Antifungal Flashcards
Which of itraconazole, fluconazole, ketoconazole, griseofulvin and terbinafine has the lowest MIC for M. canis and T. mentagrophytes?
Terbinafine
What molecule gives its resistance to sporothrix against terbinafine ?
Melanins: pyomelanin and eumelanin
How do antifungal agents (example ketoconazole) help decrease pruritus?
Ketoconazole: direct antifungal activity against Malassezia. Like bacteria, Malassezia produces substances that are pruritogenic. These substances also may trigger type I hypersensitivity reactions.
block enzyme 5-lipoxygenase. This enzyme involved in formation of inflammatory cytokines such as LTC4
Name topical antifungal treatments
Lime sulfur (calcium polysulfide)- leave on rinse
Enilconazole leave on rinse
Miconazole/chlorhexidine formulations
Chlorhexidine formulations
Miconazole formulations
Terbinafine formulations
Ketoconazole formulations ( no in vivo reports)
Climbazole formulations( no in vivo reports)
Accelerated hydrogen peroxide ( no in vivo reports)
Essential oils
Pythium oligandrum
Focal treatment products
What is the MOA of lime sulfur
Unknown
It is fungicidal on contact due to formation of hydrogen sulphide + its is keratolytic
Have oral ulcers been reported with lime sulfur treatment and if yes why?
NO
But it has been documented in shelter cats- it is thought that ulcers are actually associated with upper respiratory infections + presumed dilution error
What are the cutaneous adverse effects of lime sulfur?
Drying of the footpads, loss of hair on the ears, drying of the hair coat, yellow discoloration of white haired cats
Enilconazole rinses have been approved in which species?
Cats (only in France), dogs, cattle, horses
What are adverse effects of enilconazole rinses?
Slight discoloration of the hair coat, drooling (from min to 1 h), drying of the hair coat, hind limb muscle weakness, increased ALP, was safe in pregnant cats BUT 2 kittens were still-born and 2 failed to thrive
How does the chlorhexidine work?
It is a biguanide compound. Low concentrations affect the cell membrane integrity and high concentrations result in congealing of cytoplasm.
How do essential oils work?
They result in fungal cell wall damage by slowing growth and/or destruction of the intracellular organelles
What is Pythium oligandrum and how does it work?
It is a soil micromycete with mycoparasitic properties and has been used in agriculture to control fungal infections in plants.
-the organism obtains necessary growth nutrients by consuming target fungi
-available in Czech republic
What are the current recommendations for topical treatment of dermatophytosis in cats and dogs?
Twice weekly – lime sulfur, enilconazole or chlorhexidine+ miconazole shampoos
What is the MOA of itraconazole?
It inhibits fungal cytochrome P450 enzyme 14𝝰 demethylase to prevent conversion of lanosterol to ergosterol (ergosterol is vital for maintaining cell wall integrity and activity)
-at low concertation is fungistatic, at high is fungicidal
Because of itraconazole’s high lipophilic properties, in which tissues it accumulates?
Adipose tissue and sebaceous glands
What are adverse effect of itraconazole?
Anorexia, elevations of liver enzymes (ALT, AST) , pale liver on post mortem (but no histo changes) , decreased body weight, vomiting, diarrhoea
+ fatal liver toxicity (median 13.8 mg/kg for 8.5 months)
-not recommended to used in pregnant or nursing animals (embryotoxicity and teratogenicity > 40 mg/kg)
+ cutaneous vasculitis or skin ulcerations→ not completely sure because it may be associated with underlying diseases (deep mycoses), but is commonly seen in dogs receiving ≥10 mg/kg for deep mycoses
What are side effects of ketoconazole?
Depression, inappetence, weight loss, vomiting, diarrhoea, hair coats are dry and rough , teratogenic, excretes in milk , intermittent constipation (dogs)
-increased albumin, Ca, ALP
-not recommended for usage in pregnant or lactating animals
For what is fluconazole primary used and most common side effects ?
For treatment of systemic mycoses
Vomiting, diarrhoea and dose-dependent elevated ALT
What are the adverse effects of terbinafine?
Vomiting, diarrhoea/soft stool, mild elevations in ALT, ALP
-cats: lethargy, anorexia, weight loss + intense facial pruritus and macular to papular skin reactions (histo findings ALLERGIC reaction)
-dogs: periocular swelling, chemosis, conjunctival erythema
What is the MOA of terbinafine?
It inhibits fungal sterol biosynthesis (greater than mammalian sterol biosynthesis)
-it reversibly inhibits the membrane-bound enzyme SQUALENE EPOXIDASE in a concertation- dependent manner which prevents conversion of LANOSTEROL to CHOLESTEROL and/or ERGOSTEROL
-doesn’t effect cytochrome P450
-it’s a synthetic allylamine (developed by chemical modification of naftitine)
What are side effect of griseofulvin?
Teratogen
-pruritus, malaise, anorexia, walking with straddled gait, thick scruffy coat with brown scales and marked erythema
-lethargy, pyrexia, depression, ataxia, upper respiratory infections, leukopenia or pancytopenia (bone marrow hypoplasia)
-FIV + cats: fever, depression, anorexia, diarrhoea, petechia hemorrhages, severe neutropenia
Drug-associated pancytopenia in cats is IDIOSYNCRATIC REACTION (in dog only one case)
What is MOA of griseofulvin?
It inhibits nucleic acid synthesis and cell mitosis by arresting division in metaphase
-interferes with the function of spindle microtubules
-it causes morphological changes in fungal cells and may antagonize chitin synthesis in the fungal cell wall
-isolated form mycelium of Penicillium griseofulvin
What is MOA of lufenuron?
-it is a benzoylphenyl urea drug that disrupts chitin synthesis
-chitin is a component of exoskeleton of arthropods and outer cell wall of fungi
Live T. verrucosum or M. canis vaccines given 2x and then challenged by infectious agent had similar results in dogs?
NO, dogs vaccinated with M. canis did not develop the disease (only mild scaling at challenged site) while dogs received T. verrucosum vaccine did !
Foxes vaccinated (2x) and then challenged. Did they developed the disease?
No, vaccinated animals developed superficial scaling 7-14 days post challenge
Vaccination has a prophylactic effect in some studies (but its not recommended to use it as a prophylaxis in the guidelines). but no clinical response had been seen when vaccine was used a sole therapy but may be useful adjunct therapy
Do kittens develop antibodies against M. canis vaccine and are they protective ?
Yes, they develop IgG and IgM , but the are NOT PROTECTIVE against infection!
Have there been studies on effective use of commercial vaccines for the treatment of feline dermatophytosis?
Yes (inactivated M. canis vaccine 2 x 15 days intervals) – remission occurred within 15 days of vaccination
What is the name of the infective propagule of dermatophyte fungi?
Arthroconidium
-it forms as a result of segmentation and fragmentation of existing hyphae
-shed arthroconidia and fragmented/shed hairs are source of environmental contamination
How long are dermatophytes viable in the environment
T. schoenlenii- at room temp 18 months, to 4.5 years
T. Verrucosum and T. equinum- viable under lab conditions for 4.5 years
Name antifungal disinfectants used for environmental decontamination?
sodium hypochlorite ( bleach) 1:10- 1:100
Enilconazole – spray or environmental fogger
Accelerated hydrogen peroxide
Potassium peroxymonosulfate
Bathroom and general disinfectant with claimed antifungal action
Essential oils- limonene, geranial, neral
Name zoonotic diseases that are at greatest concern for high-risk clients?
Bartonella
Campylobacter jejuni
Campylobacter canimorsus
Cryptosporidium
Dermatophytosis (M. canis, T. mentagrophytes)
Giardia
Salmonella spp.
Pasteurella multocida
Toxoplasma gondii
