Canine blastomycosis: A review and update on diagnosis and treatment - Veterinary Medicine
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Canine blastomycosis: A review and update on diagnosis and treatment
This fungal disease, which readily infects dogs and people, typically starts out in the lungs but can go on to invade many tissues throughout the body. Identifying it quickly and implementing antifungal therapy can result in a good prognosis.


VETERINARY MEDICINE


Azole antifungals

The azole antifungals ketoconazole, itraconazole, fluconazole, and voriconazole interfere with ergosterol synthesis. Ketoconazole is less expensive than the other azole antifungals, but treating canine blastomycosis with ketoconazole alone results in disease resolution in < 50% of cases and is associated with a high rate of relapse and adverse effects.2,17,37

Itraconazole. Itraconazole is the azole most often recommended for treating dogs with blastomycosis since it is as effective as amphotericin B but is associated with fewer adverse effects and can be administered orally.1,4,17,34,37 Itraconazole is a weak base that is best absorbed when administered with food. Peak plasma concentrations do not occur until six to 14 days after treatment is begun, resulting in some lag time before clinical response. Itraconazole is extensively bound to plasma proteins and is lipophilic, leading to good distribution throughout most tissues, but concentrations in urine and CSF are low. Itraconazole does not cross the normal blood-brain, blood-prostate, or blood-ocular barrier, but infections with Blastomyces organisms at these sites often respond well to treatment with itraconazole, perhaps because of increased penetration of the drug when inflammation is present.34,36 Itraconazole is typically administered at a dose of 5 mg/kg orally twice a day for five days, followed by 5 mg/kg once daily, or divided twice daily, for the remainder of the treatment period.1,2,17,34

Most dogs receiving 5 mg/kg/day of itraconazole do not develop any clinical signs of toxicosis. Asymptomatic increases in alanine transaminase (ALT) activity are common but should not prompt a change in therapy unless the dog exhibits anorexia, vomiting, or abdominal pain.1,34 Most gastrointestinal side effects are dose-related and will resolve if the drug is discontinued until the dog's appetite returns and then reinstituted at half the former dose.1,34

Vasculitis resulting in ulcerative dermatitis or limb swelling develops in 7.5% of dogs receiving a high dose of itraconazole (10 mg/kg/day) but does not develop in dogs receiving 5 mg/kg/day. Be sure to distinguish this drug reaction from a manifestation of cutaneous blastomycosis. Reducing the daily-administered dose of itraconazole to 5 mg/kg usually results in rapid healing of the ulcerated lesions and resolution of limb edema.17

Fluconazole. Fluconazole is an azole antifungal that is minimally protein bound and highly water soluble, penetrating the blood-brain, blood-prostate, and blood-ocular barriers well and achieving high concentrations in urine, CSF, and ocular fluids.4,23,24 Fluconazole (2.5 to 5 mg/kg orally or intravenously twice a day) may have a role in treating CNS, prostatic, and urinary blastomycosis, but itraconazole is more effective in most dogs with blastomycosis.4,37

Voriconazole. Voriconazole is a derivative of fluconazole that has a broader spectrum of action, improving its efficacy against blastomycosis while maintaining wide tissue distribution and the ability to cross the blood-brain, blood-ocular, and blood-prostate barriers. As such, this drug may be effective in treating CNS fungal infections including blastomycosis. The dose in dogs has not been well-established, but 5 to 10 mg/kg orally or intravenously twice a day has been recommended.

DURATION OF THERAPY AND RESPONSE TO TREATMENT

About 70% to 80% of dogs with blastomycosis respond completely to treatment with itraconazole, amphotericin B, or the two drugs in combination.1,2,17,37 When the drugs are used in combination, they are administered simultaneously initially, and then the itraconazole is continued as a sole agent once the desired cumulative dose of amphotericin B has been administered.

Administer itraconazole or the other azoles for at least 60 days in all infected dogs, and continue for at least one month after all clinical and radiographic evidence of disease has resolved.12,17 Treat dogs with severe lung involvement for at least 90 days. Even with appropriate duration of treatment, 20% to 25% of dogs will relapse after itraconazole therapy. The likelihood of relapse is related to the severity of the initial lung disease, and it most often occurs within six months of therapy cessation.1 Retreatment with an additional 60- to 90-day course of itraconazole has an 80% chance of producing a cure.1

PROGNOSIS

The two most important negative prognostic factors are CNS involvement and severe lung disease.1,4,17 Most dogs with brain involvement will die, but aggressive treatment with amphotericin B, fluconazole, or voriconazole may occasionally be effective.1

Dogs with severe diffuse pulmonary blastomycosis often deteriorate during the first two or three days of treatment, perhaps related to an inflammatory response directed against dying organisms in the lungs.1,2,17 Fifty percent of these dogs will die within the first seven days of therapy.1 Anti-inflammatory dosages of dexamethasone (0.25 mg/kg intravenously once a day for two or three days) should be routinely administered to dogs with severe pulmonary infiltrates that develop worsening respiratory distress during antifungal therapy.1 Dogs that receive glucocorticoids and recover should then be treated for at least 90 days with antifungal drugs.

Although itraconazole does not normally achieve high concentrations in the eye, the response to treatment with a high itraconazole dose (5 mg/kg b.i.d.) in dogs with mild posterior segment disease without complete retinal separation has been good, with most dogs being cured and retaining vision in the affected eyes.13,38,39 Blind eyes that are severely affected with glaucoma or endophthalmitis are unlikely to become visual and should probably be enucleated to prevent them from serving as a persistent focus of infection.12,14,15,40

PUBLIC HEALTH CONCERNS

At 98.6 F (37 C) or above, B. dermatitidis exists in a yeast phase that is too large to be transmitted by coughing to other dogs or to people as an aerosol. Cutaneous inoculation through needle sticks or wound contamination has, however, been reported.1,4 The organism's mycelial phase may form in bandaged skin lesions4 and may aerosolize and infect people present during bandage changes. Draining tracts or ulcerative lesions should, thus, be left uncovered, and staff members should wear protective clothing including gloves, gowns, and surgical masks when in contact with patients with these lesions. Culture of B. dermatitidis should only be attempted in laboratories with proper facilities, and samples should be clearly marked to minimize risk to laboratory personnel4 since culture promotes growth of the highly infectious mycelial phase.

M. Casey Gaunt, DVM
Susan M. Taylor, DVM, DACVIM
Department of Small Animal Clinical Sciences
Western College of Veterinary Medicine
University of Saskatchewan
Saskatoon, SK S7N 5B4


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Source: VETERINARY MEDICINE,
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