W9 Management of Fungal Infections

Question 1

What is the basic function of antifungal agents?
also known as?

Answer 1

Antifungals kill or stop the growth of fungi.
They are also called antimycotic agents.

Question 2

Azole Antifungals
Triazoles:
What are some examples? (2)

Answer 2

1. Fluconazole
   * Very well absorbed after oral administration.
   * Good penetration into the cerebrospinal fluid.
   * Excreted largely unchanged in the urine and can be used to treat candiduria.
2. Itraconazole
   * Active against dermatophytes.
   * Capsules require an acid environment in the stomach for optimal absorption.
   * Associated with liver damage and should be avoided or used with caution in patients with liver disease; (fluconazole is less frequently associated with hepatotoxicity.)

• Also, Posaconazole and Voriconazole

=3 Nitro groups

Question 3

Azole Antifungals
Imidazoles:

Answer 3

• Clotrimazole, econazole nitrate, ketoconazole, and tioconazole.
  -Local treatment of vaginal candidiasis and for dermatophyte infections.
• Miconazole
  -Used locally for oral infections; it is also effective in intestinal infections.
  -Systemic absorption may follow use of miconazole oral gel and may result in significant drug interactions.

Question 4

Polyene Antifungals
What are some examples? (2)

Answer 4

1. Amphotericin B
   * Not absorbed when given by mouth.
   * Intravenous infusion is used for the treatment of systemic fungal infections
   * It is highly protein bound and penetrates poorly into body fluids and tissues.
   * When given parenterally amphotericin B is toxic and side-effects are common.
   * Lipid formulations of amphotericin B (Abelcet® and AmBisome ®) are significantly less toxic
   * Lipid formulations are more expensive.
   * Test dose is advisable before a new course of treatment.
   -A small amount administered for about 10 minutes and then stopped and the patient
   observed carefully
2. Nystatin
   * Not absorbed when given by mouth.
   * Used for oral, oropharyngeal, and perioral infections by local application in the mouth.
   * Nystatin is also used for Candida albicans infection of the skin

Question 5

What are examples of Echinocandin Antifungals?

Answer 5

Anidulafungin, caspofungin and micafungin.
* Only active against Aspergillus spp. and Candida spp.
* However, anidulafungin and micafungin are not used for the treatment of aspergillosis.
* Echinocandins are not effective against fungal infections of the CNS.

Question 6

What are some other antifungals?

Answer 6

1. Flucytosine
   * Used with amphotericin B in a synergistic combination.
   * Bone marrow depression can occur which limits its use, particularly in HIV-positive patients; weekly blood counts are necessary during prolonged therapy.
   * Resistance to flucytosine can develop during therapy and sensitivity testing is essential before and during treatment.
2. Griseofulvin
   * Effective for widespread or intractable dermatophyte infections
   * Superseded by newer antifungals, particularly for nail infections.
   * Duration of therapy is dependent on the site of the infection and may extend to a number of months.
3. Terbinafine
   * Drug of choice for fungal nail infections and is also used for ringworm infections where oral treatment is considered appropriate

Question 7

What is Aspergillosis?

Answer 7

• Caused by Aspergillus species, which is found in soil.
• Inhalation of the aerosolised spores causes the infection.
• Mostly affects immunocompromised patients (e.g., stem cell transplant recipients,
  prolonged severe neutropenia, immunosuppressive therapy).
• Symptoms include fever, cough, and pleuritic pain (sharp pain when breathing)
• First line: Voriconazole
  -Initially 200 mg every 12 hours for 2 doses, then 100 mg every 12 hours (inc. if >40kg)
• Second line: Amphotericin B
  -3 mg/kg once daily
• Early diagnosis and therapy significantly improve prognosis

Question 8

What is Candidiasis?

Answer 8

• Candida are considered normal flora in the
  gastrointestinal and genitourinary tracts in humans, they are capable of local infection of mucous membranes and also CNS ifections
• Many superficial infections covered in Year 1
  -Oral infection
  -Vaginal infection

Question 9

Fluconazole has good penetration into cerebrospinal fluid?
Amphoterin B works well when given orally?
Miconazole oral gel is not systemically absorbed?

Answer 9

Yes
No
No

Question 10

Oral Thrush: (y1 knowledge)
What are the Symptoms?
Treatment?
Signs for GP referral?

Answer 10

Can be discomfort or asymptomatic
Generalised erythema, loss of taste, unpleasant taste in the mouth, white patches that can be wiped off leaving behind red patches

Topical miconazole for 7 days, and continue treatment for 7 days after symptoms resolve IF using miconazole oral gel and 2 days if using Nystatin

Miconazole oral gel- first-line. Do not issue to people using interactive medicines e.g. Warfarin. Apply gel directly to affected area with clean finger, leave in contact with the mucosa for as long as possible. Give after food. Do not eat/drink for 30 mins after using the gel or liquid.

Nystatin oral suspension 100,000u/ml- second-line (warfarin pt etc). Dose is 1ml FOUR times a day for adults and children > 4 weeks of age. Use the dropper to place the liquid inside the mouth onto the affected areas. Only nystatin should be given due to high cost of generic preparation.

Refer:
- symptoms have not resolved after 7 days
-difficulty/pain on swallowing
- no obvious precipitant e.g. steroid inhaler, recent broad-spectrum abx, diabetes, dentures
- immunocompromised
- poorly controlled diabetes
- single red/white plaque that cannot be rubbed off (dentist)

Question 11

Oral thrush: What are the counselling points? (y1 knowledge)

Answer 11

• Maintain good dental hygiene
• Stop smoking if applicable
• Provide counselling advice if pt is on ICS: Rinse mouth with water after inhalation of a dose may be helpful
• In babies and young children it is important to apply a little at a time to try avoid the back of the mouth to reduce the risk of choking

Question 12

What is vaginal candidiasis?

Answer 12

*Common yeast infection, known as thrush
*Caused by Candida albicans
*Usually harmless, but can be uncomfortable and recurrent
*NOT a sexually-transmitted infection (STI)
*However, if infected, the patient’s partner may also have it and need treatment too

Question 13

Vaginal Candidiasis
What are the Symptoms?

Answer 13

Itch (pruritis) around the vagina
-Intense and burning in nature
-Skin may be excoriated and raw from scratching if severe
-Check this is not due to using any new toiletries- could be dermatitis not thrush
*Vaginal discharge
-Normal= thin and watery, no smell
-Candidiasis= white/cream-coloured, thick like cottage cheese, sometimes an unpleasant smell but not always
-Bacterial infection= yellow/green-coloured, strong foul odour
*Vaginal soreness
*Dysuria (pain on urination)
*Dyspareunia (painful sexual intercourse)

Question 14

What are the Risk factors of Vaginal Candidiasis?

Answer 14

*The yeast likes to grow in warm, moist conditions and develops if the balance of vaginal bacteria changes
*Age= Most common in women of childbearing age due to low vaginal pH and the presence of glycogen
*Recently taken a course of antibiotics
*Pregnancy= Attributable to hormonal changes causing INC glycogen
*Diabetes (especially if poorly controlled)
*Weakened immune system E.g. because of HIV or chemotherapy

Question 15

How can you prevent vaginal candidiasis?

Answer 15

• Dry area properly after washing
• Avoid tight/nylon tights or underwear
  -Wear cotton underwear instead as more airy
• Avoid perfumed soaps and shower gels, vaginal douches and deodorants, and foam baths
  -These strip away protective lining of vagina
  *Wipe front to back after bowel motions
  -Candida may be transferred from bowel

Question 16

Vaginal Candidiasis- Management
What formulations are used?

Answer 16

Managed with azole antifungals:
1. Topical vaginal cream
2. Pessary
3. Oral capsule
(Canisten)

*No one option better than other- all equally effective in managing infection.
*Usually decided based on patient preference
*Some OTC products available as a mixture of formulations-to treat infection and provide symptomatic relief
*Offer treatment for free via Common Ailments Scheme

Question 17

Management of vaginal thrush- Topical vaginal cream (External cream)
What drug is used?
Common SE?
How often to apply?

Answer 17

*Clotrimazole 2% cream (Canesten®)
*Used for immediate symptomatic relief of itch
*Apply thinly to vulva and surrounding area BD-TDS until symptoms disappear
*Common side effects: Itching/burning sensation
*Can damage latex contraceptives- use alternative precautions for at least 5 days after using product
*Need to be motivated to continue using it if using alone

Question 18

Management of vaginal thrush- Topical vaginal cream (Internal cream)
What drug is used?
Common SE?
How often to apply?

Answer 18

*Clotrimazole 10% cream (Canesten®)

*Administer intravaginally using the applicator supplied
*One-off treatment, best administered at night

*Common side effects: Itching/burning sensation
*Convenient but some women uncomfortable with the formulation
*Can damage latex contraceptives- use alternative precautions for at least 5 days after using product
*Not to be used during periods- may wash out

Question 19

Management of vaginal thrush: Pessary
What drug is used?
Common SE?
How often to apply?

Answer 19

• Clotrimazole 500mg, 200mg or 100mg (Canesten®)
• Administer intravaginally as high as possible using the applicator supplied
• 500mg pessary: One-off treatment at night, can be repeated in 7 days if infection returns (only this is available via Common Ailments Scheme)
• 200mg pessary: One pessary daily at night for 3 days
• 100mg pessary: Two pessaries daily at night for 3 days OR one pessary daily at night for 6 days
• Common side effects: Itching/burning sensation
• Convenient but some women uncomfortable with the formulation
• If using longer course, must be motivated to complete course
• Can damage latex contraceptives- use alternative precautions for at least 5 days after using product
• Check patient understanding with regards to application
• Not to be used during periods- may wash out
• Do not use tampons/intravaginal douches/spermicides etc during

Question 20

Management of Vaginal thrush: Oral
capsule
What drug is used?
Common SE?
How often to apply?

Answer 20

• Fluconazole 150mg oral capsule
  (Canesten®)
• One-off dose, to be swallowed whole
• May take 12-24 hours for symptoms to
  improve
• Key drug interactions: warfarin, statins, phenytoin,rifampicin, ciclosporin and
  theophylline.
• Single dose may not affect drug levels too much but will need to refer to GP.
• Side effects are mild and transient; include nausea, abdodiscomfort, flatulence and diarrhoea.
• Convenient and acceptable formulation

Question 21

Candidiasis symptoms in males (candidal
balanitis)
Symptoms?
Management?

Answer 21

*Male may catch infection from a female partner
*May be asymptomatic
*Symptoms may include:
* Irritation, burning and redness around the head of the penis and under the foreskin
* White/cream-coloured discharge, thick in consistency like cottage cheese
* Discharge which may or may not have an unpleasant smell
* Difficulty pulling back the foreskin

*Will only usually treat partner if they are symptomatic (area up for debate)
*Management: Azole external cream BD for 6 days or oral fluconazole STAT

Question 22

Candidiasis- When to refer to GP
(Oral and Vaginal)

Answer 22

Recurrence of symptoms- to confirm diagnosis:
* Allergic to antifungals
* Pregnant or breast feeding
* Immunocompromised
* More than 2 thrush attacks in previous 6 months
* Previous exposure to STI or partner with STI
* Women aged under 16 or over 60
* Abnormal/irregular vaginal bleeding
* Blood-stained vaginal discharge // Foul smelling discharge
* Vulval or vaginal sores/blisters/ulcers
* Associated lower abdo pain or dysuria
* Adverse effects related to treatment (redness/irritation/swelling)
* No improvement within 7 days of treatment

• OTC licensing of candidiasis products reflect these referral criteria

Question 23

Systemic candidiasis

Answer 23

• Infection of blood or other normally sterile sites
• These may include retina, kidney, liver and spleen,bones, and the central nervous system.
• Often seen with the use of central venous catheter
• Symptoms include fever, tachycardia or tachypnoea
• Firstline: caspofungin (or other echinocandin)
• Alternatively: fluconazole
• Second line: amphotericin B

Question 24

Cryptococcosis

Answer 24

• Caused by Cryptococcus species, commonly found in bird excrement (especially pigeon).
• The lungs are primarily affected. However, further symptomatic involvement may occur in the brain.
• Symptoms include pyrexia, a productive cough, dyspnoea, chest pain, weight loss, and fatigue.
• Treatment options: fluconazole, itraconazole or amphotericin B

Question 25

Cryptococcal meningitis

Answer 25

• Typically presents as a progressive, life-threatening, chronic or subacute meningitis.
• Occurs most commonly in immunosuppressed individuals and is often accompanied by systemic involvement.
• Symptoms include progressive headache, severe headache, meningismus
• Treatment: amphotericin B by intravenous infusion and flucytosine by intravenous infusion for 2 weeks, followed by fluconazole by mouth for 8 weeks

Question 26

What is Histoplasmosis?
Symptoms?

Answer 26

The fungus proliferates well in soil contaminated with bird or bat droppings; therefore, exposure toHistoplasma capsulatum
Histoplasmosis infection is usually asymptomatic or minimally symptomatic
Symptoms can include fever, headache or dyspnoea
Treatment: Itraconazole
Treatment in severe infections: Amphotericin B (followed by itraconazole)

• In some people, the fungus spreads to the eyes.
• Abnormal blood vessels can form, which can affect vision.
• Without treatment, vision loss can become permanent.
• Care will likely not include antifungal medications.
• Fungus causes ocular histoplasmosis, not the same as having a fungal infection

Question 27

Skin and nail infections

Answer 27

• Mild symptoms treated OTC
• Difficult to treat such as in infections of the nails and of the scalp may require POM
  treatment
• Scalp
• Tinea capitis is treated systemically; additional topical application of an antifungal may reduce transmission.
• Oral Griseofulvin
• Ketoconazole 2% shampoo
• Nail
• Onychomycosis is treated systemically (more effective than topical therapy).
• First line: Terbinafine
• Second line: Itraconazol

(Nails are treated systemically now but traditionally treated topically)

Question 28

Skin infections (Fungal)

Answer 28

• Ringworm is a fungal infection that
  presents as a circular rash
• Spread by person-person / person-
  animal contact
• Ringworm of the scalp is rare and
  should be referred
• Fungal nail infections should be
  referred as system antibiotics usually
  required
• Athlete’s foot is a fungal foot infection
  usually spread by person-person contact or from shared towels, changing rooms etc.

Question 29

Skin infections (Fungal) – Treatment

Answer 29

• Ringworm and athlete’s foot can be treated OTC with topical antifungals
• Imidazoles, e.g. miconazole cream (Daktarin®), are the
  usual first line treatment for ringworm and are also used for
  athlete’s foot
• Itraconazole and terbinafine (an allylamine) are also used
  OTC in athlete’s foot treatment
• Powder and spray formulations are commonly used for
  athlete’s foot
• When to refer
• Treatment failure (>2 weeks)
• Bacterial infection
• Diabetic patients
• Involvement of the nail

Question 30

Common Fungal Skin Infections

Answer 30

Body and groin - Diagnosis:
* History of scaly, itchy skin.
* Folds of skin
* Single or multiple red or pink, flat or slightly
raised ring-shaped patches of varying sizes which enlarge outwards.
* Red, scaly advancing edge and a clear central area
* They are usually asymmetrical in distribution.
* There may be larger lesions and joining of lesions.

Body and groin – Differential Diagnosis:
* Eczema
* Pityriasis
* Psoriasis

Body and groin - Treatment:
* Topical antifungal cream (e.g. an imidazole)
* May need repeating
* Consider a mildly-potent corticosteroid, if there is inflammation
* Hydrocortisone 1% cream to be applied once daily for a maximum of 7 days
* In severe infection: Terbinafine 1st line

Question 31

Immunocompromised patients

Answer 31

• Immunocompromised patients are at particular risk of fungal infections and may receive antifungal drugs prophylactically
• Oral triazole antifungals are the drugs of choice for prophylaxis
• Micafungin can be used for prophylaxis of candidiasis in patients undergoing haematopoietic stem cell transplantation