldine
  • ANSES-Université de Lyon, Unité Epidémiologie et Appui à la Surveillance, Lyon, France.
Troncy, Jonathan
  • ANSES-Université de Lyon, Unité Antibiorésistance et Virulence Bactériennes, Lyon, France.
François, Pauline
  • ANSES-Université de Lyon, Unité Antibiorésistance et Virulence Bactériennes, Lyon, France.
Madec, Jean-Yves
  • ANSES-Université de Lyon, Unité Antibiorésistance et Virulence Bactériennes, Lyon, France.

MeSH Terms

  • Animals
  • Horses
  • France / epidemiology
  • Cats
  • Enterobacteriaceae Infections / veterinary
  • Enterobacteriaceae Infections / epidemiology
  • Enterobacteriaceae Infections / microbiology
  • Cephalosporins / pharmacology
  • Dogs
  • Anti-Bacterial Agents / pharmacology
  • Enterobacter / drug effects
  • Enterobacter / genetics
  • Enterobacter / isolation & purification
  • Carbapenems / pharmacology
  • Plasmids / analysis
  • Molecular Epidemiology
  • Microbial Sensitivity Tests
  • beta-Lactamases / genetics
  • Cat Diseases / microbiology
  • Cat Diseases / epidemiology
  • Sequence Analysis, DNA
  • Dog Diseases / microbiology
  • Dog Diseases / epidemiology
  • Horse Diseases / microbiology
  • Horse Diseases / epidemiology

Grant Funding

  • ANSES

References

This article includes 46 references
  1. Davin-Regli A, Lavigne J-P, Pagès J-M. spp. update on taxonomy, clinical aspects, and emerging antimicrobial resistance.. Clin Microbiol Rev 2019; 32: e00002-19.
    doi: 10.1128/CMR.00002-19pmc: PMC6750132pubmed: 31315895google scholar: lookup
  2. Beyrouthy R, Barets M, Marion E. Novel lineage as leading cause of nosocomial outbreak involving carbapenemase-producing strains.. Emerg Infect Dis 2018; 24: 1505–15.
    doi: 10.3201/eid2408.180151pmc: PMC6056098pubmed: 30014838google scholar: lookup
  3. Chavda KD, Chen L, Fouts Derrick E. Comprehensive genome analysis of carbapenemase-producing spp.: new insights into phylogeny, population structure, and resistance mechanisms.. mBio 2016; 10: 1128.
    doi: 10.1128/mbio.02093-16pmc: PMC5156309pubmed: 27965456google scholar: lookup
  4. Yeh T-K, Lin H-J, Liu P-Y. Antibiotic resistance in .. Int J Antimicrob Agents 2022; 60:106650.
    doi: 10.1016/j.ijantimicag.2022.106650pubmed: 35934231google scholar: lookup
  5. Cardoso B, Sellera FP, Sano E. Phylogenomic analysis of CTX-M-15-producing belonging to the high-risk ST78 from animal infection: another successful One Health clone?. J Glob Antimicrob Resist 2022; 29: 113–5.
    doi: 10.1016/j.jgar.2022.02.010pubmed: 35189373google scholar: lookup
  6. Haenni M, Saras E, Ponsin C. High prevalence of international ESBL CTX-M-15-producing ST114 clone in animals.. J Antimicrob Chemother 2016; 71: 1497–500.
    doi: 10.1093/jac/dkw006pubmed: 26850718google scholar: lookup
  7. Harada K, Shimizu T, Mukai Y. Phenotypic and molecular characterization of antimicrobial resistance in spp. isolates from companion animals in Japan.. PLoS One 2017; 12: e0174178.
    doi: 10.1371/journal.pone.0174178pmc: PMC5362103pubmed: 28328967google scholar: lookup
  8. Roberts LW, Harris PNA, Forde BM. Integrating multiple genomic technologies to investigate an outbreak of carbapenemase-producing .. Nat Commun 2020; 11: 466.
    doi: 10.1038/s41467-019-14139-5pmc: PMC6981164pubmed: 31980604google scholar: lookup
  9. Hadjirin NF, van Tonder AJ, Blane B. Dissemination of carbapenemase-producing Enterobacterales in Ireland from 2012 to 2017: a retrospective genomic surveillance study.. Microb Genom 2023; 9: mgen000924.
    doi: 10.1099/mgen.0.000924pmc: PMC10132065pubmed: 36916881google scholar: lookup
  10. Yousfi M, Touati A, Muggeo A. Clonal dissemination of OXA-48-producing Enterobacter cloacae isolates from companion animals in Algeria.. J Glob Antimicrob Res 2018; 12: 187–91.
    doi: 10.1016/j.jgar.2017.10.007pubmed: 29042339google scholar: lookup
  11. Pulss S, Stolle I, Stamm I. Multispecies and clonal dissemination of OXA-48 carbapenemase in Enterobacteriaceae from companion animals in Germany, 2009–2016.. Front Microbiol 2018; 9: 1265.
    doi: 10.3389/fmicb.2018.01265pmc: PMC6010547pubmed: 29963026google scholar: lookup
  12. Donà V, Nordmann P, Kittl S. Emergence of OXA-48-producing in a Swiss companion animal clinic and their genetic relationship to clinical human isolates.. J Antimicrob Chemother 2023; 78: 2950–60.
    doi: 10.1093/jac/dkad337pubmed: 37923369google scholar: lookup
  13. Kobs VC, de Medeiros F, Fernandes PP. Healthcare-associated NDM-1-producing subsp. clone ST136 emerging as pathogen of companion animals in Brazil.. J Antimicrob Chemother 2023; 78: 1553–6.
    doi: 10.1093/jac/dkad124pubmed: 37144593google scholar: lookup
  14. Daniels JB, Chen L, Grooters SV. complex sequence type 171 isolates expressing KPC-4 carbapenemase recovered from canine patients in Ohio.. Antimicrob Agents Chemother 2018; 62: e01161-18.
    doi: 10.1128/AAC.01161-18pmc: PMC6256759pubmed: 30249699google scholar: lookup
  15. Leelapsawas C, Sroithongkham P, Payungporn S. First report of -carrying IncX3 plasmids in multidrug-resistant and recovered from canine and feline opportunistic infections.. Microbiol Spectr 2024; 12: e0358923.
    doi: 10.1128/spectrum.03589-23pmc: PMC10913469pubmed: 38319115google scholar: lookup
  16. Sadek M, Nariya H, Shimamoto T. First genomic characterization of and -coharbouring isolated from food of animal origin.. Pathogens 2020; 9: 687.
    doi: 10.3390/pathogens9090687pmc: PMC7558541pubmed: 32842587google scholar: lookup
  17. Li R, Liu Z, Li Y. Characterization of -positive Enterobacteriaceae reveals the clonal dissemination of coharboring and along the pork production chain.. Int J Food Microbiol 2022; 372: 109692.
    doi: 10.1016/j.ijfoodmicro.2022.109692pubmed: 35504161google scholar: lookup
  18. Macesic N, Blakeway LV, Stewart JD. Silent spread of mobile colistin resistance gene on IncHI2 ‘superplasmids’ in clinical carbapenem-resistant Enterobacterales.. Clin Microbiol Infect 2021; 27: 1856.e7–e13.
    doi: 10.1016/j.cmi.2021.04.020pubmed: 33915285google scholar: lookup
  19. Algarni S, Gudeta DD, Han J. Genotypic analyses of IncHI2 plasmids from enteric bacteria.. Sci Rep 2024; 14: 9802.
    doi: 10.1038/s41598-024-59870-2pmc: PMC11058233pubmed: 38684834google scholar: lookup
  20. Lumbreras-Iglesias P, de Toro M, Vázquez X. High-risk international clones ST66, ST171 and ST78 of Enterobacter cloacae complex causing blood stream infections in Spain and carrying with or without .. J Infect Public Health 2023; 16: 272–9.
    doi: 10.1016/j.jiph.2022.12.015pubmed: 36621205google scholar: lookup
  21. Girlich D, Poirel L, Nordmann P. Clonal distribution of multidrug-resistant .. Diagn Microbiol Infect Dis 2015; 81: 264–8.
    doi: 10.1016/j.diagmicrobio.2015.01.003pubmed: 25680336google scholar: lookup
  22. Pot M, Guyomard-Rabenirina S, Couvin D. Dissemination of extended-spectrum-β-lactamase-producing complex from a hospital to the nearby environment in Guadeloupe (French West Indies): ST114 lineage coding for a successful IncHI2/ST1 plasmid.. Antimicrob Agents Chemother 2021; 65: e02146-20.
    doi: 10.1128/AAC.02146-20pmc: PMC8092524pubmed: 33361294google scholar: lookup
  23. Haenni M, Boulouis HJ, Lagrée AC. Enterobacterales high-risk clones and plasmids spreading and genes within and between hospitalized dogs and their environment.. J Antimicrob Chemother 2022; 77: 2754–62.
    doi: 10.1093/jac/dkac268pubmed: 35983589google scholar: lookup
  24. Emeraud C, Petit C, Gauthier L. Emergence of VIM-producing complex in France between 2015 and 2018.. J Antimicrob Chemother 2022; 77: 944–51.
    doi: 10.1093/jac/dkab471pubmed: 35045171google scholar: lookup
  25. Dortet L, Cuzon G, Ponties V. Trends in carbapenemase-producing Enterobacteriaceae, France, 2012 to 2014.. Euro Surveill 2017; 22: 30461.
    doi: 10.2807/1560-7917.ES.2017.22.6.30461pmc: PMC5316908pubmed: 28205502google scholar: lookup
  26. Rezzoug I, Emeraud C, Rodriguez C. Regional dissemination of NDM-1 producing ST1740, with a subset of strains co-producing VIM-4 or IMP-13, France, 2019 to 2022.. Euro Surveill 2024; 29: 2300521.
    doi: 10.2807/1560-7917.ES.2024.29.11.2300521pmc: PMC10941310pubmed: 38487887google scholar: lookup
  27. . French Surveillance Network for Antimicrobial Resistance in Bacteria From Diseased Animals.. .
  28. Magiorakos AP, Srinivasan A, Carey RB. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance.. Clin Microbiol Infect 2012; 18: 268–81.
    doi: 10.1111/j.1469-0691.2011.03570.xpubmed: 21793988google scholar: lookup
  29. Saidani M, Messadi L, Chaouechi A. High genetic diversity of Enterobacteriaceae clones and plasmids disseminating resistance to extended-spectrum cephalosporins and colistin in healthy chicken in Tunisia.. Microb Drug Resist 2019; 25: 1507–13.
    doi: 10.1089/mdr.2019.0138pubmed: 31329501google scholar: lookup
  30. Wagh ST, Razvi NA. Marascuilo method of multiple comparisons (an analytical study of caesarean section delivery).. Int J Contemp Med 2016; 3: 1137–40.
  31. Qiu X, Ye K, Ma Y. Genome sequence-based species classification of complex: a study among clinical isolates.. Microbiol Spectr 2024; 12: e0431223.
    doi: 10.1128/spectrum.04312-23pmc: PMC11237491pubmed: 38687068google scholar: lookup
  32. Jacoby GA. Ampc beta-lactamases.. Clin Microbiol Rev 2009; 22: 161–82.
    doi: 10.1128/CMR.00036-08pmc: PMC2620637pubmed: 19136439google scholar: lookup
  33. Choi S-H, Lee Jung E, Park Su J. Emergence of antibiotic resistance during therapy for infections caused by Enterobacteriaceae producing AmpC β-lactamase: implications for antibiotic use.. Antimicrob Agents Chemother 2008; 52: 995–1000.
    doi: 10.1128/AAC.01083-07pmc: PMC2258504pubmed: 18086837google scholar: lookup
  34. . Sales Survey of Veterinary Medicinal Products Containing Antimicrobials in France in 2022.. .
  35. Boattini M, Bianco G, Llorente LI. Enterobacterales carrying chromosomal AmpC β-lactamases in Europe (EuESCPM): epidemiology and antimicrobial resistance burden from a cohort of 27 hospitals, 2020–2022.. Int J Antimicrob Agents 2024; 63: 107115.
    doi: 10.1016/j.ijantimicag.2024.107115pubmed: 38367844google scholar: lookup
  36. Barceló IM, Escobar-Salom M, Jordana-Lluch E. Filling knowledge gaps related to AmpC-dependent β-lactam resistance in .. Sci Rep 2024; 14: 189.
    doi: 10.1038/s41598-023-50685-1pmc: PMC10762043pubmed: 38167986google scholar: lookup
  37. Allen JL, Doidge NP, Bushell RN. Healthcare-associated infections caused by chlorhexidine-tolerant carrying a promiscuous IncHI2 multi-drug resistance plasmid in a veterinary hospital.. PLoS One 2022; 17: e0264848.
    doi: 10.1371/journal.pone.0264848pmc: PMC8929579pubmed: 35298517google scholar: lookup
  38. Gao G, He W, Jiao Y. The origin and evolution of IncF33 plasmids based on large-scale data sets.. mSystems 2023; 8: e0050823.
    doi: 10.1128/msystems.00508-23pmc: PMC10654068pubmed: 37750716google scholar: lookup
  39. Kang HY, Kim KY, Kim J. Distribution of conjugative-plasmid-mediated 16S rRNA methylase genes among amikacin-resistant Enterobacteriaceae isolates collected in 1995 to 1998 and 2001 to 2006 at a university hospital in South Korea and identification of conjugative plasmids mediating dissemination of 16S rRNA methylase.. J Clin Microbiol 2008; 46: 700–6.
    doi: 10.1128/JCM.01677-07pmc: PMC2238143pubmed: 18094126google scholar: lookup
  40. Borjesson S, Greko C, Myrenas M. A link between the newly described colistin resistance gene and clinical Enterobacteriaceae isolates carrying from horses in Sweden.. J Glob Antimicrob Resist 2020; 20: 285–9.
    doi: 10.1016/j.jgar.2019.08.007pubmed: 31494305google scholar: lookup
  41. Aoki K, Harada S, Yahara K. Molecular characterization of IMP-1-producing Complex isolates in Tokyo.. Antimicrob Agents Chemother 2018; 62: e02091-17.
    doi: 10.1128/AAC.02091-17pmc: PMC5826111pubmed: 29311089google scholar: lookup
  42. Chavda KD, Westblade LF, Satlin MJ. First report of - and 9-coharboring species isolated from a pediatric patient.. mSphere 2019; 4: e00629-19.
    doi: 10.1128/mSphere.00629-19pmc: PMC6739498pubmed: 31511372google scholar: lookup
  43. Soliman AM, Maruyama F, Zarad HO. Emergence of a multidrug-resistant clinical isolate from Egypt co-harboring and .. Microorganisms 2020; 8: 595.
    doi: 10.3390/microorganisms8040595pmc: PMC7232449pubmed: 32325973google scholar: lookup
  44. Izdebski R, Biedrzycka M, Urbanowicz P. Genome-based epidemiologic analysis of VIM/IMP carbapenemase-producing spp., Poland.. Emerg Infect Dis 2023; 29: 1618.
    doi: 10.3201/eid2908.230199pmc: PMC10370858pubmed: 37486192google scholar: lookup
  45. Haenni M, Métayer V, Lupo A. Spread of the /IncL plasmid within and between dogs in city parks, France.. Microbiol Spectr 2022; 10: e0040322.
    doi: 10.1128/spectrum.00403-22pmc: PMC9241947pubmed: 35638816google scholar: lookup
  46. Izdebski R, Baraniak A, Herda M. MLST reveals potentially high-risk international clones of Enterobacter cloacae.. J Antimicrob Chemother 2015; 70: 48–56.
    doi: 10.1093/jac/dku359pubmed: 25216820google scholar: lookup

Citations

This article has been cited 1 times.
  1. De Maayer P, Green T, Jordan S, Smits THM, Coutinho TA. Pan-genome analysis of the Enterobacter hormaechei complex highlights its genomic flexibility and pertinence as a multidrug resistant pathogen. BMC Genomics 2025 Apr 26;26(1):408.
    doi: 10.1186/s12864-025-11590-1pubmed: 40287657google scholar: lookup
Subscribe to our newsletter
Join 99,911 horse owners like you who receive our email updates on horse health and nutrition.