Infectious causes of feline diarrhea (Proceedings)
Infectious causes of gastrointestinal disease in the cat are important for two reasons. The first is clearly the impact on the health of the cat itself.
Histoplasmosis: Epidemiology
• Histoplasma capsulatum
o Worldwide distribution
o Most prevalent: Missouri, Ohio, Mississippi River Valleys
o Most commonly diagnosed human systemic mycosis
o Sporulation enhanced in presence of bird and bat guano
o Very environmentally resistant
o Contaminated soil present >15 years after removal
• Infection
o Inhalational
o Ingestion
o (Disrupted skin)
• Pathophysiology
o Phagocytosis: RE system
o Dissemination or pulmonary disease?
o Lymphatics/hematogenously
• Clinical presentation
o Dogs
¢ <4 years of age
¢ Gender variable
¢ Pointers? Brittany spaniels?
o Cats
¢ 2nd most commonly diagnosed
¢ Gender variable
¢ Persians
• Clinical presentation
• Pulmonary
• Acute: uncommon (contrast to human)
• Chronic: canine
• Disseminated
o Chronic Pulmonary
¢ Mild cough
¢ Weight loss/inappetance
¢ Hilar lymphadenopathy
o Disseminated : feline
¢ GI NOT common
¢ Bony lesions (lysis)
¢ Weight loss
¢ Fever
¢ Lymphadenopathy
¢ Pulmonary: miliary interstitial, not lymphadenopathy
¢ Chorioretinitis
¢ Hepatic/icterus
• Diagnosis
o Travel history (not necc recent)
o Demonstration of organism
o 2-4 um
o Shrinkage of capsule
o Intracellular (or free)
o Lymph node aspirate CBC Bone marrow Rectal scraping (dogs)
o Diagnosis
¢ Serology (CF): false negatives and positives
¢ 9 of 11 negative in dogs
¢ 10 of 13 in cats
o Antigen detection
¢ ELISA
• MiraVista Labs
• Test of choice: urine humans
• No veterinary data as of yet
• Treatment
o Mild pulmonary
o Spontaneous recovery?
o Moderate pulmonary
¢ Itraconazole 10 mg/kg q 24
• Remember dose dependent side effects
• Can restart at 1/2 dose 7-10 days
¢ Fluconazole?
8226; Less effective in humans
8226; 2 mg/kg q 24
o Severe pulmonary
¢ Amphotericin B in conjunction with ITZ
¢ Steroids? As for B. dermatiditis
8226; Cryptococcosis
o Dog and cat
o Nasal most common
o Systemic occurs-Extension
o Ocular
o CNS
o Lympadenopathy
o Pleural effusion
• Location
o Worldwide
o Hot spots
o Australia
o Vancouver
o Southern California
• Diagnosis
o Organism demonstration
o Cytology
o Histology
o Culture
o Antigen testing
o Antibody serology
o Unreliable
• Static drugs-Fungal infections
o Fluconazole
o 28/29 cats responded
o Itraconazole
o 16/28 cats responded
o Cidal drugs
Combination therapy: AmB + Flucytosine
Sporothrix schenkii: cats
o Worldwide distribution
o Sporotrichosis
o Treatment:
o itraconazole administered orally at 5-10 mg/kg once daily
o 30 days beyond complete resolution of detectable Blastomyces dermatitidis
o Dimorphic fungus: thermally dependant
o Mycelial: soil/infectious
o Yeast: host/non-infectious
• Epidemiology
o Soil and decaying wood
o Recently disturbed
o Attic/basement
o Hunters (man and dog)
o January and Aug-Oct
o Proximity to a body of water
• Pathogenesis
o Inhalation of mycelial phase
o Increase in temperature → yeast phase
o Complement response: phagocytes/improved growth in vitro
o Melanin like pigment production: increased virulence
• Clinical disease: pulmonary 85%
o Classic snowstorm
o Diffuse miliary to nodular interstitial
• Clinical disease: ocular 30-40%
o Anterior uveitis
o Panophthalmitis
o Chorioretinitis
o Retinal detachment
o optic neuritis
o Ocular disease: to enucleate or not?
o Positive response to treatment (ITZ)
o Posterior segment only best prognosis
o 31/36 (86%) eyes had evidence of B. dermatitidis organisms
• Other systems
o Bone
o Distal appendicular
o Testes, CNS, kidney, nasal passages
o Skin
o Ulcerative
o Granulomatous
o Subcutaneous
o Calcinosis cutis (treatment?)
o Hypercalcemia: Granulomatous disease
o Diagnosis
o Cytology/histopath
o 10-20 um
o Basophilic
o Broad based
o FNA
¢ Lymph node Cutaneous lesions joints lungs Impression smear: (BAL/TTW) CSF
o Serology
¢ AGID (agar gel immunodiffusion)
¢ Low negative predictive value (high rate of false negatives)
¢ 17-40% sensitivity
¢ greater specificity than in human
¢ Seroconversion slow
¢ Persistence of positive (previous infection)
o Antigen detection: ELISA
¢ cell wall
¢ cross-reactivity: humans: histoplasmosis (coccidiomycosis)
¢ urinary sensitivity 93% in humans
¢ Veterinary EIA
¢ Dogs: 93% sensitivity urine, 87% serum
o cross reactivity????????
o decline over treatment
• Treatment/prognosis
o Itraconazole
o historically drug of choice
o replacement with fluconazole?
o NOT as effective in humans/in vitro (65%)
o poor response? consider TDM
• Treatment
o Both of us are eukaryotes
o targets that we don't have are few and far between
o ergosterol: traditional target (vs. cholesterol)
• Targets for therapy
• Classes
• Polyenes
o amphotericin B
• Azoles
o imidazoles (ketaconazole)
o triazoles (itraconazole)
• Echinocandins
o caspofungin
• Flucytosine
• Polyenes: amphotericin B
o dosing
o cumulative dose (as an infusion in D5W over 1-4 h):
o dogs: 4-8 mg/kg (3x weekly at 0.25-0.75 mg/kg IV)
o cats: 4-6 mg/kg (3x weekly at 0.1-0.25 mg/kg IV)
o side effects
¢ fever myalgia chills rigor
o nephrotoxicity
¢ mechanisms to decrease side effects
¢ innate immune/infusion related
¢ pre-treatment
¢ dyphenhydramine (0.5 mg/kg)
¢ aspirin (10 mg/kg PO: caution GI and cats)
¢ physiologic glucocorticoids
¢ slower infusion (4-6 hrs)
¢ Amphotericin B
¢ mechanisms to decrease side effects
¢ nephrotoxicity
¢ vasoconstriction
¢ saline diuresis prior to administration
¢ sodium loading (Na depletion worsens)
¢ tubulotoxicity
¢ monitoring of K+, BUN, creatinine
¢ delay next dose until normalizes
¢ modulate accumulation in kidneys: vary formulations
o Abelcet: lipid complexed
¢ dosing
¢ no saline preloading necessary
¢ diluted in D5W to 1 mg/mL
¢ infuse over 1-2 hours
¢ dogs: 24-27 mg/kg (2-3 mg/kg IV 3x/weeek)
¢ cats: 12 mg/kg (1 mg/kg IV 3x/week)
¢ continue to monitor BUN, creat, K+
o liposome encapsulated (AmBiosome)
¢ true liposomal encapsulation
¢ smaller than lipid complex
¢ lower incidence of infusion related side effects in humans as compared to lipid complex
¢ dosing? beagles: 4 mg/kg/d
• pharmacokinetics: fluconazole
o bioavailability NOT affected by gastric pH
o weakly protein bound
o highly water soluble
o distribution (poorer accumulation but good barrier penetration)
o urine, CSF, ocular,
¢ blood prostate, blood ocular
o minimally metabolized
o availability of a generic ($$$)
• Azoles
o side effects
¢ dose related (ulcerative dermatitis)
¢ similar across the class
¢ triazoles less potent inhibitors of cP450
¢ fewer drug interactions
¢ dose reduction for fluconazole in azotemia
¢ transaminase activity
¢ spontaneous remission
¢ rare after first 3 months
¢ associated with clinical signs: discontinue
¢ thrombocytopenia
o Itraconazole (Sporonox)
o dogs: blastomycosis
¢ 5 mg/kg (do not increase, no improvement in efficacy)
o dogs: 10 mg/kg (for other mycoses if severe)
¢ significant incidence (10%) of ulcerative dermatitis
¢ usually reversible if recognized
¢ can cause significant necrosis and sloughing
cats: 10 mg/kg PO or IV
¢ GI side effects decreased by dividing into BID
• Fluconazole (generics)
o less efficacious based on in vitro and human studies: B. dermatitidus, H. capsulatum
o drug of choice for cryptococcosis
o 1st generation triazoles
o Fluconazole (generics)
o dogs: 2.5-10 mg/kg PO or IV q 24 h
o cats: 10 mg/kg PO or IV q 24h (50 mg/cat <8 pounds, 100 mg/cat >8 pounds)
o better penetration: eye, CNS
• Cidal drug
• Amphotericin B
¢ Regular
¢ Lipid complex
¢ Liposome encapsulated
¢ Systemic Fungi
¢ Liposomal Amphotericin B
o 1-3 mg/kg IV, q 1-3 days
o Cumulative dose 12 mg/kg?
o Safe, but expensive!
o If owner refuses, consider SQ protocol
