Cryptococcal Infection in Cats: Factors Influencing Treatment Outcome, and Results of Sequential Serum Antigen Titers in 35 Cats

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). Pre-treatment 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.     

Combination chemotherapy of canine and feline cryptococcosis using subcutaneously administered amphotericin B

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.     

Sequential opportunistic infections in two German Shepherd dogs

Two German Shepherd dogs with sequential opportunistic infections are described. The first was a 2-year-old male with cryptococcal rhinitis that spread to involve the optic nerves and brain. It was successfully treated with combination therapy utilising amphotericin B administered for 2 years, but the dog developed a disseminated Aspergillus deflectus infection 5 years later and was euthanased. The second case was a 4-year-old male that presented for a severe, deep-seated infection of the right antebrachium, with gradual extension to contiguous tissues. Neosartorya fischeri (anamorph; Aspergillus fischerianus) was isolated in pure culture and detected in histological sections. The infection was refractory to itraconazole, but resolved after amputation of the affected limb. Five months later, the dog developed a localised cutaneous lesion on the proximal pelvic limb, from which Pythium insidiosum was isolated and then visualised in tissue sections, together with a structure thought to be grass seed. This lesion was treated by wide surgical resection, although it was reported that the dog died of disseminated disease some months later. These cases provide further circumstantial evidence that young adult German Shepherd dogs have a predilection to developing invasive infections with fungi and other saprophytic pathogens.     

MAGNETIC RESONANCE IMAGING FEATURES AND OUTCOME FOR SOLITARY CENTRAL NERVOUS SYSTEM COCCIDIOIDES GRANULOMAS IN 11 DOGS AND CATS

Little published information is available to guide therapy for canine and feline patients with Coccidioides infections involving the central nervous system (CNS). The purpose of this cross‐sectional retrospective study was to describe magnetic resonance imaging (MRI) features and outcome for a group of dogs and cats with solitary CNS Coccidiodes granulomas. Nine canine and two feline cases met inclusion criteria; four diagnosed and treated with surgery and fluconazole and seven diagnosed by serology or cytology and treated medically. Three cases had left Coccidioides endemic areas long before developing neurological disease. The MRI lesions shared many features with neoplastic masses. The extra‐axial granulomas often had a lack of a distinct border between the mass and neural parenchyma. Four cases were extra‐axial and seven were intra‐axial, but distinguishing between extra‐axial and intra‐axial locations was sometimes challenging. The surgical cases had good outcomes and histology allowed definitive diagnosis. Medically managed patients also had generally good outcomes, with resolution of clinical signs in most cases. Findings indicated that distinction between neoplasia and focal Coccidioides granulomas based on MRI features is likely to be imprecise. Demonstration of the organism by cytology or histology is required for definitive diagnosis. The role of surgery for improving the outcome of brain or spinal coccidioidomycosis granulomas warrants further study.     

Itraconazole for the Treatment of Histoplasmosis in Cats

Eight cats with histoplasmosis were treated with itraconazole at 5 mg/kg per dose PO bid. There were multiple sites of infection, and 2 of the cats had hypercalcemia that was attributed to the histoplasmosis. All 8 cats were eventually cured, but 2 cats experienced recurrences of disease after completion of therapy, requiring 2 to 3 additional months of itraconazole. There were no clinically relevant adverse effects during treatment. Although a limited number of cats were treated, the study suggests that itraconazole is a well-tolerated and effective drug for the treatment of histoplasmosis in the cat.     

Update: Management of calcium oxalate uroliths in dogs and cats.

Calcium oxalate has become the most common mineral occurring in canine and feline uroliths. Although calcium oxalate urolith formation may be a consequence of metabolic disease, the underlying cause is not identified in many dogs and cats. Currently, there is no successful medical dissolution protocol, and calcium oxalate uroliths must be removed physically if causing problems. Effective preventative protocols are available for dogs and cats, although they are not uniformly successful.     

Treatment of refractory feline sporotrichosis with a combination of intralesional amphotericin B and oral itraconazole

OBJECTIVE To describe the use of intralesional amphotericin B in localised lesions for the treatment of 26 cats from Rio de Janeiro, Brazil, with sporotrichosis refractory to oral itraconazole. DESIGN Uncontrolled intervention study. METHOD The 26 cats in this study were diagnosed with sporotrichosis, confirmed by isolation of Sporothrix schenckii, and presented residual localised skin lesions refractory to treatment with oral itraconazole for a minimum period of 8 weeks. The animals received weekly applications of intralesional amphotericin B in conjunction with oral itraconazole. In cases of owner unavailability, a maximum of 2 weeks between the infiltrations was accepted. RESULTS Twenty-two (84.6%) of the 26 treated cats achieved clinical remission, 16 (72.7%) of which were cured, and in the remaining six (27.3%) the lesions recurred at the same site. Lack of clinical response was observed in one animal and three owners abandoned treatment. CONCLUSION The proposed therapeutic regimen is an adjunctive treatment option for cats with sporotrichosis presenting as residual skin lesions refractory to itraconazole.     

Initial and long-term efficacy of a lipid emulsion of amphotericin B desoxycholate in the management of canine leishmaniasis

Sixteen dogs in which canine leishmaniasis (CL) was diagnosed by positive identification of Leishmania amastigotes in bone marrow samples were treated with a mixture of amphotericin B (AmB) desoxycholate in soybean oil. To prevent the toxicity of AmB, dogs were pretreated with saline (50 mL/kg) and mannitol (2 g/kg). Dogs were treated twice weekly with an increasing dosage of amphotericin (0.8-2.5 mg/kg) for between 8 and 10 sessions. Transient adverse effects (anorexia, vomiting, or both) appeared in 81% of the dogs during therapy. At the end of the course, all dogs were clinically cured, with no parasites observed in bone marrow smears. Six of the 16 dogs (38%) were positive by polymerase chain reaction (PCR) in bone marrow samples at some stage of their follow-up, but only 2 were positive at the first test after treatment, which was performed within 5 months after the end of the therapy. The other 4 dogs were initially negative and became PCR-positive at subsequent examinations. Three of these 6 dogs also experienced a clinical relapse. Four dogs had at least 3 consecutive negative PCR tests during a minimum period of 18 months and were clinically cured. The results of the present study indicate that despite having a high initial effectiveness in the treatment of CL, relapses can occur with the described protocol. Also, a single negative PCR result in a recently treated dog cannot be interpreted as a complete cure.     

Use of terbinafine in the treatment protocol of intestinal Cryptococcus neoformans in a dog

A 2.5 yr old sexually intact male vizsla was admitted to the Iowa State University Veterinary Teaching Hospital for persistent diarrhea, weight loss, and panhypoproteinemia. Examination revealed an emaciated condition and melena. Two masses were palpated in the cranial abdomen. Hematology and serum biochemistry exhibited a regenerative anemia and confirmed the presence of panhypoproteinemia, suggestive of a protein-losing eneteropathy. Distinct areas of thickened intestinal wall and enlarged mesenteric lymph nodes were found on abdominal ultrasound. Cytology from those nodes showed the presence of suspected Cryptococcus spp., and infection was confirmed utilizing a cryptococcal antigen titer. Medical therapy with lipid-complexed amphotericin B and fluconazole was unsuccessful. Two surgical procedures were performed to remove the affected areas of intestine and lymph nodes, but the disease persisted as evidenced by a persistently elevated cryptococcal antigen titer. Terbinafine was prescribed, which resulted in complete resolution of clinical signs and a steadily decreasing cryptococcal antigen titer. Very few cases of intestinal cryptococcosis have been reported. In this case, infection resulted in a protein-losing enteropathy. In addition, this article describes the use of terbinafine in the treatment of intestinal cryptococcal infection in the dog, which has not been previously reported.     

Clinical signs, imaging features, neuropathology, and outcome in cats and dogs with central nervous system cryptococcosis from California

Background: Cryptococcus spp. is a fungal pathogen with a predilection for the central nervous system (CNS). Objectives: To compare the clinical, advanced imaging, and neuropathologic findings in dogs and cats with CNS cryptococcosis, and to evaluate outcome of treatment in these animals. Animals: Twenty‐six cats and 21 dogs with CNS cryptococcosis. Methods: Medical records were reviewed for clinical findings and results of CNS imaging. Archived cerebrospinal fluid and CNS tissue specimens were reviewed for pathology. Findings in cats were compared with those in dogs and the effects of variables on survival were determined by survival curve analysis. Results: When present, pain was localized to the cervical region in dogs and was generalized or localized to the thoracolumbar spine or pelvic limbs in cats. Magnetic resonance imaging (MRI) findings were variable but correlated with CNS histopathological findings of meningitis, meningitis with gelatinous pseudocyst formation, and granulomatous mass lesions. Peripherally enhancing brain lesions were seen only in cats. Histopathologically, the inflammatory response was milder in cats compared with dogs. Remissions of ≥1 year occurred in 32% of treated animals. Altered mentation was associated with negative outcome. Glucocorticoid use after diagnosis was associated with improved survival in the first 10 days. Conclusions and Clinical Importance: Lesions seen on MRI reflected neuropathological findings and were similar to those reported in human patients. The immune response to infection may differ between cats and dogs, or relate to the infecting cryptococcal species. Long‐term (>6 month median survival time) survival may be possible in animals surviving ≥4 days after diagnosis.     

Evaluation of ketoconazole and itraconazole for treatment of disseminated cryptococcosis in cats

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.     

Treatment of Blastomycosis With Itraconazole in 112 Dogs

One hundred twelve client-owned dogs with blastomycosis were treated with itraconazole, 5 or 10 mg/kg/d. The first group of 70 dogs treated in 1987 and 1988 received 10 mg/kg/d (group 1), and the second group of 42 dogs treated after October 1988 received 5 mg/kg/d (group 2). Even though the groups were treated at different times, the dogs were similar in age and gender distribution, number of sites involved, and percent and severity of pulmonary involvement. The proportion of dogs cured with a 60–day course of itraconazole was similar for both groups (53.6% versus 54.3%) and for a second historical control group treated with amphotericin B (57%); the recurrence rate was also similar, 20%, 21.4%, and 20%, respectively. Dogs treated with itraconazole had similar mortality rates (25.7% at 5 mg/kg/d; 25% at 10 mg/kg/day) to those treated with amphotericin B (23%). Seventeen of the 23 dogs that died (74%), did so during the first week of treatment; these early deaths were usually attributed to respiratory failure. The only site of infection that was significantly associated with failure (death or recurrence) was the brain. There was a marked difference in survival times between dogs without lung disease or with mild lung disease compared with dogs with moderate or severe lung disease. Serum itraconazole concentrations reached steady state by 14 days of treatment. Dogs receiving 5 mg/kg/d of itraconazole (group 2) had mean serum concentrations of 3.55 ± 2.81 mg/mL (range, 0.67 to 10.8 μg/mL), whereas dogs receiving 10 μg/kg/d (group 1) had mean concentrations of 13.46 ± 8.49 μg/mL (range, 1.8 to 28 μg/mL) (P ≤ .001). There was no association between cure and serum itraconazole concentrations. Dogs in group 1 had significantly more adverse effects than dogs in group 2 (P= .046). Anorexia was the most common adverse effect, occurring in 14.9% of dogs in group 1. Only 8% of dogs in group 2 had adverse effects. Serum concentrations of itraconazole were positively correlated with serum alkaline phosphatase and alanine aminotransferase activities. Our findings indicate that itraconazole administered at a dose of 5 mg/kg/d is the drug of choice for blastomycosis in dogs.     

Dermatophytic pseudomycetomas in four cats

The aim of this retrospective study was to describe the clinical characteristics and treatment of four cats with dermatophytic pseudomycetoma. Four Persian cats, one female and three males, with age ranging from 1.4 to 5 years, were diagnosed with dermatophytic pseudomycetoma by histological examination and fungal culture. Wood's lamp examination revealed positive fluorescence of hairs in all four cats. Characteristic skin lesions consisted of multifocal, raised, firm and nodular to dome-shaped lesions varying in size from 1 to 8 cm in diameter, with ulcers or fistulas in some of the lesions. One cat was treated and cured with 3 months of oral itraconazole; lesions completely regressed, and at the time of writing there has been no recurrence. One cat was treated with surgical excision alone, and recurrence of lesions occurred after a disease-free interval of 15 months. Two cats were treated with surgical excision and systemic itraconazole therapy. Itraconazole therapy was started 1-2 months before surgery and continued for 3 months after surgery. Surgical margins were wide in both cats, and underlying adipose tissue and/or deeper fascia was removed. One cat relapsed, but had a disease-free interval of 18 months. The other cat has been disease free for 32 months. This case series suggests that aggressive, wide surgical excision and concurrent oral itraconazole are highly beneficial in treating dermatophytic pseudomycetoma in cats.     

Principles of treatment for feline lymphoma

Lymphoma is the most commonly diagnosed neoplasm in cats. As feline leukemia virus antigenemia has decreased over the past 15 years, there has been a profound shift in the presence, signalment, and frequency of sites of feline lymphoma in North America. There is variation in anatomic classification systems, but most studies have divided lymphoma into four groups: alimentary, mediastinal, multicentric, or extranodal. Clinical signs and common differential diagnoses for each of the forms are described. Staging allows for evaluation of the extent of disease. As in the dog, lymphoma is a systemic disease in the cat, and chemotherapy is the treatment of choice for most forms. Exceptions are described. In contrast to canine lymphoma, feline lymphoma is generally more challenging and frustrating to treat than canine lymphoma. Response rates are lower, and remission duration is shorter. Fortunately, cats treated with chemotherapy tend to have less toxicity than dogs. Positive prognostic factors are feline leukemia virus-negative, clinically well at time of diagnosis, and response to therapy. Achieving a complete remission is prognostic for survival. Unfortunately, response cannot be predicted before treatment.     

Efficacy of itraconazole as a combined continuous/pulse therapy in feline dermatophytosis: preliminary results in nine cases

This study evaluated the efficacy of itraconazole as a combined continuous/pulse therapy for feline dermatophytosis. Nine cats with dermatophytosis caused by Microsporum canis were treated with itraconazole at 10 mg kg(-1) orally once daily for 28 days and then on an alternate week regimen (1 week off, 1 week on) at the same dosage. Cats were re-evaluated by physical examination and fungal culture at days 28, 42, 56 and 70 if necessary. Treatment was stopped when two consecutive negative fungal cultures were obtained. Eight cats were cured after 56 days, with two negative cultures obtained at days 28 and 42. In one case, a positive culture was obtained at day 28, but negative cultures were achieved at days 42 and 56. This protocol appears to be effective in the treatment of feline dermatophytosis, although these preliminary results should be confirmed by a controlled study.     

Feline cryptococcosis: impact of current research on clinical management

DISEASE SUMMARY: Cryptococcosis, principally caused by Cryptococcus neoformans and Cryptococcus gattii, is the most common systemic mycosis of cats worldwide. Cats may be infected following inhalation of spores from the environment, with the nasal cavity suspected as being the initial site of colonization and subsequent infection. Other sites of infection in cats are the skin, lungs, lymph nodes, central nervous system (CNS), eyes and, occasionally, periarticular connective tissue. Cryptococcosis can be diagnosed using serology (antigen testing), cytologic examination of smears, histopathology or culture. Treatment of localized disease is generally successful using azole antifungal drugs; however, cats with CNS involvement or disseminated disease require additional treatment with amphotericin B, with or without flucytosine. The prognosis is variable, depending on host and pathogen factors. Some cats require long-term (>1 year) treatment or indefinite therapy. PATIENT GROUP: Cats of any breed, gender and age may be affected. Retroviral status does not appear to be a risk factor for developing cryptococcosis and indoor cats are not protected from disease. GLOBAL IMPORTANCE: Feline cryptococcosis occurs worldwide, but is most frequently reported in Australia, western Canada and the western United States. Species and molecular type vary in different geographical regions and may affect clinical presentation and antifungal susceptibility patterns. CLINICAL CHALLENGES: Serologic tests that detect cryptococcal antigen in serum are sensitive and specific, but false negatives can occur in cats with localized disease. Long-term drug therapy can be expensive and has the potential for toxicity. The extent to which the pathogenicity and antifungal susceptibility is affected by molecular type is currently under study. EVIDENCE BASE: This review draws on recent literature relating to epidemiology, CNS involvement and advanced diagnostic imaging to update clinicians regarding research findings relevant to clinical practice.     

Four cats with fungal rhinitis

Fungal rhinitis is uncommon in the cat and cases of nasal aspergillosis-penicilliosis have been rarely reported. Signs of fungal rhinitis include epistaxis, sneezing, mucopurulent nasal discharge and exophthalmos. Brachycephalic feline breeds seem to be at increased risk for development of nasal aspergillosis-penicilliosis. Computed tomography (CT) imaging and rhinoscopy are useful in assessing the extent of the disease and in obtaining diagnostic samples. Fungal culture may lead to false negative or positive results and must be used in conjunction with other diagnostic tests. Serological testing was not useful in two cats tested. The cats in this study were treated with oral itraconazole therapy. When itraconazole therapy was discontinued prematurely, clinical signs recurred. Hepatotoxicosis is a possible sequel to itraconazole therapy.     

Thrombolytic Therapy in Dogs and Cats

Objective: To review the thrombolytic agents most commonly used in humans, their mechanisms of action, potential uses, adverse effects, and reports of their use in dogs and cats.
Human data synthesis: Thrombolytic agents avaliable in human medicine include streptokinase, urokinase, tissueplasminogen activator (t-PA), single-chain urokinase plasma activator (scu-PA) and anisoylated plasminogen-strep-tokinase activator complex (APSAC). These agents were originally used for the management of proximal deep vein thrombosis and severe pulmonary embolism but more recently, use of these drugs has been extended to include the treatment of acute peripheral arterial disease, cerebrovascular disease (stroke) and acute coronary thrombosis. The most predictable side effect associated with the use of thrombolytic therapy is hemorrhage.
Veterinary data synthesis: Clinical experience with thrombolytic agents in small animals is limited to streptokinase and t-PA. It is possible, that as in humans, canine and feline patients with PTE and right ventricular dysfunction may benefit from thrombolytic therapy but there are no veterinary studies to support this theory to date. Successful use of streptokinase has been documented in a small number of canine patients with systemic thromboembolism. ⁶³ Thrombolytic therapy is relatively efficacious in cats with aortic thromboemboli but is associated with a high mortality rate. ^59,60,64 With regard to use of t-PA in veterinary medicine, the small number of animals treated with varying protocols makes it impossible to provide safe and effective dose recommendations at this time.
Conclusions: Future goals for thrombolytic therapy in veterinary medicine include determination of more specific clinical indications, as well as design of effective protocols that minimize mortality and morbidity.