• 1. Patterson TF, Thompson GR III, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2016;63:e1e60.

    • Search Google Scholar
    • Export Citation
  • 2. Lemetayer JD, Dowling PM, Taylor SM, et al. Pharmacokinetics and distribution of voriconazole in body fluids of dogs after repeated oral dosing. J Vet Pharmacol Ther 2015;38:451456.

    • Search Google Scholar
    • Export Citation
  • 3. Claeys S, Lefebvre JB, Schuller S, et al. Surgical treatment of canine nasal aspergillosis by rhinotomy combined with enilconazole infusion and oral itraconazole. J Small Anim Pract 2006;47:320324.

    • Search Google Scholar
    • Export Citation
  • 4. Plickert HD, Tichy A, Hirt RA. Characteristics of canine nasal discharge related to intranasal disease: a retrospective study of 105 cases. J Small Anim Pract 2014;55:145152.

    • Search Google Scholar
    • Export Citation
  • 5. Lobetti RG. A retrospective study of chronic nasal disease in 75 dogs. J S Afr Vet Assoc 2009;80:224228.

  • 6. Zonderland JL, Störk CK, Saunders JH, et al. Intranasal infusion of enilconazole for treatment of sinonasal aspergillosis in dogs. J Am Vet Med Assoc 2002;221:14211425.

    • Search Google Scholar
    • Export Citation
  • 7. Sharman MJ, Mansfield CS. Sinonasal aspergillosis in dogs: a review. J Small Anim Pract 2012;53:434444.

  • 8. Sharman M, Lenard Z, Hosgood G, et al. Clotrimazole and enilconazole distribution within the frontal sinuses and nasal cavity of nine dogs with sinonasal aspergillosis. J Small Anim Pract 2012;53:161167.

    • Search Google Scholar
    • Export Citation
  • 9. Sissener TR, Bacon NJ, Friend E, et al. Combined clotrimazole irrigation and depot therapy for canine nasal aspergillosis. J Small Anim Pract 2006;47:312315.

    • Search Google Scholar
    • Export Citation
  • 10. Hayes GM, Demetriou JL. Distribution and persistence of topical clotrimazole after sinus infusion in normal canine cadavers. J Small Anim Pract 2012;53:95100.

    • Search Google Scholar
    • Export Citation
  • 11. Burrow R, Baker M, White L, et al. Trephination of the frontal sinuses and instillation of clotrimazole cream: a computed tomographic study in canine cadavers. Vet Surg 2013;42:322328.

    • Search Google Scholar
    • Export Citation
  • 12. Schuller S, Clercx C. Long-term outcomes in dogs with sinonasal aspergillosis treated with intranasal infusions of enilconazole. J Am Anim Hosp Assoc 2007;43:3338.

    • Search Google Scholar
    • Export Citation
  • 13. Vedrine B, Fribourg-Blanc L-A. Treatment of sinonasal aspergillosis by debridement and sinonasal deposition therapy with clotrimazole under rhinoscopic guidance. J Am Anim Hosp Assoc 2018;54:103110.

    • Search Google Scholar
    • Export Citation
  • 14. Hazuchova K, Neiger R, Stengel C. Topical treatment of mycotic rhinitis-rhinosinusitis in dogs with meticulous debridement and 1% clotrimazole cream: 64 cases (2007–2014). J Am Vet Med Assoc 2017;250:309315.

    • Search Google Scholar
    • Export Citation
  • 15. Davidson AP. Aspergillosis. In: Ettinger SJ, Feldman EC, eds. Textbook of veterinary internal medicine. 7th ed. Philadelphia: WB Saunders Co, 2000;9961002.

    • Search Google Scholar
    • Export Citation
  • 16. Sharp N, Harvey C, O'Brien J. Treatment of canine nasal aspergillosis/penicillosis with fluconazole. J Small Anim Pract 1991;32:513516.

    • Search Google Scholar
    • Export Citation
  • 17. Sharp NJ, Sullivan M. Use of ketoconazole in the treatment of canine nasal aspergillosis. J Am Vet Med Assoc 1989;194:782786.

  • 18. Como JA, Dismukes WE. Oral azole drugs as systemic antifungal therapy. N Engl J Med 1994;330:263272.

  • 19. Felton T, Troke PF, Hope WW. Tissue penetration of antifungal agents. Clin Microbiol Rev 2014;27:6888.

  • 20. Foy DS, Trepanier L. Antifungal treatment of small animal veterinary patients. Vet Clin North Am Small Anim Pract 2010;40:11711188.

    • Search Google Scholar
    • Export Citation
  • 21. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the infectious disease society of America. Clin Infect Dis 2008;46:327360.

    • Search Google Scholar
    • Export Citation
  • 22. Murphy M, Bernard EM, Ishimaru T, et al. Activity of voriconazole (UK-109,496) against clinical isolates of Aspergillus species and its effectiveness in an experimental model of invasive pulmonary aspergillosis. Antimicrob Agents Chemother 1997;41:696698.

    • Search Google Scholar
    • Export Citation
  • 23. Okabayashi K, Imaji M, Osumi T, et al. Antifungal activity of itraconazole and voriconazole against clinical isolates obtained from animals with mycoses. Nihon Ishinkin Gakkai Zasshi 2009;50:9194.

    • Search Google Scholar
    • Export Citation
  • 24. Pieper S, Kolve H, Meine T, et al. Safety and outcome of treatment with voriconazole in a large cohort of immunocompromised children and adolescents. GMS Infect Dis 2015;3:Doc01.

    • Search Google Scholar
    • Export Citation
  • 25. Corrigan VK, Legendre AM, Wheat LJ, et al. Treatment of disseminated aspergillosis with posaconazole in 10 dogs. J Vet Intern Med 2016;30:167173.

    • Search Google Scholar
    • Export Citation
  • 26. Stewart J, Bianco D. Treatment of refractory sino-nasal aspergillosis with posaconazole and terbinafine in 10 dogs. J Small Anim Pract 2017;58:504509.

    • Search Google Scholar
    • Export Citation
  • 27. Roffey SJ, Cole S, Comby P, et al. The disposition of voriconazole in mouse, rat, rabbit, guinea pig, dog, and human. Drug Metab Dispos 2003;31:731741.

    • Search Google Scholar
    • Export Citation
  • 28. Purkins L, Wood N, Ghahramani P, et al. Pharmacokinetics and safety of voriconazole following intravenous- to oral-dose escalation regimens. Antimicrob Agents Chemother 2002;46:25462553.

    • Search Google Scholar
    • Export Citation
  • 29. Dolton MJ, Ray JE, Chen SC, et al. Multicenter study of voriconazole pharmacokinetics and therapeutic drug monitoring. Antimicrob Agents Chemother 2012;56:47934799.

    • Search Google Scholar
    • Export Citation
  • 30. Sykes JE. Aspergillosis. In: Sykes JE, ed. Canine and feline infectious diseases. 2nd ed. St Louis: Elsevier Saunders Co, 2014;633648.

    • Search Google Scholar
    • Export Citation
  • 31. De Lorenzi D, Bonfanti U, Masserdotti C, et al. Diagnosis of canine nasal aspergillosis by cytological examination: a comparison of four different collection techniques. J Small Anim Pract 2006;47:316319.

    • Search Google Scholar
    • Export Citation
  • 32. Pomrantz JS, Johnson LR. Repeated rhinoscopic and serologic assessment of the effectiveness of intranasally administered clotrimazole for the treatment of nasal aspergillosis in dogs. J Am Vet Med Assoc 2010;236:757762.

    • Search Google Scholar
    • Export Citation
  • 33. Peeters D, Day MJ, Clercx C. An immunohistochemical study of canine nasal aspergillosis. J Comp Pathol 2005;132:283288.

  • 34. Belda B, Petrovitch N, Mathews KG. Sinonasal aspergillosis: outcome after topical treatment in dogs with cribriform plate lysis. J Vet Intern Med 2018;32:13531358.

    • Search Google Scholar
    • Export Citation
  • 35. Stanton JA, Miller ML, Johnson P, et al. Treatment of canine sinonasal aspergillosis with clotrimazole infusion in patients with cribriform plate lysis. J Small Anim Pract 2018;59:411414.

    • Search Google Scholar
    • Export Citation

Oral administration of voriconazole with surgical fungal plaque debridement for the treatment of sinonasal aspergillosis with cribriform plate lysis in three dogs

View More View Less
  • 1 1BluePearl Pet Hospital, 455 Abernathy Rd NE, Sandy Springs, GA 30328
  • | 2 2Care Center, 6995 E Kemper Rd, Cincinnati, OH 45249
  • | 3 3Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706
  • | 4 4BluePearl Pet Hospital, 29080 Inkster Rd, Southfeld, MI 48034

Abstract

CASE DESCRIPTION

3 dogs with chronic sinonasal signs (sneezing, nasal discharge, or epistaxis [or a combination of signs]) were examined.

CLINICAL FINDINGS

For all 3 dogs, CT revealed variable degrees of nasal turbinate destruction and frontal sinus involvement with cribriform plate lysis. Fungal plaques were detected during rhinoscopy or sinusoscopy. Results of fungal culture (2 dogs) or cytologic examination of a plaque specimen (1 dog) supported a diagnosis of sinonasal aspergillosis.

TREATMENT AND OUTCOME

All dogs underwent surgical rhinotomy or sinusotomy (or both) for fungal plaque debridement followed by oral treatment with voriconazole and periodic physical examinations, clinicopathologic analyses, and assessments of serum drug concentrations for a period ≥ 22 weeks. All dogs had considerable to complete reduction of their clinical signs and tolerated voriconazole treatment with minimal adverse effects. Adverse effects included development of reversible neurotoxicosis (associated with high serum voriconazole concentration) and mildly high serum liver enzyme activities. The dosage of voriconazole administered to achieve therapeutic serum concentrations (2.5 to 3.3 mg/kg [1.1 to 1.5 mg/lb], PO, q 12 h) was substantially lower than dosages suggested by previously published studies in dogs. The 3 dogs remained clinically normal or had mild clinical signs after voriconazole discontinuation for follow-up times of 6 to 15 months.

CLINICAL RELEVANCE

Findings in these 3 dogs indicated that surgical fungal plaque debridement followed by oral treatment with voriconazole may be an effective treatment option for dogs with sinonasal aspergillosis and cribriform plate lysis. Further evaluation of this treatment regimen with repeated CT examinations and longer follow-up times is warranted.

Abstract

CASE DESCRIPTION

3 dogs with chronic sinonasal signs (sneezing, nasal discharge, or epistaxis [or a combination of signs]) were examined.

CLINICAL FINDINGS

For all 3 dogs, CT revealed variable degrees of nasal turbinate destruction and frontal sinus involvement with cribriform plate lysis. Fungal plaques were detected during rhinoscopy or sinusoscopy. Results of fungal culture (2 dogs) or cytologic examination of a plaque specimen (1 dog) supported a diagnosis of sinonasal aspergillosis.

TREATMENT AND OUTCOME

All dogs underwent surgical rhinotomy or sinusotomy (or both) for fungal plaque debridement followed by oral treatment with voriconazole and periodic physical examinations, clinicopathologic analyses, and assessments of serum drug concentrations for a period ≥ 22 weeks. All dogs had considerable to complete reduction of their clinical signs and tolerated voriconazole treatment with minimal adverse effects. Adverse effects included development of reversible neurotoxicosis (associated with high serum voriconazole concentration) and mildly high serum liver enzyme activities. The dosage of voriconazole administered to achieve therapeutic serum concentrations (2.5 to 3.3 mg/kg [1.1 to 1.5 mg/lb], PO, q 12 h) was substantially lower than dosages suggested by previously published studies in dogs. The 3 dogs remained clinically normal or had mild clinical signs after voriconazole discontinuation for follow-up times of 6 to 15 months.

CLINICAL RELEVANCE

Findings in these 3 dogs indicated that surgical fungal plaque debridement followed by oral treatment with voriconazole may be an effective treatment option for dogs with sinonasal aspergillosis and cribriform plate lysis. Further evaluation of this treatment regimen with repeated CT examinations and longer follow-up times is warranted.

Contributor Notes

Address correspondence to Dr. Pritchard (jpritchard2@wisc.edu).