Invasive fungal infections: the challenge continues

Invasive fungal infections (IFIs) are being increasingly recognized as a major threat in critically ill adult and paediatric patients. They can range widely in severity and can be life threatening in some patients. Candida and Aspergillus species are the most common causes of IFIs, but other yeasts and filamentous fungi are emerging pathogens. C. albicans, the most significant pathogenic species, is seen in almost all of the 17% of patients treated in the intensive care unit (ICU) who develop IFIs, and is associated with significant morbidity and mortality. Non-albicans spp. are becoming more common, particularly in neutropenic patients and those on existing azole therapy. Early diagnosis is challenging due to delays in, and low sensitivity of, confirmatory blood cultures, and difficulty in discriminating colonization from invasive candidiasis. Once diagnosed, early initiation of appropriate antifungal therapy is essential for reducing morbidity and mortality. Amphotericin B deoxycholate and azoles, once standard therapy, have been largely superseded in the ICU by broad-spectrum azoles, liposomal amphotericin B and the newer echinocandin agents with improved efficacy/tolerability profiles. The echinocandins (caspofungin, micafungin and anidulafungin) exhibit fungicidal activity against Candida spp. and fungistatic activity against Aspergillus spp. Echinocandins have demonstrated clinical efficacy, broad spectrum of activity and favourable pharmacological properties, and are, therefore, likely to replace fluconazole as the initial antifungal agent of choice among critically ill patients. Current evidence supports echinocandin empirical therapy for candidaemia or invasive candidiasis in ICU patients with or without neutropenia, and as rescue therapy in patients with life-threatening IFIs caused by strains resistant to other antifungals. Anidulafungin represents a new advance in the treatment of IFIs and is approved for treatment of candidaemia, intra-abdominal abscesses, peritonitis and oesophageal candidiasis.