Journal of Veterinary Science

The Korean Society of Veterinary Science (대한수의학회)
권호 표지
DOI QR코드

DOI QR Code

Treatment of pigs with enrofloxacin via different oral dosage forms - environmental contaminations and resistance development of Escherichia coli

  • Received : 2021.07.29
  • Accepted : 2021.12.13
  • Published : 2022.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Antibacterial agents play important roles in the treatment of bacterial infections. However, the development of antimicrobial resistance (AMR) and carry-over of substances into the environment are several problems arising during oral treatment of bacterial infections. We assessed AMR development in commensal Escherichia coli (E. coli) in enrofloxacin treated and untreated animals. In addition, we examined fluoroquinolone in the plasma and urine of treated and untreated animals, and in sedimentation dust and aerosol. Methods: In each trial, six pigs were treated with enrofloxacin via powder, granulate or pellet forms in two time periods (days 1-5 and 22-26). Four pigs served as untreated controls. The minimum inhibitory concentration (MIC) was determined to evaluate AMR development. Analysis of enro- and ciprofloxacin was performed with high performance liquid chromatography. Results: Non-wildtype E. coli (MIC > 0.125 ㎍/mL) was detected in the pellet treated group after the first treatment period, whereas in the other groups, non-wildtype isolates were found after the second treatment period. E. coli with MIC > 4 ㎍/mL was found in only the pellet trial. Untreated animals showed similar susceptibility shifts several days later. Bioavailability differed among the treatment forms (granulate > pellet > powder). Enro- and ciprofloxacin were detected in aerosols and sedimentation dust (granulate, powder > pellet). Conclusions: This study indicates that the kind of the oral dosage form of antibiotics affects environmental contamination and AMR development in commensal E. coli in treated and untreated pigs.

Keywords

Acknowledgement

We gratefully acknowledge the manufacturing of the pellets and the granulate by the Institute for Animal Nutrition, University of Veterinary Medicine Hannover Foundation and the Institute for Particle Technology (iPAT), TU Braunschweig. Furthermore, we thank I. Ruddat and L. Kreienbrock (Department of Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hannover Foundation) for statistical data analysis.

References

  1. Ungemach FR, Muller-Bahrdt D, Abraham G. Guidelines for prudent use of antimicrobials and their implications on antibiotic usage in veterinary medicine. Int J Med Microbiol. 2006;296 Suppl 41:33-38. https://doi.org/10.1016/j.ijmm.2006.01.059
  2. World Health Organization. Critically Important Antimicrobials for Human Medicine, 6th Revision. Geneva: World Health Organization; 2019, 1-45.
  3. Scheer M. Untersuchungen zur antibakteriellen Aktivitat von Baytril. Vet Med Nachr. 1987;2:90-99.
  4. Eliopoulos GM, Gardella A, Moellering RC Jr. In vitro activity of ciprofloxacin, a new carboxyquinoline antimicrobial agent. Antimicrob Agents Chemother. 1984;25(3):331-335. https://doi.org/10.1128/AAC.25.3.331
  5. Wingender W, Graefe KH, Gau W, Forster D, Beermann D, Schacht P. Pharmacokinetics of ciprofloxacin after oral and intravenous administration in healthy volunteers. Eur J Clin Microbiol. 1984;3(4):355-359. https://doi.org/10.1007/BF01977494
  6. Tyczkowska K, Hedeen KM, Aucoin DP, Aronson AL. High-performance liquid chromatographic method for the simultaneous determination of enrofloxacin and its primary metabolite ciprofloxacin in canine serum and prostatic tissue. J Chromatogr A. 1989;493(2):337-346. https://doi.org/10.1016/S0378-4347(00)82739-5
  7. Flammer K, Aucoin DP, Whitt DA. Intramuscular and oral disposition of enrofloxacin in African grey parrots following single and multiple doses. J Vet Pharmacol Ther. 1991;14(4):359-366. https://doi.org/10.1111/j.1365-2885.1991.tb00849.x
  8. Lomaestro BM, Bailie GR. Absorption interactions with fluoroquinolones. 1995 update. Drug Saf. 1995;12(5):314-333. https://doi.org/10.2165/00002018-199512050-00004
  9. Vetidata. Drug: Enrofloxacin [Internet]. Leipzig: Vetidata; https://vetidata.de/. Updated 2019. Accessed 2019 May.
  10. Burow E, Kasbohrer A. Risk factors for antimicrobial resistance in escherichia coli in pigs receiving oral antimicrobial treatment: a systematic review. Microb Drug Resist. 2017;23(2):194-205. https://doi.org/10.1089/mdr.2015.0318
  11. Hamscher G, Pawelzick HT, Sczesny S, Nau H, Hartung J. Antibiotics in dust originating from a pig-fattening farm: a new source of health hazard for farmers? Environ Health Perspect. 2003;111(13):1590-1594. https://doi.org/10.1289/ehp.6288
  12. Wiuff C, Lykkesfeldt J, Svendsen O, Aarestrup FM. The effects of oral and intramuscular administration and dose escalation of enrofloxacin on the selection of quinolone resistance among Salmonella and coliforms in pigs. Res Vet Sci. 2003;75(3):185-193. https://doi.org/10.1016/S0034-5288(03)00112-7
  13. Kietzmann M, Markus W, Chavez J, Bollwahn W. Drug residues in untreated swine. Dtsch Tierarztl Wochenschr. 1995;102(11):441-442.
  14. Stahl J, Zessel K, Schulz J, Finke JH, Muller-Goymann CC, Kietzmann M. The effect of miscellaneous oral dosage forms on the environmental pollution of sulfonamides in pig holdings. BMC Vet Res. 2016;12(1):68. https://doi.org/10.1186/s12917-016-0688-6
  15. Merle R, Hajek P, Kasbohrer A, Hegger-Gravenhorst C, Mollenhauer Y, Robanus M, et al. Monitoring of antibiotic consumption in livestock: a German feasibility study. Prev Vet Med. 2012;104(1-2):34-43. https://doi.org/10.1016/j.prevetmed.2011.10.013
  16. Kietzmann M, Baumer W. Oral medication via feed and water -- pharmacological aspects. Dtsch Tierarztl Wochenschr. 2009;116(6):204-208.
  17. Romer A, Scherz G, Reupke S, Meissner J, Wallmann J, Kietzmann M, et al. Effects of intramuscularly administered enrofloxacin on the susceptibility of commensal intestinal Escherichia coli in pigs (sus scrofa domestica). BMC Vet Res. 2017;13(1):378. https://doi.org/10.1186/s12917-017-1260-8
  18. Scherz G, Stahl J, Glunder G, Kietzmann M. Effects of carry-over of fluoroquinolones on the susceptibility of commensal Escherichia coli in the intestinal microbiota of poultry. Berl Munch Tierarztl Wochenschr. 2014;127(11-12):478-485.
  19. EUCAST. Antimicrobial wild type distributions of microorganisms. https://mic.eucast.org/Eucast2/regShow.jsp?Id=9596. Updated 2017. Accessed June 2021.
  20. Baptista B, Delgado M, Costa M, Mendonc N, Duarte Correia JH, Canic M, et al. In vitro activity of enrofloxacin, marbofloxacin, orbifloxacin and ciprofloxacin against clinical Escherichia coli strains isolated from food-producing animals in Portugal. J Vet Pharmacol Ther. 2009;29:76.
  21. Bagel S, Hullen V, Wiedemann B, Heisig P. Impact of gyrA and parC mutations on quinolone resistance, doubling time, and supercoiling degree of Escherichia coli. Antimicrob Agents Chemother. 1999;43(4):868-875. https://doi.org/10.1128/AAC.43.4.868
  22. Chang SK, Wei HW, Lo DY, Kuo HC. Antimicrobial resistance of Escherichia coli isolates from canine urinary tract infections. J Vet Med Sci. 2015;77(1):59-65. https://doi.org/10.1292/jvms.13-0281
  23. Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. P T. 2015;40(4):277-283.
  24. Lutz EA, McCarty MJ, Mollenkopf DF, Funk JA, Gebreyes WA, Wittum TE. Ceftiofur use in finishing swine barns and the recovery of fecal Escherichia coli or Salmonella spp. resistant to ceftriaxone. Foodborne Pathog Dis. 2011;8(11):1229-1234. https://doi.org/10.1089/fpd.2011.0925
  25. Chantziaras I, Smet A, Haesebrouck F, Boyen F, Dewulf J. Studying the effect of administration route and treatment dose on the selection of enrofloxacin resistance in commensal Escherichia coli in broilers. J Antimicrob Chemother. 2017;72(7):2142. https://doi.org/10.1093/jac/dkx162
  26. Wagner BA, Straw BE, Fedorka-Cray PJ, Dargatz DA. Effect of antimicrobial dosage regimen on Salmonella and Escherichia coli isolates from feeder swine. Appl Environ Microbiol. 2008;74(6):1731-1739. https://doi.org/10.1128/AEM.01132-07
  27. Mazurek J, Pusz P, Bok E, Stosik M, Baldy-Chudzik K. The phenotypic and genotypic characteristics of antibiotic resistance in Escherichia coli populations isolated from farm animals with different exposure to antimicrobial agents. Pol J Microbiol. 2013;62(2):173-179. https://doi.org/10.33073/pjm-2013-022
  28. Aarestrup FM. Association between the consumption of antimicrobial agents in animal husbandry and the occurrence of resistant bacteria among food animals. Int J Antimicrob Agents. 1999;12(4):279-285. https://doi.org/10.1016/S0924-8579(99)90059-6
  29. Witte W, Klare I. Antibiotikaresistenz Bei Bakteriellen Infektionserregern. Berlin: Springer Verlag; 1999.
  30. Schwarz S, Kehrenberg C, Walsh TR. Use of antimicrobial agents in veterinary medicine and food animal production. Int J Antimicrob Agents. 2001;17(6):431-437. https://doi.org/10.1016/S0924-8579(01)00297-7
  31. Looft T, Johnson TA, Allen HK, Bayles DO, Alt DP, Stedtfeld RD, et al. In-feed antibiotic effects on the swine intestinal microbiome. Proc Natl Acad Sci U S A. 2012;109(5):1691-1696. https://doi.org/10.1073/pnas.1120238109
  32. Beyer A, Baumann S, Scherz G, Stahl J, von Bergen M, Friese A, et al. Effects of ceftiofur treatment on the susceptibility of commensal porcine E.coli--comparison between treated and untreated animals housed in the same stable. BMC Vet Res. 2015;11(1):265. https://doi.org/10.1186/s12917-015-0578-3
  33. Schulz J, Kemper N, Hartung J, Janusch F, Mohring SA, Hamscher G. Analysis of fluoroquinolones in dusts from intensive livestock farming and the co-occurrence of fluoroquinolone-resistant Escherichia coli. Sci Rep. 2019;9(1):5117. https://doi.org/10.1038/s41598-019-41528-z
  34. Schulz J, Ruddat I, Hartung J, Hamscher G, Kemper N, Ewers C. Antimicrobial-resistant Escherichia coli survived in dust samples for more than 20 years. Front Microbiol. 2016;7:866. https://doi.org/10.3389/fmicb.2016.00866
  35. Shallcross LJ, Davies SC. The World Health Assembly resolution on antimicrobial resistance. J Antimicrob Chemother. 2014;69(11):2883-2885. https://doi.org/10.1093/jac/dku346
  36. Studzinski T. The post-natal changes in minimal metabolic rate in the pig. J Physiol. 1972;224(2):305-316. https://doi.org/10.1113/jphysiol.1972.sp009896
  37. Donham KJ, Zavala DC, Merchant J. Acute effects of the work environment on pulmonary functions of swine confinement workers. Am J Ind Med. 1984;5(5):367-375. https://doi.org/10.1002/ajim.4700050505
  38. Zhou J, Dong Y, Zhao X, Lee S, Amin A, Ramaswamy S, et al. Selection of antibiotic-resistant bacterial mutants: allelic diversity among fluoroquinolone-resistant mutations. J Infect Dis. 2000;182(2):517-525. https://doi.org/10.1086/315708
  39. Drlica K. The mutant selection window and antimicrobial resistance. J Antimicrob Chemother. 2003;52(1):11-17. https://doi.org/10.1093/jac/dkg269