Antifungal

Question 1

Which of itraconazole, fluconazole, ketoconazole, griseofulvin and terbinafine has the lowest MIC for M. canis and T. mentagrophytes?

Answer 1

Terbinafine

Question 2

What molecule gives its resistance to sporothrix against terbinafine ?

Answer 2

Melanins: pyomelanin and eumelanin

Question 2

How do antifungal agents (example ketoconazole) help decrease pruritus?

Answer 2

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

Question 3

Name topical antifungal treatments

Answer 3

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

Question 4

What is the MOA of lime sulfur

Answer 4

Unknown
It is fungicidal on contact due to formation of hydrogen sulphide + its is keratolytic

Question 5

Have oral ulcers been reported with lime sulfur treatment and if yes why?

Answer 5

NO
But it has been documented in shelter cats- it is thought that ulcers are actually associated with upper respiratory infections + presumed dilution error

Question 6

What are the cutaneous adverse effects of lime sulfur?

Answer 6

Drying of the footpads, loss of hair on the ears, drying of the hair coat, yellow discoloration of white haired cats

Question 7

Enilconazole rinses have been approved in which species?

Answer 7

Cats (only in France), dogs, cattle, horses

Question 8

What are adverse effects of enilconazole rinses?

Answer 8

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

Question 9

How does the chlorhexidine work?

Answer 9

It is a biguanide compound. Low concentrations affect the cell membrane integrity and high concentrations result in congealing of cytoplasm.

Question 10

How do essential oils work?

Answer 10

They result in fungal cell wall damage by slowing growth and/or destruction of the intracellular organelles

Question 11

What is Pythium oligandrum and how does it work?

Answer 11

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

Question 12

What are the current recommendations for topical treatment of dermatophytosis in cats and dogs?

Answer 12

Twice weekly – lime sulfur, enilconazole or chlorhexidine+ miconazole shampoos

Question 13

What is the MOA of itraconazole?

Answer 13

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

Question 14

Because of itraconazole’s high lipophilic properties, in which tissues it accumulates?

Answer 14

Adipose tissue and sebaceous glands

Question 15

What are adverse effect of itraconazole?

Answer 15

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

Question 16

What are side effects of ketoconazole?

Answer 16

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

Question 17

For what is fluconazole primary used and most common side effects ?

Answer 17

For treatment of systemic mycoses
Vomiting, diarrhoea and dose-dependent elevated ALT

Question 18

What are the adverse effects of terbinafine?

Answer 18

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

Question 19

What is the MOA of terbinafine?

Answer 19

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)

Question 20

What are side effect of griseofulvin?

Answer 20

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)

Question 20

What is MOA of griseofulvin?

Answer 20

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

Question 21

What is MOA of lufenuron?

Answer 21

-it is a benzoylphenyl urea drug that disrupts chitin synthesis
-chitin is a component of exoskeleton of arthropods and outer cell wall of fungi

Question 22

Live T. verrucosum or M. canis vaccines given 2x and then challenged by infectious agent had similar results in dogs?

Answer 22

NO, dogs vaccinated with M. canis did not develop the disease (only mild scaling at challenged site) while dogs received T. verrucosum vaccine did !

Question 23

Foxes vaccinated (2x) and then challenged. Did they developed the disease?

Answer 23

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

Question 24

Do kittens develop antibodies against M. canis vaccine and are they protective ?

Answer 24

Yes, they develop IgG and IgM , but the are NOT PROTECTIVE against infection!

Question 25

Have there been studies on effective use of commercial vaccines for the treatment of feline dermatophytosis?

Answer 25

Yes (inactivated M. canis vaccine 2 x 15 days intervals) – remission occurred within 15 days of vaccination

Question 26

What is the name of the infective propagule of dermatophyte fungi?

Answer 26

Arthroconidium
-it forms as a result of segmentation and fragmentation of existing hyphae
-shed arthroconidia and fragmented/shed hairs are source of environmental contamination

Question 27

How long are dermatophytes viable in the environment

Answer 27

T. schoenlenii- at room temp 18 months, to 4.5 years
T. Verrucosum and T. equinum- viable under lab conditions for 4.5 years

Question 28

Name antifungal disinfectants used for environmental decontamination?

Answer 28

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

Question 29

Name zoonotic diseases that are at greatest concern for high-risk clients?

Answer 29

Bartonella
Campylobacter jejuni
Campylobacter canimorsus
Cryptosporidium
Dermatophytosis (M. canis, T. mentagrophytes)
Giardia
Salmonella spp.
Pasteurella multocida
Toxoplasma gondii