42 Fungal infections
Fungi are ubiquitous microorganisms that differ from bacteria in their cellular structure, and this makes them naturally resistant to antibacterial agents (Table 42.1). Fungi are broadly divided into yeasts and moulds. Yeasts are typically round or oval shaped microscopically, grow flat round colonies on culture plates and reproduce by forming buds from their cells. Moulds (e.g. Aspergillus, Mucor) appear as a collection or mass (mycelium) of individual tubular structures called hyphae that grow by branching and longitudinal extension. They appear as a fuzzy growth on appropriate conducive medium (e.g. Penicillium colonies on stale bread or Sabourauds agar). The most commonly seen yeast, Candida, occasionally produces pseudohyphae.
Fungi | Bacteria |
---|---|
Eukaryotes | Prokaryotes, eubacteria |
Cell and cytoplasm | Cell and cytoplasm |
Nucleus with multiple chromosomes enclosed in a nuclear membrane | No nucleus or nuclear membrane, has single chromosome |
Contains endoplasmic reticulum, golgi apparatus, mitochondria and ribosomes | Other structures absent except ribosomes |
Cytoplasmic membrane | Cytoplasmic membrane |
Contains phospholipids and sterols | Contains phospholipids and no sterols |
Cell wall | Cell wall |
Contains chitins, mannans,+/- cellulose | Contains peptidoglycan, lipids and proteins |
There are hundreds of species of fungi found in the environment, but only the important human fungal pathogens and their treatment will be discussed in this chapter. The fungi of medical importance can be divided into four groups (Table 42.2).
Group | Examples | Infections caused |
---|---|---|
Yeast | Candida spp. | Oral and vaginal thrush |
Deep seated: candidaemia, empyema | ||
Cryptococcus neoformans | Meningitis | |
Saccharomyces cervesiae | Rare systemic infection in immunocompromised host | |
Malassezia furfur | ||
Yeast-like | Geotrichium candidium | |
Trichosporon beigelii | ||
Dimorphic fungi | Blastomyces dermatitidis | For first three: deep systemic organ involvement, more commonly in the immunocompromised host |
Coccidioides immitis | Deep subcutaneous infection following trauma | |
Histoplasma capsulatum | ||
Paracoccidioides brasiliensis | ||
Sporothrix schenckii | ||
Moulds | ||
1. Hyaline | ||
a. Zygomyces | Rhizopus | Infections in neutropenic patients and those with diabetic ketoacidosis |
Mucor | ||
Absidia | ||
b. Hyalohyphomycosis | Aspergillus fumigatus and other Aspergillus spp. | Systemic infection: invasive pulmonary or central nervous system involvement |
Fusarium | Fusarium keratitis | |
Scedosporium apiospermum | Deep infection in immunocompromised host, for example, transplant patients | |
2. Dermatophytes | Trichophyton spp. | For all three: various skin (ringworm) hair and nail infections |
Microsporum spp. | ||
Epidermophyton | ||
3. Dematiaceous | Alternaria spp. | Deep tissue infection with granulomas |
Cladophialora spp. | Chromomycosis, mycetomas |
Some fungi like Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis are known as dimorphic fungi (Table 42.2) because they are found in the infected host in yeast form at 35–37 °C temperature but grow as moulds, in vitro, at room temperatures (22 °C incubation).
Fungal infection
More often, fungi are a cause of superficial infections of the skin and mucous membranes.
Antifungal agents
Topical and systemic antifungal agents are available to treat mucocutaneous candidiasis, various forms of tinea (ringworm) and other dermatophytosis, onychomycosis and deep-seated systemic infections (e.g. candidaemia, mucor mycoses, fungal endocarditis, osteomyelitis). Some infective conditions and their treatment are dealt with in the sections that follow. The side effects of a range of antifungal agents are set out in Table 42.3.
Drug | Side effects |
---|---|
Griseofulvin | Mild: headache, gastro-intestinal side effects. Hypersensitivity reactions such as skin rashes, including photosensitivity |
Moderate: exacerbation of acute intermittent porphyria; rarely, precipitation of systemic lupus erythematosus. Contraindicated in both acute porphyria, systemic lupus erythematosus, pregnancy and severe liver disease | |
Terbinafine | Usually mild: nausea, abdominal pain; allergic skin reactions; loss and disturbance of sense of taste. Not recommended in patients with liver disease |
Amphotericin | Immediate reactions (during infusion) include headache, pyrexia, rigors, nausea, vomiting, hypotension; occasionally, there can be severe thrombophlebitis after the infusion |
Nephrotoxicity and hypokalaemia | |
Anaemia due to reduced erythropoiesis | |
Peripheral neuropathy (rare) | |
Cardiac failure (exacerbated by hypokalaemia due to nephrotoxicity) | |
Immunomodulation (the drug can both enhance and inhibit some immunological functions) | |
Flucytosine | Mild: gastro-intestinal side effects (nausea, vomiting). Occasional skin rashes Moderate: myelosuppression (dose related), hepatotoxicity |
Fluconazole | Mild: nausea, vomiting and occasional skin rashes; occasionally, elevated liver enzymes (reversible) |
Moderate or severe: rarely, hepatotoxicity and severe cutaneous reactions, especially in AIDS patients | |
Itraconazole | Mild: nausea and abdominal pain; occasional skin rashes |
Moderate or severe: rarely, hepatotoxicity | |
Voriconazole | Similar to fluconazole and itraconazole |
Mild: reversible visual disturbances occur in about 30% patients | |
Caspofungin | Mild: gastro-intestinal side effects; occasional skin rashes |
Superficial infection
Candida infections
Treatment
Systemic treatment
Three triazole agents: fluconazole, itraconazole and voriconazole are available for systemic treatment of oral and vulvo vaginal candidiasis (VVC). A good source of advice on treatment is that from the Infectious Diseases Society of America (Pappas et al., 2009):
Guidance on the treatment of topical and systemic therapy (Pappas et al., 2009) are also available for treatment of mild, moderate and severe oropharyngeal and oesophageal candidiasis and suppressive therapy for patients with HIV infection.