Predisposing Factors for Oral Candidiasis

• Xerostomia
• Antibiotic Therapy
• Poor Oral or Denture Hygiene
• Malnutrition
• Acidic Saliva
• Heavy Smoking
• Blood Dyscrasias

Immunological Factors

• Old Age/Infancy
• Radiation/Chemo
• AIDS

Endocrine Abnormalities

• Diabetes
• Hypothyroidism
• Corticosteroid Therapy

Uncomplicated localized infection in patients with normal immune function.

Medication should be continued for 48 hrs after clinical signs disappear.

Disseminated or multi-focal disease

Immunocompromised patients

Class:  Polyene

Dosage Form:  Topical

 Site of Action:  Cell Membrane

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Drug of choice for fungal infections of the oral cavity.

Broad spectrum of activity (Candida, Histoplasmosis, Cryptococcus).

Used prophylactically in immunocompromised patients.

Not absorbed from the skin or mucosal membranes (GI Tract).

Too toxic for parenteral use; only used topically.

Dosage Forms:

• Oral Suspension 100,000 u/mL -- Rinse mouth with 5 mL for at least 2 minutes qid (4x/day) pc (after meals) and hs (at bedtime), then swallow; NPO 30 minutes after use
• Lozenges 200,000 units -- dissolve completely in mouth (do not chew or swallow whole) 5 times per day; NPO 30 minutes after use
• Both treatments usually last 14 days
• Patients say it has a bitter, foul taste

Class:  Polyene

Dosage Form:  Topical, IV

Site of Action:  Cell Membrane

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Dosage Forms:

• Topical - Oral Suspension 100 mg/mL -- Rinse mouth for at least 2-3 minutes qid pc and hs then swallow; NPO 30 minutes after use

• IV - Binds to cholesterol in plasma membranes; most toxic antibiotic in current use; given over a period of 2-6 hrs; Adverse Effects:  hypotension, delirium, fever, nausea, vomiting, abdominal pain, anorexia, headache, nephrotoxicity; AKA "amphoterrible"

Class:  Imidazole

Dosage Form:  Topical

Site of Action:  Cell Membrane

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Nitrogen atoms of the azole ring bind to lanosterol 14-α-demethylase.

The conversion of lanosterol to ergosterol is inhibited.

Ergosterol is part of the cell membrane.

Only used topically because it is not absorbed from the GI tract.

Drug of choice for oral candidiasis in patients with AIDS.

Binds to the oral mucosa, gradually released, fugistatic concentrations for several hours.

Dosage Forms:

• Clotrimazole Troches 10 mg -- Dissolved completely in mouth (do not chew or swallow whole) 5 times per day; NPO 30 minutes after use
• Patients report that it tastes better than nystatin

Class:  Imidazole

Dosage Form:  Topical, PO

Site of Action:  Cell Membrane

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Nitrogen atoms of the azole ring bind to lanosterol 14-α-demethylase.

The conversion of lanosterol to ergosterol is inhibited.

Ergosterol is part of the cell membrane.

Dosage Forms:

• Tablets 200 mg -- 1 tab PO qd with orange juice or a meal for 14 days
• Topical Cream 2%
• Well absorbed from the GI tract in conditions of low pH.  Drug interations with drugs that increase the pH of the stomach.

Adverse Effects:  hepatoxicity (0.01%).

Inhibits synthesis of testosterone and estradiol.

Inhibitor of Cytochrome p450 3A4 (metabolizes Cyclosporin, Phenytoin, Sulfonylureas, Warfarin).

Seldom used.

Class:  Triazole

Dosage Form:  IV, PO

Site of Action:  Cell Membrane

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A triazole derivative:  more selective inhibitor of fungal cell membrane p450.

Adverse Effects:  GI upset, less hepatoxicity than ketoconazole.

Weak inhibitor of Cytochrome p450 3A4.

Dosage Forms:

• Tablet 100 mg -- 2 tabs PO stat, then 1 tab PO qd for 13 days (14 days total)
• Oral Suspension 50 mg/5 mL --Rinse mouth with 20 mL on day 1 for 1 minute then swallow.  Repeat with 10 mL qd for 13 days (14 days total)

Resistance to Fluconzaole:

• Prolonged use
• Decreased susceptibility (correlate with treatment failure in HIV positive patients)
• Fluconazole resistant fungi are cross resistant to other azole antifungal agents

Class:  Triazole

Dosage Form:  IV, PO

Site of Action:  Cell Membrane

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Triazole, mechanism like fluconazole.

 Significant inhibitor of p450 3A4.

Used if infection is resistant to nystatin, ketoconazole, fluconazole.

Resistance in Candida species isolated from patients on prolonged therapy.

Dosage Forms:

• Capsules 100 mg -- take 1 capsule PO bid.
• Suspension 10 mg/mL -- rinse mouth with 20 mL for 1 minute qd then swallow and continue for 14 days.

Class:  Hydroxyquinoline

Dosage Form:  Topical 

• Halogenated hydroxyquinoline with amebicidal, antitrichomonal, antibacterial, and antifungal activity.
• Chelates trace metals at bacterial surfaces that are essential for growth.
• Indicators:  angular cheilitis

Dosage Forms:

• 1% topical cream with 1% hydrocortisone -- apply to affected areas after each meal and hs

Griseofulvin:  ringworm infections of the scalp, skin, and nails (site of action = cell membrane)

Flucytosine and amphotericin:  systemic candidiasis and cryptococcosis (site of action = nucleic acid synthesis)

• Clotrimazole Lozenges 10 mg
• Nystatin Lozenges 200,000 units -- Dissolve slowly in mouth (do not chew or swallow whole) 5 times per day; NPO 30 minutes after use
• Fluconazole tablets 150 mg --Take 1 tablet PO stat

• Fluconazole Oral Suspension 50 mg/5 mL
• Itraconazole Oral Suspension 10 mg/mL -- Rinse mouth with 20 mL for 1 minute then swallow qd and continue for 14 days
• Fluconazole tablets 100 mg -- Take 2 tablets PO stat, then 1 tablet PO qd for 13 days (14 days total)

• Nystatin Cream 100,000 u/g
• Clotriamazole Cream 1%
• Ketoconazole Cream 2%
• Apply thin coat of medicine to entire inner surface of denture after each meal for 14 days.

More denture treatments:

• Full strength bleach (only for dentures without metal) -- soak for 10 minutes once a week then rinse well
• Anti-fungal Vaginal tablets -- dissolve tablet in water, soak denture for 10 minutes