Antifungal Chemotherapy
Antifungal Chemotherapy
Polyenes
Amphotericin B
Amphotericin B remains the mainstay of therapy for systemic mycoses against which all other parenteral antifungals are measured to assess efficacy. Side effects with conventional amphotericin B are common and include chills, fever, vomiting, pain, nephrotoxicity and anaemia. Daily doses range from 0.3 - 1.0 mg/kg/day given over 1 - 4 hours as an infusion in 5% dextrose.
Nystatin
This polyene does not have the patient compliance, potency or extended antifungal spectrum of the azoles, but remains an alternative for vaginal yeast infection during pregnancy. It is only available for topical application.
Natamycin
It is the therapy of choice for keratitis due to filamentous fungi. It is only available for topical application.
Azoles
Most of the imidazoles available in South Africa are topical agents and have few side
effects. Those available in South Africa include:
• Clotrimazole
• Miconazole
• Econazole
• Tioconazole
• Intravenous miconazole is obsolete except for the treatment of Pseudoallescheria boydii infection.
Oral ketoconazole has potential hepatotoxicity and endocrine effects and is poorly absorbed in the absence of gastric acidity.
The triazoles, fluconazole and itraconazole, appear to be less hepatotoxic, do not affect cortisol and testosterone synthesis, and have fewer drug interactions than ketoconazole.These agents have significant activity against a broad spectrum of fungal pathogens causing infection in humans.
Fluconazole is water soluble and can be used IV as well as orally. It penetrates the CSFm and is excreted in an active form in urine.
Terbinafine
This expensive antifungal can be given orally for the treatment of tinea (ringworm) involving the hands, feet and nails (preferred to griseofulvin).
Side effects are uncommon (gastrointestinal and skin reactions).
The optimal clinical effect may be observed some weeks after completion of therapy.
A topical preparation is also available for cutaneous infections. This is effective against pityriasis versicolor whereas the oral formulation is not.
Amorolfine
This topical compound has been used with reasonable success in the treatment of onychomycosis. Although it is not as effective as terbinafine, it has excellent patient compliance, tolerability and safety.
Griseofulvin
Griseofulvin at 10 mg/kg/daily with foods to a maximum of 1 g daily in 3 divided doses continued for 12 to 18 months, has in the past been used for difficult dermatophyte infections involving the hair shaft, feet and nails.
Potential teratogenicity and other adverse effects (eg. reduction in effectiveness of oral contraceptives, photosensitivity, neurological problems) and the availability of other drugs now limit its use.
Flucytosine
Flucytosine is seldom used alone because of the risk of emergence of resistance during monotherapy. It is usually combined with amphotericin B to treat invasive candida and cryptococcus infections. It is not readily available in South Africa.
The usual dose is 100 - 150 mg/kg/day in 4 divided doses.
Treatment of Specific Fungal Infections
Aspergillosis
Treatment is reserved for invasive pulmonary or disseminated infection, although recent data indicates a role for itraconazole in allergic bronchopulmonary aspergillosis.
High dose amphotericin B (at least 0.7 mg/kg/day) for 6 weeks or more. Itraconazole at 400 - 600 mg/day for 6 months is a possible alternative. Involved tissue may require surgical removal.
Candidiasis
Oral/vaginal: Topical clotrimazole, econazole, miconazole or tioconazole. Patient tolerance and compliance in vaginal infection is better with shorter courses of oral therapy (e.g. single oral dose 150 mg fluconazole).
During pregnancy: Only topical azole therapies (clotrimazole, miconazole, tiocona-
zole or terconazole) should be used to treat pregnant women. Topical nystatin is an
alternative.
Chronic/recurrent mucocutaneous: Fluconazole 400 mg daily for 2 days followed by
100 - 200 mg daily for 3 weeks.
Cystitis: Oral fluconazole 150 mg daily for 7 days OR 200 - 300 ml of amphotericin B
solution, 5 - 10 mg/l (25 - 50 mg in 500 ml of 5% dextrose water), instilled by triple lumen
catheter with cross-clamping for 60 - 90 minutes, twice daily for 2 days.
Candidaemia in post- surgical patients or infected vascular lines:
Remove infected lines.
Amphotericin B 0.7 - 1.0 mg/kg/day for 7 - 10 days or fluconazole orally at a dose of 400 mg per day for 14 days or more.
Invasive or systemic: Amphotericin B 0.7 - 1.0 mg/kg/day.
Fluconazole, in doses of 400mg/day IV, is an alternative treatment to amphotericin B in non-neutropenic patients.
Corneal infection (keratomycosis):
Topical natamycin suspension (2.5%) 2 hourly or
more frequently initially.
Cryptococcus infections
Amphotericin B 0.7 mg/mg IV for 2 weeks followed by fluconazole 400 mg PO daily for an additional 8 weeks is the recommended regimen for cryptococcal meningitis.
The addition of flucytosine (not available in South Africa) in doses of 100 mg/kg/day in conjunction with the amphotericin B phase of treatment, does not dramatically improve immediate outcome.
Initial therapy with fluconazole (400 - 800 mg PO) is
associated with a 50% relapse rate; this regimen may be considered in patients with
very mild disease and those who present with cryptococcosis without meningeal involvement.
In HIV-infected patients, fluconazole in doses of 200 - 400 mg PO daily should be prescibed as maintenance therapy.
Dermatophyte infections (Ringworm or Tinea)
Topical imidazoles for uncomplicated ringworm of the body or groin twice daily for at least 10 days after clearance of lesions. Alternatives include terbinafine (1% cream twice daily), amorolfine (0.25% cream once daily). For infection involving scalp or beard, oral itraconazole (100 mg once daily for 2 - 4 weeks) or terbinafine (250 mg/day for 3 - 6 weeks) together with a topical imidazole. Chronic hand/foot lesions, including nails, require oral itraconazole (6 months) or terbinafine (6 weeks to 3 months) or possibly 5% amorolfine nail lacquer (twice daily for 6 - 12 months).
Pityriasis versicolor
A single oral dose of 400 mg ketoconazole or two weeks of topical treatment with an
imidazole.
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