Page 1537 - Small Animal Internal Medicine, 6th Edition

CHAPTER 97 Polysystemic Mycotic Infections 1509

confirmed with molecular assays (Sykes et al., 2017). Thus
treatment responses in individual animals may be variable.
VetBooks.ir amphotericin B, ketoconazole, itraconazole, fluconazole,
Dogs and cats with cryptococcosis have been treated with
posaconazole, voriconazole, or 5-flucytosine alone and in
various combinations (see Table 97.2). Amphotericin B is
usually not indicated unless life-threatening disseminated
disease requiring rapid response to therapy is required. If
amphotericin B is deemed necessary, lipid or liposomal
encapsulated amphotericin is likely optimal because fewer
adverse effects are associated with these formulations com-
pared with regular amphotericin B. However, for owners
who cannot afford this therapy, a less expensive subcutane-
ous protocol for administration of regular amphotericin B
has been used successfully for the treatment of cryptococ-
cosis in dogs and cats and may be effective for other sys-
temic fungi susceptible to the drug (Malik et al., 1996; see
Table 97.2).
Ketoconazole, itraconazole, or fluconazole are used as a
FIG 97.5 single agent in dogs or cats without life-threatening disease.
Cytologic appearance of Cryptococcus neoformans. The
organism is 3.5 to 7.0 µm in diameter and has a thick Ketoconazole is inexpensive but commonly leads to inappe-
polysaccharide capsule. (Courtesy Dr. Dennis Macy, tence, vomiting, diarrhea, weight loss, and increases in liver
College of Veterinary Medicine and Biomedical Sciences, enzyme activities in some dogs and cats. In dogs, long-term
Colorado State University.) use of ketoconazole can suppress testosterone and cortisol
production and has been associated with cataracts. Because
of these problems, ketoconazole is used less frequently than
cases with characteristic clinical and laboratory findings but itraconazole and fluconazole. Fluconazole should be consid-
negative antigen test results. ered for dogs or cats with ocular or CNS infection. If clinical
A definitive diagnosis of cryptococcosis is based on posi- signs of toxicity develop (inappetence; drug eruptions) or
tive antigen testing, cytologic, histopathologic, culture, or increased activity of alanine aminotransferase is detected,
PCR assay demonstration of the organism (Fig. 97.5) com- drug therapy should be stopped and then reinstituted at
bined with appropriate clinical manifestations of disease. The 50% of the original dose after signs of toxicity abate. In one
organism is found during cytologic evaluation of nasal study, C. neoformans minimum inhibitory concentrations
lesions, cutaneous lesions, lymph node aspirates, CSF, and for itraconazole and voriconazole were similar (Okabayashi
bronchoalveolar lavage fluid in most affected animals; it can et al., 2009). Because voriconazole has been associated with
also be cultured. The agents can be cultured from the nasal CNS toxicity in cats, it should probably not be selected over
cavity of some asymptomatic animals, so positive culture fluconazole or itraconazole for the treatment of this disease
results do not always correlate to disease. One study evaluat- (Quimby et al., 2010).
ing subclinical carriage of C. gattii showed some animals Flucytosine crosses the blood-brain barrier better than
eliminated the infection, some remained persistently colo- ketoconazole or amphotericin B, so it has been used primar-
nized, and some progressed to clinical illness (Duncan et al., ily for the treatment of CNS cryptococcosis. It must be used
2005a). If organism numbers are low in tissues and are not in combination with other antifungal drugs and has many
detected cytologically or histopathologically, immunohisto- adverse effects, including vomiting, diarrhea, hepatotoxicity,
chemistry, PCR, and fungal culture can be used to confirm cutaneous reactions, and bone marrow suppression. One
infection (Myers et al., 2017). dog with protein-losing enteropathy from intestinal crypto-
coccosis responded to administration of terbinafine after
Treatment failing treatment with amphotericin B and fluconazole
There are molecular types of C. neoformans and C. gattii that (Olsen et al., 2012).
affect antifungal drug susceptibility (Singer et al., 2014). In Clinical signs of nasal and cutaneous cryptococcosis gen-
one study of 42 isolates, it was shown that, when compared erally resolve with treatment, but dogs or cats with CNS
with the mean inhibitory concentration (MIC) for C. neofor- or ocular disease are less likely to respond. In one study
mans, C. gattii MICs were lower for flucytosine and strain of dogs and cats with CNS cryptococcosis, 32% of the
VGIII MICs (all from cats) were lower for flucytosine and treated animals survived longer than 6 months; presence of
itraconazole. In addition, for all drugs except itraconazole, C. decreased mentation was a poor prognostic indicator (Sykes
gattii isolates exhibited a wider range of MICs than C. neofor- et al., 2010). Administration of glucocorticoids was associ-
mans. In addition, it is now known that resistance to fluco- ated with increased short-term survival in this study and one
nazole can develop in infected animals and the mechanisms other (Vorathavorn et al., 2013).