It is caused by infection with species of the genus Candida, predominantly with Candida albican
Types: candidiasis Vaginal - a
Presentation: - 1- Itching and irritation in the vaginal area.
1- Candidiasis
2-A burning sensation, especially during intercourse or while urinating
3-Redness and swelling of the area
4-Vaginal pain and soreness 5-Thick, white, odor-free vaginal discharge with a cottage cheese appearance
1-Treatment: 1- mild to moderate symptoms and infrequent episodes of infection
a-Short-course vaginal therapy:
Candidiasis
- one-to-three-day regimen of an antifungal cream, ointment, tablet or suppository -The medication of choice is azole antifungal family: butoconazole, clotrimazole ,miconazole and terconazole .
The oil-based nature of these agents in cream and suppository form can weaken latex condoms and diaphragms
-Side effects : A- slight burning or irritation during application
Candidiasis
B- Single-dose oral medication fluconazole (Diflucan) to be taken by mouth. 2- Treatment for a complicated cases a- Long-course vaginal therapy includes an azole medication in the form of a vaginal cream, ointment, tablet or suppository. The duration of treatment is usually seven to 14 days. b- Multidose oral medication instead of vaginal therapy: two or three doses of fluconazole to be taken by mouth. ***this therapy isn't recommended for pregnant women.
Candidiasis
c- Maintenance therapy: For recurrent infections
- It starts after the initial treatment clears infection
-It include:
I-fluconazole tablets taken by mouth once a week for six months. II- Clotrimazole as a vaginal tablet (suppository) used once a week instead of an oral medication
Candidiasis
b- Oropharyngeal candidiasis
Presentation
I-Children and adults
a-Creamy white lesions on tongue, inner cheeks and on the roof of mouth, gums and tonsils
b-Lesions with a cottage cheese-like appearance
c-Pain
d-Slight bleeding if the lesions are rubbed or scraped
Candidiasis
e- Cracking and redness at the corners of the mouth
f- Loss of taste
II- Infants and breast-feeding mothers
a- white mouth lesions b- infants may have trouble feeding or and irritable.
c- Unusually red, sensitive or itchy nipples
d- Unusual pain during nursing or painful nipples between feedings
Candidiasis
Treatment
A- For infants and nursing mothers
1- A mild topical antifungal medication for baby and mother. Example: miconazole
2- If baby uses a pacifier or feeds from a bottle, rinse nipples and pacifiers in a solution of equal parts water and vinegar daily and allow them to air dry to prevent fungus growth.
3-If mother use a breast pump, rinse any of the detachable parts that come in contact with milk in a vinegar and water solution. Candidiasis
B- For healthy adults and children
1-Eating unsweetened yogurt
2-Taking acidophilus capsules or liquid
Yogurt and acidophilus don't destroy the fungus, but they can help restore the normal bacterial flora in the body.
3-If infection persists, Topical antifungal medication can be used
Candidiasis
C- For adults with weakened immune systems
1-Antifungal medication ( lozenges, tablets or a liquid that can be swish in mouth and then swallow). Example: nystatin.
2-Amphotericin B that can be used when other medications aren't effective.
Candidiasis
C- skin lesion
-Presentation: 1-itching
2- Red and growing skin rash. This rash with discrete borders
3- Rash usually appear on the skin folds, genitals, middle of the body, buttocks, and under the breasts
b-Luliconazole (Luzu) is an imidazole topical cream approved by the FDA in November 2013 for treatment tinea corporis
FDA approves luliconazole for treatment of tinea corporis
2- Dermatophytoses
FDA recently approved the azole antifungal luliconazole 1% cream the first topical azole antifungal agent with a 1-week (rather than 2-week), once- daily treatment regimen for the management of tinea cruris and tinea corporis in adults aged 18 years or older. Luliconazole was also approved for the treatment of interdigital tinea pedis in adults, a regimen that requires a 2-week treatment period.
2- Dermatophytoses
Allylamines (eg, naftifine, terbinafine) - c
2- Severe cases need systemic therapy : griseofulvin, Systemic azoles (eg, fluconazole, itraconazole, ketoconazole)
(athlete's foot ) pedis Tinea - c
It is a dermatophyte infection of the soles of the feet and the interdigital spaces Athlete's foot 2- Dermatophytoses
It occurs most commonly in people whose feet have become very sweaty while confined within tight-fitting shoes.
- Presentation
1- Scaly rash that usually causes itching, stinging and burning.
2- Some cases: blisters or ulcers.
3- Some cases: chronic dryness and scaling on the soles that extends up the sides of the feet
2- Dermatophytoses
- Treatment:
1- Topical treatment:
a- imidazole:clotrimazole, econazole, miconazole, ketoconazole and luliconazole) "Luliconazole, an imidazole topical cream, is applied once daily for 2 weeks "
b- Ciclopirox cream
c- terinafine and naftitine
2- Dermatophytoses
2-oral drugs in severe cases : Itraconazole, Terbinafine, and fluconazole
- Instructions A thin layer of the topical agent applied once or twice a day on affected area for at least two weeks.
4- Fungal nail infections (onychomycosis) Onychomycosis is a fungal infection of the toenails or fingernails.
Causes:
1-Most common cause is Dermatophytes ( Tinea ungum )
2-Candida (yeasts )
3- molds
4- Fungal nail infections (onychomycosis) - Presentation:
There are different classifications of nail fungus depending on type of fungus and manifestation.
- Common symptoms:
1- A painful and erythematous area around and underneath the nail and nail bed
2- Nail thickening, ridging, discoloration, and occasional nail loss
4- Fungal nail infections (onychomycosis) 3-Infected nails may separate from the nail bed.
- Treatment :
1-Topical antifungal: -Topical treatment used for mild to moderate cases -Agents: Amorolfine (Loceryl), Ciclopirox ( Mycoster) .
2-Oral medication: Most effective treatments are terbinafine (Lamisil) and itraconazole (Sporanox)
4- Fungal nail infections (onychomycosis) Oral medication recommended for:
1- DM patients
2- If patient has cellulitis or history of cellulitis
3- If patient has pain or discomfort from nail infection
- These Drugs help growing a new nail free of infection, slowly replacing the infected portion of nail. these medications will be taken for six to 12 weeks, and the end result of treatment seen after the nail grows back completely (It may take four months or longer to eliminate an infection)
4- Fungal nail infections (onychomycosis)
To decrease the adverse effects and duration of oral therapy, topical treatments may be combined with oral antifungal management Most common fungal infection s 5- Aspergillosis
- Commonly affects respiratory tract
- Invasive forms can affect heart, brain and skin
- Drug of choice: Voriconazole
6- Cryptococcosis
- Most common form: cryptococcal meningitis Treatment : amphotericin B and flucytocine for 2 weeks then followed by fluconazole for 8 weeks or until culture is positive
Most common fungal infection s 7-histoplasmosis
Histoplasmosis is an infection caused by breathing in spores of a fungus often found in bird and bat droppings
Antifungal Drugs
I-Azole family:
- M.O.A -Inhibit sterol synthesis in fungal cell membranes, this lead to increase cell permeability and osmotic pressure
- Drugs:
1-ketoconazole (Nizoral) - Systemic Ketoconazole It has slow onset of action and need long duration of therapy
1- ketoconazole - Off-label use :
1- Cushing syndrome :ketoconazole Inhibits steroidogenes process through inhibiting P450 enzymes includes the first step in cortisol synthesis, cholesterol side-chain cleavage, and conversion of 11-deoxycortisol to cortisol
2- Dose Range : 600-800 mg/day PO 1- ketoconazole Tablets are not recommended as first-line treatment; should be used only when other effective antifungal therapy is not effective or tolerated and the potential benefits are considered to outweigh the potential of hepatotoxicity
Usual dose range: - 200-400 mg/day PO 1- ketoconazole Black Box Warnings
A-Hepatotoxicity has occurred with oral use, including some fatalities or requiring liver
B-May cause QT prolongation - Coadministration with dofetilide, quinidine, pimozide, cisapride, methadone, disopyramide, dronedarone, and ranolazine is contraindicated
1- ketoconazole - Ketoconazole can cause elevated plasma concentrations of these drugs (by CYP3A4 inhibition) and may prolong QT intervals, sometimes resulting in life-threatening ventricular dysrhythmias such as torsades de pointes
Most common side effects: - Nausea,vomiting,diarrhea, constipation, and abdominal pain - Rare : hepatotoxicity
Drugs interaction: Enhance anticoagulant effects of warfarin
1- ketoconazole Ketoconazole( nizoral) Potentially Fatal Liver Injury, Risk of Drug Interactions and Adrenal Gland Problems
July 26, 2013 Audience: Internal Medicine, Infectious Disease.
ISSUE: FDA is taking several actionsrelated to Nizoral (ketoconazole) oral tablets, including limiting the drugs use, warning that it can cause severe liver injuries and adrenal gland problems, and advising that it can lead to harmful drug interactions with other medications. FDA has approved label changes and added a new Medication Guide to address these safety issues. As a result, Nizoral oral tablets should not be a first-line treatment for any fungal infection. Nizoral should be used for the treatment of certain fungal infections, known as endemic mycoses, only when alternative antifungal therapies are not available or tolerated. 1- Ketoconazole Topical Ketoconazole
- Indication and dose
1-Seborheic Dermatitis
a-Foam: apply to affected area q12hr for 4 wk
b-Cream: apply q12hr for 4 wk or until clear
c-Shampoo: apply twice weekly for 4 wk with at least 3 days between each shampoo
2-Tinea Versicolor
a-Shampoo: twice weekly for 4 wks allowing 3 days between shampoo
3-Tinea corporis, Tinea Cruris, Tinea pedis Cream: Apply once daily to cover affected area for 2 weeks (6 weeks for tinea pedis)
1- Ketoconazole 1- Ketoconazole
*** When combined with corticosteroid , ketoconazole is useful in treating : Atopic dermatitis, diaper rash, eczema, and psoriasis
2-Fluconazole (Diflucan)
-It achieves good penetration into cerebrospinal fluid so can be used for treating fungal meningitis
- It excreted largely in the urine and can be used for treating candiduria
Drugs interaction: -
1- Avoid concomitant use with cisapride and terfenadine
2- It increases level of phenytoin, warfarin, sulfonylurea and cyclosporine 2-Fluconazole (Diflucan) - Dose: 1-Oropharyngeal & esophageal candidiasis: 200mg , orally on first day then continue 100mg, orally , daily
2-Vaginal candidiasis: 150mg as single dose
3-Cryptoccocal meningitis: 400mg, orally on day 1 then 200mg, orally daily
Negative inotropic effects reported with IV administration; reassess therapy if signs or symptoms of CHF occur during administration
Onychomycosis - 2
Onychomycosis treatment contraindicated in patients with ventricular dysfunction or history of heart failure. 3- Itraconazole (Sporanex) Caution -Discontinue if liver disease develops, and perform liver function tests; readministration discouraged
" Itraconazole is contraindicated for treating onychomycosis in pregnant or intend on becoming pregnant "
Most common side effects - Nausea 4-Voriconazole (Vfend) - Broad spectrum antifungal and used in life threatening infection and refractory cases
Most common side effects: Visual changes (photophobia, color changes, increased or decreased visual acuity, or blurred vision occur in 21%) 4-Voriconazole (Vfend) Warning:
Avoid intense or prolonged exposure to direct sunlight; in patients with photosensitivity skin reactions, squamous cell carcinoma of the skin and melanoma have been reported during long- term therapy 5- Posaconazole - licensed for treatment of invasive cases unresponsive to conventional therapy
-Food increases oral availability so preferred to take the dose with full meal
-Most common side effects nausea & headache
-Drugs interactions: 1-avoid concomitant use with cimetidine, phenytoin, and rifbutin 5- Posaconazole 2- Coadministration with sirolimus; increases sirolimus blood concentrations
Dose oropharyngeal candidiasis -oral suspension: 100 mg , PO BID on Day 1, then 100 mg PO qDay for 13 days
-Refractory to itraconazole and/or fluconazole: 400 mg PO BID; duration based on severity of disease and response
Newly approved formulation of Posaconazole
1-FDA has approved a new formulation of posaconazole (Noxafil, Merck), The agency approved posaconazole 100-mg delayed- release tablets, given as a loading dose of 300 mg (three 100-mg delayed- release tablets) twice daily on the first day, followed by a once- daily maintenance dose of 300 mg (three 100-mg delayed-release tablets) on the second day of therapy. Merck also markets posaconazole (also as Noxafil) in a 40 mg/mL oral suspension, which is dosed 3 times daily. Posaconazole delayed-release tablets and oral suspension are indicated for the prophylaxis of invasive Aspergillus andCandida infections in patients aged 13 years and older who are at high risk of developing these infections because of being severely immunocompromised Newly approved formulation of Posaconazole
2-FDA has approved an intravenous (IV) formulation of the posaconazole (Noxafil, Merck), according to the company. Posaconazole injection is indicated in patient at least 18 years of age, whereas the delayed-release tablets and oral suspension are indicated in patients aged 13 years and older. Posaconazole is indicated for prophylaxis of invasive Aspergillus and Candida infections in patient who are at high risk of developing these infections because of being severely immunocompromised, such as hematopoietic stem cell transplant recipients with graft-vs-host disease or those with hematologic malignancies with prolonged neutropenia from chemotherapy. 6-Clotrimazole (Canestin) Indication For fungal skin infection, vaginal candidiasis and otitis externa
Dose 1-vaginal cream: a- 1 %: insert 1 applicatorfulvaginal cream at bedtime for 7 consecutive days b- 2 %: insert 1 applicatorfulvaginal cream at bedtime for 3 consecutive days 2-topical cream and solution: apply to affected area twice daily for 7 consecutive days
a-Vaginal 2% cream : once daily , before sleep for 7days.
b-100 mg vaginal suppository once daily , before sleep for 7days .
c- 200 mg vaginal suppository once daily , before sleep for 3 day
Polyene Antifungals Polyene Antifungal It binds to sterols in fungal cell membrane, leading to alterations in cell permeability and cell death
1-Amphotericin B - It is most effective antifungal agents in the treatment of systemic fungal infection, especially in immunocompromised patients
Type Advantage Disadvantage Conventional cheap Toxic and side effects common Lipid formulation Less toxic and side effects Given when conventional thearapy contraindicated because of toxicity especially nephrotoxicity or when respone inadequate Expensive - Types 1-Amphotericin B
1-Amphotericin B
Precaution
1-infusion-related reaction: fever, chills, vomiting, nausea, headache, hypotension, dyspnea, tachypnea (need test dose before start Infusion) " A test dose is advisable before the first infusion, the patient should be observed for at least 30 min after the test dose " Premedication with acetaminophen, diphenhydramine,hydrocortisone should be used for patient who have previously experienced acute adverse reaction
1-Amphotericin B 2- Nephrotoxicity: need dose adjustment or drug D/C or change to liposomal form
3-electrolyte abnormalities : Hypokalemia, hypomagnesemia, and hypocalcemia
2-Nystatin( Mycostat) 2-nystatin Indication and Dose 1-Cutaneous or mucocutaneous Candida infections: apply 2-3 times daily for 2 weeks
2-vaginal infections: I tab daily at bedtime for 2 weeks
3- GI candidal infection:
a- oropharngeal candidiasis : Oral suspension: 400,000-600,000 units PO q6hr; swish in mouth several minutes and then swallow
Nystatin
b-Intestinal candidiasis -Oral tablets: 500,000-1,000,000 units q8hr -Powder: 1/8 to 1/4 teaspoonful in 1/2 cup of water (500,000-1,000,000 units) PO q8hr
Flucytosine Flucytocin
M.O.A It penetrates fungal cells and converted to fluorouracil, then incorporated to the RNA of fungal cell. This action leads to defect protein synthesis
Indications -Used alone not recommended -It is used with amphotericin B in synergistic combination for treatment of severe systemic fungal infection ( meningitis, septicemia, endocarditis, etc)
Black Box Warnings Use extreme caution in patients with renal impairment Monitor hematologic, renal, and hepatic function Review instructions thoroughly before administration
Griseofulvin
Griseofulfin M.O.A -It inhibits fungal cell activity by interfering with mitotic spindle structure - it deposit in keratin precursor cells and is tightly bound to new keratin, and this increases resistance to fungal invasion -It is mechanism of action similar to colchicines ( it may used for gout treatment
Griseofulvin Indication Treatment of susceptible tinea infections of skin,body,hair and nails
Duration of treatment Dependent on infection site 1-Tinea corporis: 2-4 weeks
2-Tinea capitis: 4-6 weeks; may be up to 8-12 weeks 3-Tinea pedis: 4-8 weeks
"Absorption increased with fatty meals"
Griseofulvin Most common Side effects - Headache, lethargy, syncope, confusion, lethargy, impaired performance, and skin rash
Severe skin reactions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis) and erythema multiforme reported, some resulting in hospitalization or death; discontinue if severe skin reaction occurs
Griseofulvin Drugs interaction 1-it increases the metabolism of warfarin and lead to decrease prothrombin time
2-Oral contraceptive may increase amenorrhea or increase breakthrough bleeding
-They cause cell wall lysis -have activity againt candida spp and aspergillus species -available as Injection dosage form
Synthetic allylamine M.O.A Inhibits squalene monooxygenase and this lead to interruption of fungal sterol biosynthesis
1- Terbinafine ( Lamisil )
Oral systemic preparation Indication and dose 1-Onychomycosis 250 mg (1 tablet) PO daily for 6 weeks (fingernail) or 12 weeks (toenail) Terbinafine ( Lamisil ) 2- Tinea pedis ( off-label use ) 250 mg/day PO for 2- 6 weeks 3- Tinea corporis and tinea crusis 250 mg/day PO for 2-4 weeks
Common side effects 1-headache 2-taste disturbances 3-visual disturbances 4-skin rash
Terbinafine ( Lamisil ) Topical preparation
Indication and dose 1- Tinea Pedis Apply to affected area BID until significant clinical improvement (no more than 4 weeks)
2-Tinea corporis and cruris Apply daily for 1 week (no more than 4 weeks)
Terbinafine cutaneous solution ( Lamisil once)
Indication It is a single dose treatment for tinea pedis
Side effect burning, dryness, pruritis, rash, irritation
Terbinafine cutaneous solution ( Lamisil once) - How to use: apply to both feet, even if signs are visible only on one foot. When applied to the feet, the medication dries quickly to a colourless film. The drug delivers into the skin where it lasts for a number of days to kill the fungus .after applying the drug, patient must not wash or splash feet for 24 hours
Naftifine ( Exodril) 2-Naftifine ( Exodril) Indication & Dose 1- 1% cream treatment -Used for treatmen of tinea pedis, tinea cruris, and tinea corporis -apply BID to the affected areas plus a 0.5-inch margin of healthy surrounding skin for 4 weeks Naftifine ( Exodril) 2- 2% cream or gel -Used for treatment of interdigital tinea pedis, tinea cruris, and tinea corporis -Apply daily to the affected areas plus a 0.5-inch margin of healthy surrounding skin for 2 weeks
Caution Avoid use of occlusive dressings
Amorolfine ( Loceryl)
Amorolfine
Indication Topical treatment of nail infections caused by fungi (onychomycosis)
Dose Apply to affected toenails or fingernails once or twice weekly
Ciclopirox ( Mycoster) Ciclopirox M.O.A Synthetic benzylamine It inhibits intermediary in synthesis of ergosterol, an essential component of fungal cell membranes Indication and dose 1-Mild to moderate onychomycosis of fingernails & toenails: 1- topical solution: apply over entire nail plate daily before sleep or 8 hours before washing to all affected nails
Ciclopirox ( Mycoster) 2-Tinea pedis, Tinea corporis, Tinea cruris, Tinea vesicolor, and cutaneous candidiasis : Cream and suspension: apply BID; gently massage into affected areas; if no improvement after 4 weeks re-evaluate diagnosis 3-Seborrheic dermatitis: -Gel: Apply BID; gently massage into affected areas; if no improvement after 4 weeks re- evaluate diagnosis
Tolnaftate Tolnaftate M.O.A distort the hyphae and stunt mycelial growth in susceptible fungi Indication & Dose Superficial fungal infection apply BID for 2-3 weeks
Clioquinol
Clioquinol It is used for fungal skin infection : apply two to four times a day up to 4 weeks
Newly approved drugs: 1-Luliconazole ( Luzu) - FDA has approved the azole antifungal luliconazole 1% cream to treat fungal infections
- Luliconazole 1% cream is indicated for the topical treatment of interdigital tinea pedis (athlete's foot), tinea cruris and tinea corporis , in adults aged 18 years and older.
1-Luliconazole ( Luzu) It is the first topical azole antifungal agent approved to treat tinea cruris and tinea corporis with a 1-week, once-daily treatment regimen. All other currently approved treatments require 2 weeks of treatment. For interdigital tinea pedis, the treatment period is 2 weeks, once daily 2- Efinaconazole Efinaconazole - It is used for the topical treatment of onychomycosis.
- Efinaconazole is an inhibitor of sterol 14- demethylase and is more effective in vitro than terbinafine, itraconazole, ciclopirox and amorolfine against dermatophytes, yeasts and non- dermatophyte molds.
- The mean mycological cure rate for efinaconazole is
similar to the oral antifungal itraconazole and exceeds the efficacy of topical ciclopirox - efinaconazole 10% nail solution is an effective topical monotherapy for distal and lateral subungual onychomycosis (<65% nail involvement, excluding the matrix) that shows further potential use as an adjunct to oral and device-based therapies. 2- Efinaconazole Pregnancy category and breast feeding Breast feeding Pregnancy category Drug Enters breast milk C Ketoconazole use caution as topical, vaginal not known C Miconazole Not recommended C Fluconazole Enter breast milk so weigh risk against benefits C Itraconazole not known if excreted in breast milk, weigh risk/benefit D Voriconazole unknown; weigh risk/benefit C Posaconazole Pregnancy category and breast feeding Breast feeding Pregnancy Drug use with caution B Clotrimazole -Conventional: contraindicated -liposomal: not recommended B Amphotericin B 1-systemicNot known if excreted in breast milk; use caution 2-Topical: no studies 3-vaginal: Poorly distributed in breast milk 1-systemic: c 2-topical: B 3-vaginal:A Nystatin not recommended c Flucytocin Avoid use X Griseofulvin Avoid use B terbinafine Pregnancy category and breast feeding Breast feeding Pregnancy Drug avoid unless potential benefit outweigh risk avoid unless potential benefit outweigh risk Amorolfin not known if distributed in breast milk B Ciclopirox Use caution B Naftifine Unknown C Tolnaftate