can be life-threatening; cryptococcal meningitis is the most
common form of fungal meningitis. The treatment of choice
in cryptococcal meningitis is amphotericin by intravenous
infusion andflucytosine by intravenous infusion for^2 weeks,
followed byfluconazole by mouth for 8 weeks or until
cultures are negative. In cryptococcosis,fluconazole is
sometimes given alone as an alternative in HIV-positive
patients with mild, localised infections or in those who
cannot tolerate amphotericin. Following successful
treatment,fluconazole can be used for prophylaxis against
relapse until immunity recovers.
Histoplasmosis
Histoplasmosis is rare in temperate climates; it can be life-
threatening, particularly in HIV-infected persons.
Itraconazole can be used for the treatment of
immunocompetent patients with indolent non-meningeal
infection, including chronic pulmonary histoplasmosis.
Amphotericin by intravenous infusion is used for the initial
treatment of fulminant or severe infections, followed by a
course of itraconazole by mouth. Following successful
treatment, itraconazole can be used for prophylaxis against
relapse until immunity recovers.
Skin and nail infections
Mild localised fungal infections of the skin (including tinea
corporis, tinea cruris, and tinea pedis) respond to topical
therapy. Systemic therapy is appropriate if topical therapy
fails, if many areas are affected, or if the site of infection is
difficult to treat such as in infections of the nails
(onychomycosis) and of the scalp (tinea capitis).
Oral imidazole or triazole antifungals (particularly
itraconazole) and terbinafine p. 726 are used more
frequently than griseofulvin p. 379 because they have a
broader spectrum of activity and require a shorter duration
of treatment.
Tinea capitisis treated systemically; additional topical
application of an antifungal may reduce transmission.
Griseofulvin is used for tinea capitis in adults and children; it
is effective against infections caused byTrichophyton
tonsuransandMicrosporumspp. Terbinafine is used for tinea
capitis caused byT. tonsurans[unlicensed indication]. The
role of terbinafine in the management ofMicrosporum
infections is uncertain. Fluconazole or itraconazole are
alternatives in the treatment of tinea capitis caused byT.
tonsuransorMicrosporumspp. [both unlicensed indications].
Pityriasis versicolormay be treated with itraconazole by
mouth if topical therapy is ineffective;fluconazole by mouth
is an alternative. Oral terbinafine isnoteffective for
pityriasis versicolor.
Antifungal treatment may not be necessary in
asymptomatic patients with tinea infection of the nails. If
treatment is necessary, a systemic antifungal is more
effective than topical therapy. Terbinafine and itraconazole
have largely replaced griseofulvin for the systemic treatment
ofonychomycosis, particularly of the toenail; they should be
used under specialist advice in children. Although
terbinafine is not licensed for use in children, it is considered
to be the drug of choice for onychomycosis. Itraconazole can
be administered as intermittent‘pulse’therapy. Topical
antifungals also have a role in the treatment of
onychomycosis.
Immunocompromised children
Immunocompromised children are at particular risk of
fungal infections and may receive antifungal drugs
prophylactically; oral triazole antifungals are the drugs of
choice for prophylaxis. Fluconazole is more reliably absorbed
than itraconazole, butfluconazole is not effective against
Aspergillusspp. Itraconazole is preferred in patients at risk of
invasive aspergillosis. Micafungin p. 372 can be used for
prophylaxis of candidiasis in patients undergoing
haematopoietic stem cell transplantation whenfluconazole
or itraconazole cannot be used.
Amphotericin by intravenous infusion or caspofungin is used
for the empiricaltreatmentof serious fungal infections in
immunocompromised children; caspofungin is not effective
against fungal infections of the CNS.Triazole antifungals
Triazole antifungal drugs have a role in the prevention and
systemic treatment of fungal infections.
Fluconazole is very well absorbed after oral
administration. It also achieves good penetration into the
cerebrospinalfluid to treat fungal meningitis. Fluconazole is
excreted largely unchanged in the urine and can be used to
treat candiduria.
Itraconazole is active against a wide range of
dermatophytes. There is limited information available on
use in children. Itraconazole capsules require an acid
environment in the stomach for optimal absorption.
Itraconazole has been associated with liver damage and
should be avoided or used with caution in patients with liver
disease;fluconazole is less frequently associated with
hepatotoxicity.
Voriconazole is a broad-spectrum antifungal drug which is
licensed in adults for use in life-threatening infections.Imidazole antifungals
The imidazole antifungals include clotrimazole p. 515 ,
econazole nitrate p. 515 , ketoconazole p. 444 , and
tioconazole p. 726. They are used for the local treatment of
vaginal candidiasis and for dermatophyte infections.
Miconazole p. 516 can be 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.Polyene antifungals
The polyene antifungals include amphotericin and nystatin
p. 710 ; neither drug is absorbed when given by mouth.
Nystatin is used for oral, oropharyngeal, and perioral
infections by local application in the mouth. Nystatin is also
used forCandida albicansinfection of the skin.
Amphotericin p. 373 by intravenous infusion is used for
the treatment of systemic fungal infections and is active
against most fungi and yeasts. It is highly protein bound and
penetrates poorly into bodyfluids and tissues. When given
parenterally amphotericin is toxic and side-effects are
common. Lipid formulations of amphotericin (Abelcet®and
AmBisome®) are significantly less toxic and are
recommended when the conventional formulation of
amphotericin is contra-indicated because of toxicity,
especially nephrotoxicity or when response to conventional
amphotericin is inadequate; lipid formulations are more
expensive.Echinocandin antifungals
The echinocandin antifungals include caspofungin p. 372
and micafungin p. 372. They are only active against
Aspergillusspp. andCandidaspp.; however, micafungin is
not used for the treatment of aspergillosis. Echinocandins
are not effective against fungal infections of the CNS.
Echinocandin antifungals have a role in the prevention and
systemic treatment of fungal infections.Other antifungals
Flucytosine p. 378 is used with amphotericin 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 toflucytosine can develop during therapy and
sensitivity testing is essential before and during treatment.
Flucytosine has a role in the treatment of systemic
candidiasis and cryptococcal meningitis.BNFC 2018 – 2019 Fungal infection 371
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