TREATMENT
Table 2. Common Antifungal Treatments for Histoplasmosis in Dogs and Cats
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Although canine pulmonary histoplasmosis may be self-limiting and resolve without treatment,7 antifungal therapy is recommended because of the risk of dissemination (Table 2).10,36 In people, itraconazole is the first-line treatment for mild to moderate pulmonary or disseminated histoplasmosis, and amphotericin
B is the first-line treatment for severe pulmonary or disseminated histoplasmosis.67 Itraconazole or amphotericin B is considered the first-line treatment for histoplasmosis in dogs and cats.10
Itraconazole
Even though itraconazole is reportedly the treatment of choice for histoplasmosis in dogs and cats,10,38 few reports of specific studies of its efficacy in these species exist. One report indicated good efficacy in eight cats
treated with itraconazole (5 mg/kg orally b.i.d.) for 60 to 130 days, with two cats relapsing and requiring additional therapy
to achieve complete remission.38 Because of marked variability in the oral absorption of itraconazole, some cats may require twice-daily dosing at 10 mg/kg.68 Different formulations of itraconazole exist (Table 2); of these, the oral suspension has the greatest bioavailability.22,68,69 Use of the intravenous formulation of itraconazole may be considered in animals that cannot be treated with an oral formulation.
However, little data exist on the use of intravenous itraconazole in dogs and cats.22,69
Fluconazole
Case example: Histoplasmosis in a Himalayan Cat
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No studies evaluating fluconazole therapy in dogs and cats with disseminated histoplasmosis exist. But since fluconazole has
increased penetration into the eye and central nervous system, it may theoretically be a better azole agent for patients that
have neurologic or ocular involvement refractory to itraconazole.10 Results of an in vitro study showed that fluconazole had a higher minimal inhibitory concentration than itraconazole for
Histoplasma species.70 However, in people, fluconazole is considered a second-line treatment for histoplasmosis,67 and in mice with experimentally induced Histoplasma species meningitis, fluconazole monotherapy was less efficacious than itraconazole or amphotericin B monotherapy.71
Ketoconazole
Successful treatment of feline histoplasmosis with varying dosages of ketoconazole has been reported.18,44,50 However, because of its reduced spectrum of activity against Histoplasma species and increased relative toxicity, ketoconazole is not a first-choice treatment.10
Voriconazole and posaconazole
Voriconazole, a triazole structurally related to fluconazole,72 and posaconazole, a triazole structurally related to itraconazole, also have activity against H. capsulatum. There are not sufficient data regarding the safety and efficacy of these newer agents in dogs and cats to warrant recommending
their use. They may be considered as rescue therapy for patients in which other treatments have failed. Pharmacokinetic data
for these agents in dogs are available.73,74
Amphotericin B
In dogs and cats with severe disseminated or pulmonary histoplasmosis, amphotericin B or combination therapy with amphotericin
B and itraconazole may provide more effective control.10 Itraconazole treatment is started at the same time as amphotericin B and is continued for the normally recommended duration
of treatment (Table 2) after amphotericin B treatment is terminated. Although typically administered intravenously, subcutaneous amphotericin
B has been used to treat cryptococcosis.75
Nephrotoxicosis is an important adverse effect of amphotericin B therapy, particularly when the deoxycholate form is used.
Since urine changes may precede serum elevations in urea nitrogen and creatinine, serial evaluation of urine specific gravity
and monitoring for evidence of casts, protein, or hematuria should be performed.22 Because of their comparatively reduced nephrotoxicity, the lipid and liposomal forms of amphotericin B are preferred, and
should be considered when amphotericin B treatment is indicated.76,77
While the lipid and liposomal forms of amphotericin B are more expensive, this increased expense must be considered in light
of increased safety. The financial and health costs of toxicosis related to using the deoxycholate form may be as much or
more of a burden than the additional cost of the lipid forms.78
Supportive therapies
Because of the risk of immunosuppression and subsequent dissemination of infection, glucocorticoids are generally not recommended
in treating histoplasmosis. However, airway obstruction from enlarged hilar lymph nodes and inflammation associated with proliferation
of the organism in the lungs can be life-threatening.10 In a study of dogs with enlarged hilar lymph nodes secondary to chronic pulmonary histoplasmosis, corticosteroid administration
(prednisone 2 mg/kg orally every 12 to 24 hours) resulted in the resolution of the clinical signs of airway obstruction in
less than one week, compared with 8.8 weeks in dogs treated with antifungal therapy.17 Only consider using corticosteroids if there is marked respiratory compromise and if no organisms are found on cytologic
or histologic evaluation. Additional supportive therapy for pulmonary histoplasmosis may include oxygen supplementation and
antibiotics, if clinically indicated.11
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