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Home / Equine Research Bank / J Vet Pharmacol Ther / Pharmacokinetics and pharmacodynamics of doxycycline in a St...
Journal of veterinary pharmacology and therapeutics2021; 44(5); 766-775; doi: 10.1111/jvp.12982

Pharmacokinetics and pharmacodynamics of doxycycline in a Streptococcusequi subsp. zooepidemicus infection model in horses.

Abstract: The objectives of this study were to investigate the pharmacokinetics (PK), pharmacodynamics (PD), and the efficacy of oral administration of doxycycline (DXC) in horses with Streptococcus zooepidemicus tissue infections. Tissue chambers (TC) were implanted subcutaneously in the cervical region of 7 horses and inoculated with a single S. zooepidemicus isolate with a minimum inhibitory concentration (MIC) of 0.25 µg/ml, determined by agar dilution. Doxycycline hyclate (10 mg/kg, orally, q 12 h, for 5 days) mixed with poloxamer gel was started following inoculation. The TC fluid was sampled prior to and following inoculation for cytology analysis, quantitative culture, and DXC determination. Plasma DXC concentrations were measured over 48 h following the last dose of DXC administered. The mean plasma peak concentration (C ) of DXC was 0.32 µg/ml, and concentrations above the MIC were only reached in 3 TC samples. In plasma, mean T > MIC was 2.4 h, mean C /MIC was 1.30, and mean AUC /MIC was 11.63 h. These PK/PD indices did not reach the suggested targets for DXC treatments of infections, and the TC abscessed in all horses. This is the first study to evaluate the recommended dose of DXC in horse in an infection model.
© 2021 John Wiley & Sons Ltd.
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Publication Date: 2021-05-31 PubMed ID: 34057219DOI: 10.1111/jvp.12982Google Scholar: Lookup
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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.

This research aims to understand the effectiveness of doxycycline, a commonly used antibiotic, against Streptococcus zooepidemicus infections in horses. The study found that the treatment, despite administration according to general recommendations, did not achieve the desired drug concentration in the horses’ systems and the infection progressed in all cases.

Experiment Methodology

  • The researchers implanted tissue chambers (TC) in seven horses and inoculated them with Streptococcus zooepidemicus, a bacterium that causes infection in various animals and humans.
  • The chambers were filled with poloxamer gel mixed with Doxycycline hyclate (DXC), an antibiotic given orally to the horses every 12 hours for 5 days.
  • The team conducted tests on the fluid in the tissue chambers and measured plasma DXC concentrations for up to 48 hours after the final dose.

Results and Observations

  • The peak concentration of doxycycline (DXC) in the horses’ plasma was lower than expected. This suggests that the drug might not have reached effective levels in horses’ bloodstream.
  • The minimum inhibitory concentration (MIC) – the lowest concentration of an antibiotic that can prevent bacterial growth – was only achieved in three tissue chamber samples. Achieving this concentration is important in ensuring the effectiveness of the antibiotic treatment.
  • Despite the DXC treatment, all the horses’ tissue chambers had abscessed, indicating the presence and progression of infection.

Significance

  • This study is significant as it’s the first to examine the efficacy of the recommended dose of doxycycline in horses using an infection model.
  • The findings suggest that the current recommended treatment dose in horses may be insufficient to treat Streptococcus zooepidemicus infections effectively.
  • Further research will be required to inform new dosage guidelines for treating such infections in horses, ensuring veterinarians have the most effective resources for treating these conditions.

Cite This Article

APA
Chapuis RJJ, Smith JS, Uehlinger FD, Meachem M, Johnson R, Dowling PM. (2021). Pharmacokinetics and pharmacodynamics of doxycycline in a Streptococcusequi subsp. zooepidemicus infection model in horses. J Vet Pharmacol Ther, 44(5), 766-775. https://doi.org/10.1111/jvp.12982

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 44
Issue: 5
Pages: 766-775

Researcher Affiliations

Chapuis, Ronan J J
  • Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Smith, Joe S
  • Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee, USA.
Uehlinger, Fabienne D
  • Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Meachem, Melissa
  • Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Johnson, Ron
  • Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
Dowling, Patricia M
  • Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

MeSH Terms

  • Administration, Oral
  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Doxycycline / therapeutic use
  • Horses
  • Microbial Sensitivity Tests / veterinary
  • Streptococcus equi

Grant Funding

  • Townsend Equine Health Research Fund of the Western College of Veterinary Medicine, University of Saskatchewan, Canada

References

This article includes 54 references
  1. Arnold CE, Chaffin MK. Abdominal abscesses in adult horses: 61 cases (1993-2008). Journal of the American Veterinary Medical Association 241(12), 1659-1665.
    doi: 10.2460/javma.241.12.1659google scholar: lookup
  2. Awosile BB, Heider LC, Saab ME, McClure JT. Antimicrobial resistance in bacteria isolated from horses from the Atlantic Provinces, Canada (1994 to 2013). Canadian Veterinary Journal 59(9), 951-957.
  3. Baker A, Plummer CE, Szabo NJ, Barrie KP, Brooks DE. Doxycycline levels in preocular tear film of horses following oral administration. Veterinary Ophthalmology 11(6), 381-385.
    doi: 10.1111/j.1463-5224.2008.00662.xgoogle scholar: lookup
  4. Barza M. The effects of protein-binding on distribution of antibiotics and the problem of continuous versus intermittent infusions. Infection 4(2), S144-S148.
    doi: 10.1007/bf01674485google scholar: lookup
  5. Beadle R, Short C, Corstvet R, Pawlusiow J, Nobles D, McClure J, Clarke C. Characterization of a soft-tissue infection model in the horse and its response to intravenous cephapirin administration. Journal of Veterinary Pharmacology and Therapeutics 12(1), 73-86.
  6. Bernard WV. Leptospirosis. The Veterinary Clinics of North America. Equine Practice 9(2), 435-444.
    doi: 10.1016/s0749-0739(17)30410-8google scholar: lookup
  7. Bryant JE, Brown MP, Gronwall RR, Merritt KA. Study of intragastric administration of doxycycline: pharmacokinetics including body fluid, endometrial and minimum inhibitory concentrations. Equine Veterinary Journal 32(3), 233-238.
    doi: 10.2746/042516400776563608google scholar: lookup
  8. Chang YF, Ku YW, Chang CF, Chang CD, McDonough SP, Divers T, Pough M, Torres A. Antibiotic treatment of experimentally Borrelia burgdorferi-infected ponies. Veterinary Microbiology 107(3-4), 285-294.
    doi: 10.1016/j.vetmic.2005.02.006google scholar: lookup
  9. Clark C, Greenwood S, Boison JO, Chirino-Trejo M, Dowling PM. Bacterial isolates from equine infections in western Canada (1998-2003). Canadian Veterinary Journal 49(2), 153-160.
  10. Clarke CR. Tissue-chamber modeling systems-applications in veterinary medicine. Journal of Veterinary Pharmacology and Therapeutics 12(4), 349-368.
    doi: 10.1111/j.1365-2885.1989.tb00686.xgoogle scholar: lookup
  11. Cunha BA, Domenico P, Cunha CB. Pharmacodynamics of doxycycline. Clinical Microbiology & Infection 6(5), 270-273.
    doi: 10.1046/j.1469-0691.2000.00058-2.xgoogle scholar: lookup
  12. Cypher EE, Kendall AT, Panizzi L, Stewart AJ, Taylor SL, Bodaan CJ, Riley CB, Gordon SJG, Whitfield LK. Medical and surgical management of an intra-abdominal abscess of hepatic origin in a horse. Journal of the American Veterinary Medical Association 247(1), 98-105.
    doi: 10.2460/javma.247.1.98google scholar: lookup
  13. Davis JL, Salmon JH, Papich MG. Pharmacokinetics and tissue distribution of doxycycline after oral administration of single and multiple doses in horses. American Journal of Veterinary Research 67(2), 310-316.
    doi: 10.2460/ajvr.67.2.310google scholar: lookup
  14. Divers TJ, Gardner RB, Madigan JE, Witonsky SG, Bertone JJ, Swinebroad EL, Johnson AL. Borrelia burgdorferi Infection and Lyme Disease in North American Horses: A Consensus Statement. Journal of Veterinary Internal Medicine 32(2), 617-632.
    doi: 10.1111/jvim.15042google scholar: lookup
  15. Ducharme N, Dill S, Shin S, Schwark W, Ducharme G, Beilman W. Phenoxymethyl penicillin in the horse: an alternative to parenteral administration of penicillin. Canadian Journal of Comparative Medicine 47(4), 436.
  16. Dunkel B, Johns IC. Antimicrobial use in critically ill horses. Journal of Veterinary Emergency and Critical Care 25(1), 89-100.
    doi: 10.1111/vec.12275google scholar: lookup
  17. Ensink JM, Bosch G, van Duijkeren E. Clinical efficacy of prophylactic administration of trimethoprim/sulfadiazine in a Streptococcus equi subsp. zooepidemicus infection model in ponies. Journal of Veterinary Pharmacology and Therapeutics 28(1), 45-49.
    doi: 10.1111/j.1365-2885.2004.00624.xgoogle scholar: lookup
  18. Ensink JM, Klein WR, Barneveld A, Vulto AG, Van Miert AS. Clinical efficacy of ampicillin, pivampicillin and procaine penicillin G in a soft tissue infection model in ponies. Journal of Veterinary Pharmacology and Therapeutics 19(6), 445-453.
    doi: 10.1111/j.1365-2885.1996.tb00081.xgoogle scholar: lookup
  19. Ensink JM, Smit JA, van Duijkeren E. Clinical efficacy of trimethoprim/sulfadiazine and procaine penicillin G in a Streptococcus equi subsp. zooepidemicus infection model in ponies. Journal of Veterinary Pharmacology and Therapeutics 26(4), 247-252.
  20. Giguere S, Belanger M. Concentration of enrofloxacin in equine tissues after long-term oral administration. Journal of Veterinary Pharmacology and Therapeutics 20(5), 402-404.
    doi: 10.1046/j.1365-2885.1997.00071.xgoogle scholar: lookup
  21. Giguere S, Burton AJ, Berghaus LJ, Haspel AD. Comparative pharmacokinetics of minocycline in foals and adult horses. Journal of Veterinary Pharmacology and Therapeutics 40(4), 335-341.
    doi: 10.1111/jvp.12366google scholar: lookup
  22. Giguere S, Sweeney RW, Belanger M. Pharmacokinetics of enrofloxacin in adult horses and concentration of the drug in serum, body fluids, and endometrial tissues after repeated intragastrically administered doses. American Journal of Veterinary Research 57(7), 1025-1030.
  23. Gilmour MA, Clarke CR, Macallister CG, Dedeo JM, Caudell DL, Morton RJ, Pugh M. Ocular penetration of oral doxycycline in the horse. Vet Ophthalmol 8(5), 331-335.
    doi: 10.1111/j.1463-5224.2005.00422.xgoogle scholar: lookup
  24. James FM, Engiles JB, Beech J. Meningitis, cranial neuritis, and radiculoneuritis associated with Borrelia burgdorferi infection in a horse. Journal of the American Veterinary Medical Association 237(10), 1180-1185.
    doi: 10.2460/javma.237.10.1180google scholar: lookup
  25. Leclere M, Magdesian KG, Cole CA, Szabo NJ, Ruby RE, Rhodes DM, Edman J, Vale A, Wilson WD, Tell LA. Pharmacokinetics and preliminary safety evaluation of azithromycin in adult horses. Journal of Veterinary Pharmacology and Therapeutics 35(6), 541-549.
    doi: 10.1111/j.1365-2885.2011.01351.xgoogle scholar: lookup
  26. Maaland MG, Papich MG, Turnidge J, Guardabassi L. Pharmacodynamics of doxycycline and tetracycline against Staphylococcus pseudintermedius: proposal of canine-specific breakpoints for doxycycline. Journal of Clinical Microbiology 51(11), 3547-3554.
    doi: 10.1128/jcm.01498-13google scholar: lookup
  27. McElligott EM, Sommardahl CS, Cox SK. Pharmacokinetics of chloramphenicol base after oral administration in adult horses. Journal of the American Veterinary Medical Association 251(1), 90-94.
    doi: 10.2460/javma.251.1.90google scholar: lookup
  28. Nagata S, Yamashita S, Kurosawa M, Kuwajima M, Hobo S, Katayama Y, Anzai T. Pharmacokinetics and tissue distribution of minocycline hydrochloride in horses. American Journal of Veterinary Research 71(9), 1062-1066.
    doi: 10.2460/ajvr.71.9.1062google scholar: lookup
  29. Nielsen EI, Friberg LE. Pharmacokinetic-pharmacodynamic modeling of antibacterial drugs. Pharmacological Reviews 65(3), 1053-1090.
    doi: 10.1124/pr.111.005769google scholar: lookup
  30. Palmer JE. Potomac horse fever. The Veterinary Clinics of North America. Equine Practice 9(2), 399-410.
    doi: 10.1016/s0749-0739(17)30406-6google scholar: lookup
  31. Prats C, El korchi G, Giralt M, Cristofol C, Pena J, Zorrilla I, Saborit J, Perez B. PK and PK/PD of doxycycline in drinking water after therapeutic use in pigs. Journal of Veterinary Pharmacology and Therapeutics 28(6), 525-530.
    doi: 10.1111/j.1365-2885.2005.00700.xgoogle scholar: lookup
  32. Prescott JF, Hoover DJ, Dohoo IR. Pharmacokinetics of erythromycin in foals and in adult horses. Journal of Veterinary Pharmacology and Therapeutics 6(1), 67-73.
    doi: 10.1111/j.1365-2885.1983.tb00456.xgoogle scholar: lookup
  33. Reuss SM, Cohen ND. Update on bacterial pneumonia in the foal and weanling. The Veterinary Clinics of North America. Equine Practice 31(1), 121-135.
    doi: 10.1016/j.cveq.2014.11.004google scholar: lookup
  34. Reuss SM, Giguere S. Update on bacterial pneumonia and pleuropneumonia in the adult horse. The Veterinary Clinics of North America. Equine Practice 31(1), 105-120.
    doi: 10.1016/j.cveq.2014.11.002google scholar: lookup
  35. Riond JL, Riviere JE, Duckett WM, Atkins CE, Jernigan AD, Rikihisa Y, Spurlock SL. Cardiovascular effects and fatalities associated with intravenous administration of doxycycline to horses and ponies. Equine Veterinary Journal 24(1), 41-45.
    doi: 10.1111/j.2042-3306.1992.tb02777.xgoogle scholar: lookup
  36. Saqib M, Muhammad G, Naureen A, Hussain MH, Asi M, Mansoor M, Toufeer M, Khan I, Neubauer H, Sprague LD. Effectiveness of an antimicrobial treatment scheme in a confined glanders outbreak. BMC Veterinary Research 8, 214.
    doi: 10.1186/1746-6148-8-214google scholar: lookup
  37. Schnabel LV, Papich MG, Divers TJ, Altier C, Aprea MS, McCarrel TM, Fortier LA. Pharmacokinetics and distribution of minocycline in mature horses after oral administration of multiple doses and comparison with minimum inhibitory concentrations. Equine Veterinary Journal 44(4), 453-458.
    doi: 10.1111/j.2042-3306.2011.00459.xgoogle scholar: lookup
  38. Schnabel LV, Papich MG, Watts AE, Fortier LA. Orally administered doxycycline accumulates in synovial fluid compared to plasma. Equine Veterinary Journal 42(3), 208-212.
    doi: 10.2746/042516409x478514google scholar: lookup
  39. Schneider RK, Bramlage LR, Mecklenburg LM, Moore RM, Gabel AA. Open drainage, intra-articular and systemic antibiotics in the treatment of septic arthritis/tenosynovitis in horses. Equine Veterinary Journal 24(6), 443-449.
    doi: 10.1111/j.2042-3306.1992.tb02874.xgoogle scholar: lookup
  40. Steinman A, Gips M, Lavy E, Sinay I, Soback S. Pharmacokinetics of metronidazole in horses after intravenous, rectal and oral administration. Journal of Veterinary Pharmacology and Therapeutics 23(6), 353-357.
    doi: 10.1046/j.1365-2885.2000.00294.xgoogle scholar: lookup
  41. Toutain PL, Lees P. Integration and modelling of pharmacokinetic and pharmacodynamic data to optimize dosage regimens in veterinary medicine. Journal of Veterinary Pharmacology and Therapeutics 27(6), 467-477.
    doi: 10.1111/j.1365-2885.2004.00613.xgoogle scholar: lookup
  42. Toutain PL, Pelligand L, Lees P, Bousquet-Mélou A, Ferran AA, Turnidge JD. The pharmacokinetic/pharmacodynamic paradigm for antimicrobial drugs in veterinary medicine: Recent advances and critical appraisal. Journal of Veterinary Pharmacology and Therapeutics 44(2), 172-200.
    doi: 10.1111/jvp.12917google scholar: lookup
  43. Wagner B, Glaser A, Bartol J, Mahar O, Johnson A, Divers T. A new sensitive Lyme multiplex assay to confirm neuroborreliosis in horses: a case report. AAEP Proceeding 57, 70-75.
  44. Wagner C, Sauermann R, Joukhadar C. Principles of antibiotic penetration into abscess fluid. Pharmacology 78(1), 1-10.
    doi: 10.1159/000094668google scholar: lookup
  45. Washburn KE, Fajt VR, Lawhon SD, Adams LG, Tell LA, Bissett WT. Caprine abscess model of tulathromycin concentrations in interstitial fluid from tissue chambers inoculated with Corynebacterium pseudotuberculosis following subcutaneous or intrachamber administration. Antimicrobial Agents and Chemotherapy 57(12), 6295-6304.
    doi: 10.1128/aac.00936-13google scholar: lookup
  46. Wayne P. Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals (3rd CLSI, supplement ed). Clinical and Laboratory Standards Institute .
  47. Wayne P. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. (I. Clinical Laboratory Standards Ed. Eleventh ed.). Clinical and Laboratory Standards Institute .
  48. Wayne P. Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals (4th CLSI, supplement ed.). Clinical and Laboratory Standards Institute .
  49. Weese JS, Giguere S, Guardabassi L, Morley PS, Papich M, Ricciuto DR, Sykes JE. ACVIM consensus statement on therapeutic antimicrobial use in animals and antimicrobial resistance. Journal of Veterinary Internal Medicine 29(2), 487-498.
    doi: 10.1111/jvim.12562google scholar: lookup
  50. Winther L, Honore Hansen S, Baptiste KE, Friis C. Antimicrobial disposition in pulmonary epithelial lining fluid of horses, part II. Doxycycline. Journal of Veterinary Pharmacology and Therapeutics 34(3), 285-289.
    doi: 10.1111/j.1365-2885.2010.01229.xgoogle scholar: lookup
  51. Womble A, Giguere S, Lee EA. Pharmacokinetics of oral doxycycline and concentrations in body fluids and bronchoalveolar cells of foals. Journal of Veterinary Pharmacology and Therapeutics 30(3), 187-193.
    doi: 10.1111/j.1365-2885.2007.00857.xgoogle scholar: lookup
  52. Zhang L, Li Y, Wang Y, Sajid A, Ahmed S, Li X. Integration of pharmacokinetic-pharmacodynamic for dose optimization of doxycycline against Haemophilus parasuis in pigs. Journal of Veterinary Pharmacology and Therapeutics 41(5), 706-718.
  53. Zhang N, Gu X, Ye X, Wu X, Zhang B, Zhang L, Shen X, Jiang H, Ding H. The PK/PD interactions of doxycycline against Mycoplasma gallisepticum. Frontiers in Microbiology 7, 653.
    doi: 10.3389/fmicb.2016.00653google scholar: lookup
  54. Zozaya H, Gutierrez L, Bernad MJ, Sumano H. Pharmacokinetics of a peroral single dose of two long-acting formulations and an aqueous formulation of doxycycline hyclate in horses. Acta Veterinaria Scandinavica 55, 21.
    doi: 10.1186/1751-0147-55-21google scholar: lookup

Citations

This article has been cited 4 times.
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  4. Scantamburlo G, Nofziger C, Paulmichl M, Vanoni S. Genetic analysis of the equine orthologues for human CYP2D6: unraveling the complexity of the CYP2D family in horses. Front Vet Sci 2023;10:1188633.
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