Systemic fungal infections

The incidence of systemic fungal infections has increased over the last two decades. Two new antifungal agents have been recently licensed. Voriconazole is a broad-spectrum triazole available in intravenous and oral preparations. In treatment of invasive aspergillosis, it was associated with higher survival at 12 weeks, and fewer drug-related adverse events compared with starting therapy with amphotericin B deoxycholate. Caspofungin is the first of a new class of intravenous antifungals (echinocandins) that target glucan synthesis in the fungal cell wall. It is active against Candida and Aspergillus, and is as effective as and associated with fewer adverse events than amphotericin B in treatment of invasive candidiasis. Management of invasive candidiasis and aspergillosis is discussed in the light of these new agents and advances in susceptibility testing for Candida and diagnostic tests for aspergillosis. Cryptococcal meningitis remains a leading cause of death in HIV-infected patients in Africa and Asia. Treatment is with amphotericin B plus flucytosine for 2 weeks, followed by fluconazole. Patients with high CSF opening pressure may need serial lumbar puncture to prevent sequelae such as visual impairment. Mucormycosis is a rare, devastating infection in diabetic and neutropenic patients. Rhinocerebral infection presents with orbital swelling, fever and facial pain; pulmonary infection may resemble aspergillosis. Diagnosis is by visualization of broad, irregular hyphae with right-angle branching in tissue samples. Management is debridement and high-dose liposomal amphotericin. Endemic dimorphic fungal infections include histoplasmosis, which is widespread but most common in the Ohio and Mississippi valleys, and penicilliosis in South East Asia.