Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 27, Number 2—February 2021
Research

Spread of Multidrug-Resistant Rhodococcus equi, United States

Sonsiray Álvarez-NarváezComments to Author , Steeve Giguère1, Noah Cohen, Nathan Slovis, and José A. Vázquez-BolandComments to Author 
Author affiliations: University of Georgia, Athens, Georgia, USA (S. Álvarez-Narváez, S. Giguère); Texas A&M University, College Station, Texas, USA (N. Cohen); Hagyard Equine Medical Institute, Lexington, Kentucky, USA (N. Slovis); University of Edinburgh, Edinburgh, Scotland, UK (J.A. Vázquez-Boland)

Main Article

Table

Effect of absence of tetRA(33) determinant from pRErm46 plasmid on R. equi susceptibility to tetracycline and doxycycline, determined on macrolide-resistant isolates collected during 2012–2017*

Antibiotic
 pRErm46
pRErm46 ΔC1I-tetRA(33)
Phenotype†
 MIC, μg/mL‡
 Phenotype
 MIC, μg/mL
Tetracycline Resistant (100)§ 21.33 (8–48)¶ Susceptible (100)§ 1.97 (0.38–3)¶
Doxycycline Susceptible (100) 3.35 (0.75–6)** Susceptible (100) 1.06 (0.25–3)**

*Susceptibility data to other relevant antimicrobials are shown in Appendix Table 2).
†Determined by disk diffusion technique. Isolate percentage shown in parenthesis. Zone diameter susceptibility breakpoints based on Clinical and Laboratory Standards Institute interpretive criteria for Staphylococcus aureus, routinely used for R. equi susceptibility testing in the absence of specific approved criteria for this species (11,16). 
‡Minimal inhibitory concentration determined using Etest strips. Mean value (range in parenthesis).
§p<0.001 by χ2 test.
¶p<0.001 by t-test. 
**p<0.001 by t-test. Presence of TetRA(33) appears to induce a small, statistically significant MIC increase, but MIC remains below the Clinical and Laboratory Standards Institute susceptibility breakpoint for doxycycline (susceptible <4 μg/mL, intermediate 8 μg/mL, resistant >16 μg/mL).

Main Article

References
  1. Prescott  JF. Rhodococcus equi: an animal and human pathogen. Clin Microbiol Rev. 1991;4:20–34. DOIPubMedGoogle Scholar
  2. Vázquez-Boland  JA, Giguère  S, Hapeshi  A, MacArthur  I, Anastasi  E, Valero-Rello  A. Rhodococcus equi: the many facets of a pathogenic actinomycete. Vet Microbiol. 2013;167:9–33. DOIPubMedGoogle Scholar
  3. Yamshchikov  AV, Schuetz  A, Lyon  GM. Rhodococcus equi infection. Lancet Infect Dis. 2010;10:350–9. DOIPubMedGoogle Scholar
  4. MacArthur  I, Anastasi  E, Alvarez  S, Scortti  M, Vázquez-Boland  JA. Comparative genomics of Rhodococcus equi virulence plasmids indicates host-driven evolution of the vap pathogenicity island. Genome Biol Evol. 2017;9:1241–7. DOIPubMedGoogle Scholar
  5. Ocampo-Sosa  AA, Lewis  DA, Navas  J, Quigley  F, Callejo  R, Scortti  M, et al. Molecular epidemiology of Rhodococcus equi based on traA, vapA, and vapB virulence plasmid markers. J Infect Dis. 2007;196:763–9. DOIPubMedGoogle Scholar
  6. Vázquez-Boland  JA, Meijer  WG. The pathogenic actinobacterium Rhodococcus equi: what’s in a name? Mol Microbiol. 2019;112:1–15. DOIPubMedGoogle Scholar
  7. Muscatello  G, Leadon  DP, Klayt  M, Ocampo-Sosa  A, Lewis  DA, Fogarty  U, et al. Rhodococcus equi infection in foals: the science of ‘rattles’. Equine Vet J. 2007;39:470–8. DOIPubMedGoogle Scholar
  8. Giguère  S. Treatment of infections caused by Rhodococcus equi. Vet Clin North Am Equine Pract. 2017;33:67–85. DOIPubMedGoogle Scholar
  9. Giguère  S, Cohen  ND, Chaffin  MK, Slovis  NM, Hondalus  MK, Hines  SA, et al. Diagnosis, treatment, control, and prevention of infections caused by Rhodococcus equi in foals. J Vet Intern Med. 2011;25:1209–20. DOIPubMedGoogle Scholar
  10. Burton  AJ, Giguère  S, Sturgill  TL, Berghaus  LJ, Slovis  NM, Whitman  JL, et al. Macrolide- and rifampin-resistant Rhodococcus equi on a horse breeding farm, Kentucky, USA. Emerg Infect Dis. 2013;19:282–5. DOIPubMedGoogle Scholar
  11. Giguère  S, Lee  E, Williams  E, Cohen  ND, Chaffin  MK, Halbert  N, et al. Determination of the prevalence of antimicrobial resistance to macrolide antimicrobials or rifampin in Rhodococcus equi isolates and treatment outcome in foals infected with antimicrobial-resistant isolates of R equi. J Am Vet Med Assoc. 2010;237:74–81. DOIPubMedGoogle Scholar
  12. Huber  L, Giguère  S, Slovis  NM, Carter  CN, Barr  BS, Cohen  ND, et al. Emergence of resistance to macrolides and rifampin in clinical isolates of Rhodococcus equi from foals in central Kentucky, 1995 to 2017. Antimicrob Agents Chemother. 2018;63:e01714–8. DOIPubMedGoogle Scholar
  13. Anastasi  E, Giguère  S, Berghaus  LJ, Hondalus  MK, Willingham-Lane  JM, MacArthur  I, et al. Novel transferable erm(46) determinant responsible for emerging macrolide resistance in Rhodococcus equi. J Antimicrob Chemother. 2015;70:3184–90.PubMedGoogle Scholar
  14. Erol  E, Locke  S, Saied  A, Cruz Penn  MJ, Smith  J, Fortner  J, et al. Antimicrobial susceptibility patterns of Rhodococcus equi from necropsied foals with rhodococcosis. Vet Microbiol. 2020;242:108568. DOIPubMedGoogle Scholar
  15. Álvarez-Narváez  S, Giguère  S, Anastasi  E, Hearn  J, Scortti  M, Vázquez-Boland  JA. Clonal confinement of a highly mobile resistance element driven by combination therapy in Rhodococcus equi. MBio. 2019;10:e02260–19. DOIPubMedGoogle Scholar
  16. Berghaus  LJ, Giguère  S, Guldbech  K, Warner  E, Ugorji  U, Berghaus  RD. Comparison of Etest, disk diffusion, and broth macrodilution for in vitro susceptibility testing of Rhodococcus equi. J Clin Microbiol. 2015;53:314–8. DOIPubMedGoogle Scholar
  17. Koren  S, Walenz  BP, Berlin  K, Miller  JR, Bergman  NH, Phillippy  AM. Canu: scalable and accurate long-read assembly via adaptive k-mer weighting and repeat separation. Genome Res. 2017;27:722–36. DOIPubMedGoogle Scholar
  18. Treangen  TJ, Ondov  BD, Koren  S, Phillippy  AM. The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes. Genome Biol. 2014;15:524. DOIPubMedGoogle Scholar
  19. Price  MN, Dehal  PS, Arkin  AP. FastTree 2—approximately maximum-likelihood trees for large alignments. PLoS One. 2010;5:e9490. DOIPubMedGoogle Scholar
  20. Anastasi  E, MacArthur  I, Scortti  M, Alvarez  S, Giguère  S, Vázquez-Boland  JA. Pangenome and phylogenomic analysis of the pathogenic actinobacterium Rhodococcus equi. Genome Biol Evol. 2016;8:3140–8. DOIPubMedGoogle Scholar
  21. Cohen  ND, Smith  KE, Ficht  TA, Takai  S, Libal  MC, West  BR, et al. Epidemiologic study of results of pulsed-field gel electrophoresis of isolates of Rhodococcus equi obtained from horses and horse farms. Am J Vet Res. 2003;64:153–61. DOIPubMedGoogle Scholar
  22. Morton  AC, Begg  AP, Anderson  GA, Takai  S, Lämmler  C, Browning  GF. Epidemiology of Rhodococcus equi strains on Thoroughbred horse farms. Appl Environ Microbiol. 2001;67:2167–75. DOIPubMedGoogle Scholar
  23. Tauch  A, Götker  S, Pühler  A, Kalinowski  J, Thierbach  G. The 27.8-kb R-plasmid pTET3 from Corynebacterium glutamicum encodes the aminoglycoside adenyltransferase gene cassette aadA9 and the regulated tetracycline efflux system Tet 33 flanked by active copies of the widespread insertion sequence IS6100. Plasmid. 2002;48:117–29. DOIPubMedGoogle Scholar
  24. Chopra  I, Roberts  M. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev. 2001;65:232–60. DOIPubMedGoogle Scholar
  25. Targant  H, Doublet  B, Aarestrup  FM, Cloeckaert  A, Madec  JY. IS6100-mediated genetic rearrangement within the complex class 1 integron In104 of the Salmonella genomic island 1. J Antimicrob Chemother. 2010;65:1543–5. DOIPubMedGoogle Scholar
  26. Partridge  SR, Recchia  GD, Stokes  HW, Hall  RM. Family of class 1 integrons related to In4 from Tn1696. Antimicrob Agents Chemother. 2001;45:3014–20. DOIPubMedGoogle Scholar
  27. Huber  L, Giguère  S, Cohen  ND, Slovis  NM, Hanafi  A, Schuckert  A, et al. Prevalence and risk factors associated with emergence of Rhodococcus equi resistance to macrolides and rifampicin in horse-breeding farms in Kentucky, USA. Vet Microbiol. 2019;235:243–7. DOIPubMedGoogle Scholar
  28. Álvarez-Narváez  S, Berghaus  LJ, Morris  ERA, Willingham-Lane  JM, Slovis  NM, Giguere  S, et al. A common practice of widespread antimicrobial use in horse production promotes multi-drug resistance. Sci Rep. 2020;10:911. DOIPubMedGoogle Scholar
  29. Kilby  ER. The demographics of the US equine population. In: Salem DJ, Rowan AN, editors. The state of the animals. Washington (DC): Human Society Press; 2007. p. 175–205.
  30. Womble  A, Giguère  S, Lee  EA. Pharmacokinetics of oral doxycycline and concentrations in body fluids and bronchoalveolar cells of foals. J Vet Pharmacol Ther. 2007;30:187–93. DOIPubMedGoogle Scholar
  31. Collignon  PJ, Conly  JM, Andremont  A, McEwen  SA, Aidara-Kane  A, Agerso  Y, et al.; World Health Organization Advisory Group, Bogotá Meeting on Integrated Surveillance of Antimicrobial Resistance (WHO-AGISAR). World Health Organization ranking of antimicrobials according to their importance in human medicine: a critical step for developing risk management strategies to control antimicrobial resistance from food animal production. Clin Infect Dis. 2016;63:1087–93. DOIPubMedGoogle Scholar
  32. Álvarez-Narváez  S, Giguère  S, Berghaus  LJ, Dailey  C, Vázquez-Boland  JA. Horizontal spread of Rhodococcus equi macrolide resistance plasmid pRErm46 across environmental Actinobacteria. Appl Environ Microbiol. 2020;86:e00108–20. DOIPubMedGoogle Scholar
  33. Letek  M, González  P, Macarthur  I, Rodríguez  H, Freeman  TC, Valero-Rello  A, et al. The genome of a pathogenic rhodococcus: cooptive virulence underpinned by key gene acquisitions. PLoS Genet. 2010;6:e1001145. DOIPubMedGoogle Scholar

Main Article

1Deceased.

Page created: December 08, 2020
Page updated: January 23, 2021
Page reviewed: January 23, 2021
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external