Overview

Cryptococcosis in cats is well described and known to occur throughout the world. The disease is due to infection with Cryptococcus neoformans and is treatable with itraconazole, fluconazole or ketoconazole. Following the concepts of therapy that have evolved for N/A(L):human cryptococcosis, the obvious choices would be fluconazole and itraconazole. The progress of the disease and response to antifungals can be serologically monitored. Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) might be sought as underlying diseases that could affect the prognosis or required duration of therapy.

Some Relevant References and Their Abstracts

 

Title: Feline systemic fungal infections
Reference: Vet Clin North Am Small Anim Pract 2000 Sep;30(5):1029-50
Author: Gionfriddo JR

Abstract: Systemic fungal diseases are important diagnostic considerations in all sick cats, particularly in cats with ocular symptoms. The most common ocular manifestation of these diseases is posterior uveitis (choroiditis); however, anterior uveitis is sometimes present and is usually secondary to the inflammation in the posterior segment. Occasionally, adnexal diseases such as blepharitis, inflammation of the nictitating membrane, and ocular discharge may be present in cats with systemic mycoses. The prognosis for cats with systemic fungal diseases has changed with the advent of the triazole antifungal drugs. In the past, the prognosis was guarded to poor for survival of the cat. Today, with prolonged antifungal therapy, many cats recover completely from their disease. The prognosis for return of vision for eyes affected with systemic fungal disease is still guarded. Often, even if the infection is controlled systemically, the retina is severely damaged and may remain nonfunctional.

Title: A case of feline cryptococcosis treated with itraconazole
Reference: Mycoses 1997 Dec;40(9-10):381-3
Author: Kano R, Nakamura Y, Watari T, Tsujimoto H, Hasegawa A

Abstract: We successfully treated a feline case of cryptococcosis with itraconazole (ITZ) at a lower dosage. The patient was a 2-year-old castrated male Abyssinian cat weighing 4.1 kg and with two masses on the head. Clinical signs were sneezing and nasal discharge. The plasma cryptococcal antigen titer measured by the latex agglutination test was proved to be high (512). The biopsy specimen from the masses disclosed yeast cells which were cultured and identified to be Cryptococcus neoformans. The cat was treated with ITZ 5 mg kg-1 given orally once a day with food. After 4 weeks, treatment of ITZ discontinued, because the cat was clinically normal and the antigen titer was low (128). However, about 7 months later, a subcutaneous nodule was detected on the same area. The nasal discharge appeared again, and the cryptococcal antigen titer was 256. ITZ treatment was continued again at the same dosage for 3 months until the antigen titer was negative (< 8). Four months after discontinuation of ITZ, the cat did not relapse and the antigen titer was in the negative range. No side-effects of ITZ were detected by physical and laboratory examination.

Title: Feline cryptococcosis: a retrospective evaluation
Reference: J Am Anim Hosp Assoc 1997 Mar-Apr;33(2):118-22
Author: Gerds-Grogan S, Dayrell-Hart B

Abstract: Cryptococcus neoformans causes the most common form of feline systemic fungal disease. Nineteen cats with cryptococcosis were seen at the Veterinary Hospital of the University of Pennsylvania between April 1986 and May 1995. Compared to other studies, these 19 cases showed increased neurological and ophthalmological involvement. Males were affected more often than females. Season and environment appeared to influence time of onset or presentation to the hospital. Clinical pathology did not show typical changes. It is possible that the organism was present frequently in the urine but was mistaken for fat droplets. Treatment with ketoconazole was unrewarding in cases with central nervous system (CNS) involvement.

 

Title: Cryptococcal infection in cats: factors influencing treatment outcome, and results of sequential serum antigen titers in 35 cats
Reference: J Vet Intern Med 1997 Jan-Feb;11(1):1-4
Author: Jacobs GJ, Medleau L, Calvert C, Brown J

Abstract: The relationship between treatment outcome and location of cryptococcal infection, gender, magnitude of pretreatment cryptococcal antigen titers, results of feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) serology, and serial changes in antigen titers during and after treatment were evaluated in a prospective and nonrandomized study of 35 cats with cryptococcosis. A commercial cryptococcal latex agglutination kit (CALAS; Meridian Diagnostic Inc, Cincinnati, OH) was used to detect cryptococcal antigen in sera. All cats were treated with itraconazole (Sporanox; Janssen Pharmaceutica Inc, Titusville, NJ). Pretreatment mean log titers for serum cryptococcal antigen were not influenced by location of the infection. Treatment outcome was not influenced by gender, location of the infection, or magnitude of pretreatment serum antigen titer. Treatment outcome was influenced by FeLV and FIV status; cats seropositive for FeLV or FIV had a higher likelihood of treatment failure (P = .008). The cryptococcal antigen titers of cats successfully treated decreased with significant linearity over time during treatment (r = -.64, P < .000001), whereas the corresponding titers for cats not treated successfully did not decrease with significant linearity (r = -.03, P > .9). For cats in which treatment was successful, antigen titers decreased significantly from pretreatment values by 1.3 orders of magnitude at 2 months after initiation of treatment. By 10 months after initiating treatment, log titers decreased by at least 2 orders of magnitude in all cats successfully treated, and 9 of 16 cats had undetectable titers. In contrast, in 5 of 6 cats in which treatment failed, antigen titers were unchanged or increased in magnitude even after at least 6 months of treatment.

Title: Combination chemotherapy of canine and feline cryptococcosis using subcutaneously administered amphotericin B
Reference: Aust Vet J 1996 Apr;73(4):124-8
Author: Malik R, Craig AJ, Wigney DI, Martin P, Love DN

Abstract: Six cases (3 cats, 3 dogs) of cryptococcosis were cured using combination chemotherapy that included amphotericin B. We developed a simple, practical and inexpensive method of administering amphotericin B as a subcutaneous infusion during the treatment of these patients. For this, the calculated dose of amphotericin B (0.5 to 0.8 mg/kg) was added to 400 mL, for cats, or to 500 mL, for dogs, of 0.45% saline containing 2.5% dextrose. These amounts were given subcutaneously 2 or 3 times weekly over several months, to a total cumulative dose of 8 to 26 mg/kg body weight. Subcutaneous infusions were generally well tolerated by the animals, although concentrations of amphotericin B in excess of 20 mg/L resulted in local irritation. This protocol enabled the administration of larger, and thus more effective, quantities of amphotericin B without producing marked azotaemia.

Title: Itraconazole for the treatment of cryptococcosis in cats
Reference: J Vet Intern Med 1995 Jan-Feb;9(1):39-42
Author: Medleau L, Jacobs GJ, Marks MA

Abstract: Itraconazole was used in 35 cats with cryptococcosis. Treatment response was determined by comparing clinical signs before, during, and after treatment. It could not be evaluated in 7 cats because they died during treatment from causes unrelated to cryptococcosis. Of the remaining 28 cats, treatment response was classified as success in 16 cats (57%), as improvement in 8 cats (29%), and as a failure in 4 (14%). The failures were due to death or euthanasia from drug toxicity (1 cat), progressive fungal disease (2 cats), and relapse 1 year after treatment (1 cat). The cats that improved did not undergo a 1-year posttreatment evaluation because they were lost to follow-up (3 cats), died or were euthanatized for other reasons (4 cats), or had a noncompliant owner (1 cat). For the 16 cats in which treatment was successful, the median itraconazole dose was 13.8 mg/kg body weight daily (range, 10.9 to 26.7 mg/kg/d), and the median duration of treatment was 8.5 months (range, 4 to 16 months). Five of these cats had previously been treated unsuccessfully with ketoconazole.

Title: Cryptococcosis in cats: clinical and mycological assessment of 29 cases and evaluation of treatment using orally administered fluconazole
Reference: J Med Vet Mycol 1992;30(2):133-44
Author: Malik R, Wigney DI, Muir DB, Gregory DJ, Love DN

Abstract: Twenty-nine cats with naturally occurring cryptococcosis were evaluated prior to commencing oral fluconazole therapy (25-100 mg every 12 h). Affected cats ranged from 2 to 15 years-of-age. Male cats (19; 66%) and Siamese cats (5; 21%) appeared to be over-represented in comparison to the hospital’s cat population. Mycotic rhinitis was observed in 24 (83%) of the cases, although nasal cavity involvement was subtle in four animals. Disease of the skin and subcutaneous tissues was present in 15 cases (52%) and amongst these the nasal plane (seven cats) and bridge of the nose (seven cats) were most commonly involved. Primary infection of the central nervous system was not encountered, although one cat developed meningoencephalitis and optic neuritis as a sequel to longstanding nasal cavity disease. Antibodies against the feline immunodeficiency virus (FIV) were detected in eight cats (28%), and these cats tended to have advanced and/or disseminated disease. There was a tendency for cats to develop cryptococcosis during the Australian summer. Organisms were cultured from 27 cases. Cryptococcus neoformans var. neoformans was isolated from 21 cats, while C. neoformans var. gattii was identified in the remaining six. The response to oral fluconazole was excellent in this series, which included many cats with advanced, longstanding or disseminated disease. The fungal infection resolved in all but one advanced case which died after only 4 days of therapy. A dose of 50 mg per cat, given every 12 h, produced a consistently good response without side effects. Lower doses were effective in some cases, while 100 mg every 12 h was required to control the infection in one cat. Serum fluconazole levels obtained during chronic dosing (50 +/- 18 mg l-1, mean +/- SD; 50 mg per cat every 12 h) were highly variable (range 15-80 mg l-1). Concurrent FIV infection did not impart an unfavourable prognosis, although affected cats often required prolonged courses of therapy.

Title: Evaluation of ketoconazole and itraconazole for treatment of disseminated cryptococcosis in cats
Reference: Am J Vet Res 1990 Sep;51(9):1454-8
Author: Medleau L, Greene CE, Rakich PM

Abstract: During the first part of a study, cats were inoculated with Cryptococcus neoformans via the following routes: intradermal, intranasal, IV, and intracisternal. Only use of the IV route of inoculation consistently induced disseminated cryptococcosis. In the second part of the study, disseminated cryptococcosis was experimentally induced in cats via IV inoculation of C neoformans. One month after inoculation, 3 cats were treated with ketoconazole (10 mg/kg of body weight/d) and 3 cats were treated with itraconazole (10 mg/kg/d) for 3 months. One of the ketoconazole-treated and 2 of the itraconazole-treated cats also had cryptococcosis of the CNS when treatment was begun. During treatment, serum cryptococcal antigen titer progressively decreased in all cats. Abnormalities in CBC values or the serum biochemical profile were not found in any cat during treatment. However, all ketoconazole-treated cats became anorectic and lost weight. Side effects were not seen in itraconazole-treated cats. During the 3-month posttreatment observation period, all cats remained healthy. At necropsy, histologic evidence of cryptococcosis was not found in the 3 ketoconazole-treated cats or in 2 of the itraconazole-treated cats. In the third itraconazole-treated cat, cryptococcal organisms were found in the kidneys.

Title: Treatment of cryptococcosis in three cats, using ketoconazole
Reference: J Am Vet Med Assoc 1986 Mar 1;188(5):536-8
Author: Pentlarge VW, Martin RA

Abstract: Ketoconazole was effective in the treatment of cryptococcosis in 3 cats. A dosage of 10 to 15 mg/kg of body weight was given once or twice daily with a meal for 11 to 33 weeks. Fungal cultures and serotesting were used to assess the efficacy of treatment and resolution of active infection. In some of the cats, the treatment was associated with gastrointestinal signs and increased serum liver enzyme activity. Ketoconazole has been used in human beings, dogs, and cats for the treatment of systemic mycoses.

Title: Ketoconazole for successful treatment of cryptococcosis in a cat
Reference: J Am Vet Med Assoc 1985 Sep 1;187(5):508-9
Author: Schulman J

Abstract: Cryptococcosis affecting the skin and a lymph node in a 1 1/2-year-old cat was treated successfully with ketoconazole as the sole therapeutic agent. The cat was lesion-free 1 year after treatment.