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Fungi cause a wide range of diseases, ranging from cutaneous
dermatophyte infections to invasive infection in the severely
immunocompromised patient. They may have a yeast-like morphology
(see below), or be filamentous (see Filamentous fungi
are widely distributed in the environment. They form
part of the normal commensal population of the skin, gastrointestinal
tract and female genital tract. Following the use of broadspectrum
antibacterial agents, fungal overgrowth may develop
into infection. Patients with immunodeficiencies are particularly
susceptible to this progression. Most infections are caused by
Candida albicans. Infection with other species such as C. tropicalis,
C. parapsilosis, C. glabrata and C. pseudotropicalis are a problem
in immunocompromised patients because they may be resistant to
the antifungal agents used in therapy or prophylaxis.
Although these organisms possess melanin, adhesins and extracellular
lipases and proteinases, they have only modest capacity to
invade. Infection occurs when the natural resistance provided by
the normal bacterial flora is altered by antibiotics, or where there
is a severe loss of immune function.
cause pain and itching with creamy curd-like plaques
on mucosal surfaces that bleed when removed. Skin and nail-bed
infections are common. In immunocompromised patients, pharyngitis
and oesophagitis can be severe; the associated dysphagia
may lead to weight loss and is an AIDS-defining illness. Systemic
invasion is common in neutropenic patients. Candida spp.
also cause systemic and line-associated infection following broadspectrum
antimicrobial therapy in intensive care patients.
Diagnosis is by microscopy, culture or nucleic acid amplification test
(NAAT). The significance of each isolate is determined in relation
to the overall clinical picture. Species identification is by biochemical
testing or increasingly by sequencing the 18S rRNA gene.
are susceptible to amphotericin, with the exception
of C. lusitaniae. They are usually susceptible to the imidazoles (e.g.
fluconazole) and to 5-flucytosine.
Cryptococcus neoformans is a saprophyte and animal commensal;
the composition of pigeon faeces favours its growth. It is a rare
cause of chronic lymphocytic meningitis in patients with lymphoma,
those taking steroid or cytotoxic therapy and those with
intense exposure, such as pigeon fanciers. Cryptococcus is an
important pathogen in patients with T-cell deficiency.
The pathogenicity depends on an antiphagocytic capsule, melanin
production and several lytic enzymes.
Infection usually presents as subacute meningitis, although pneumonia
and fungaemic shock are recognized. In patients with
AIDS, relapses are common and lifelong suppressive therapy is
Infection is diagnosed by microscopy in CSF using Gram stain or
India ink, or by detection of the capsular polysaccharide antigen
by latex-agglutination. It can be cultured and identified by biochemical
tests or 18S rRNA sequencing.
Liposomal amphotericin is the treatment of choice and flucytosine
and fluconazole may also be used.
Malassezia furfur infects the stratum corneum, causing brown,
scaly macules. Patients with AIDS may develop severe dermatitis.
Topical application of antifungal agents is usually successful.
Systemic yeast infections
Five main species of yeast are associated with systemic
infection: Histoplasma capsulatum, H. capsulatum var. duboisii,
Blastomyces dermatitidis, Coccidioides immitis and Paracoccidioides
These organisms have a defined geographical distribution:
south-west USA, South America and Africa. Infection is acquired
by the respiratory route. Severe disease is more likely in patients
with reduced cell-mediated immunity.
Although usually asymptomatic or self-limiting, pulmonary or
cutaneous infection may disseminate in infants or immunocompromised
patients, causing severe illness.
These infections are diagnosed by microscopy and culture of
blood, sputum, CSF, urine or pus. The organisms are hazardous
and should be handled in a specialized containment facility.
Patients with severe disease may be treated with amphotericin B.
The azole group of compounds (clotrimazole, miconazole, fluconazole
and itraconazole) act by blocking the action of cytochrome
P450 and sterol 14α-demethylase. This latter enzyme allows the
incorporation of 14-methyl sterols into the fungal membrane,
instead of ergosterol. Resistance can develop during long-term
Clotrimazole and miconazole are frequently used as topical
preparations for minor infections.
Fluconazole can be given orally, topically and parenterally. It is
widely distributed, crosses the blood-brain barrier and is active
against Candida and Cryptococcus but not against filamentous
fungi. It is used for the prophylaxis and treatment of cryptococcal
infections and treatment of superficial and systemic candidiasis.
Although well tolerated, it may cause liver enzyme abnormalities
and has significant drug interactions, increasing the serum concentration
of phenytoin, ciclosporin and oral hypoglycaemic agents
and reducing the rate of warfarin metabolism.
In addition to being effective against Candida spp., C. neoformans
and Histoplasma, itraconazole also displays activity against filamentous
fungi, including Aspergillus
and the dermatophytes. It is
indicated in the treatment of invasive candidiasis, cryptococcosis,
aspergillosis, superficial mycoses and pityriasis versicolor. Resistance
is rare. It is well absorbed and can be given orally, achieving
high tissue concentrations.
Voriconazole and posoconazole
Voriconazole is a broad-spectrum triazole that is active against
many yeasts and moulds including Aspergillus
. It has been reported
to have a better success rate in proven invasive Aspergillus
than amphotericin, but treatment is associated with transient
visual disturbance. Posoconazole has a wide spectrum of activity.
Further agents are in development.
This synthetic fluorinated pyrimidine inhibits Candida spp., C.
neoformans and some moulds. The drug disrupts protein synthesis.
It is well absorbed orally and can be given intravenously. Adverse
events include bone marrow suppression, thrombocytopenia and
abnormal liver function tests. Resistance develops rapidly with