Abstract
Invasive mycoses are life-threatening opportunistic infections and have emerged as a major cause of morbidity and mortality in critically ill patients. This review focuses on recent advances in our understanding of the epidemiology, diagnosis and management of invasive candidiasis, which is the predominant fungal infection in the intensive care unit setting. Candida spp. are the fourth most common cause of bloodstream infections in the USA, but they are a much less common cause of bloodstream infections in Europe. About one-third of episodes of candidaemia occur in the intensive care unit. Until recently, Candida albicans was by far the predominant species, causing up to two-thirds of all cases of invasive candidiasis. However, a shift toward non-albicans Candida spp., such as C. glabrata and C. krusei, with reduced susceptibility to commonly used antifungal agents, was recently observed. Unfortunately, risk factors and clinical manifestations of candidiasis are not specific, and conventional culture methods such as blood culture systems lack sensitivity. Recent studies have shown that detection of circulating β-glucan, mannan and antimannan antibodies may contribute to diagnosis of invasive candidiasis. Early initiation of appropriate antifungal therapy is essential for reducing the morbidity and mortality of invasive fungal infections. For decades, amphotericin B deoxycholate has been the standard therapy, but it is often poorly tolerated and associated with infusion-related acute reactions and nephrotoxicity. Azoles such as fluconazole and itraconazole provided the first treatment alternatives to amphotericin B for candidiasis. In recent years, several new antifungal agents have become available, offering additional therapeutic options for the management of Candida infections. These include lipid formulations of amphotericin B, new azoles (voriconazole and posaconazole) and echinocandins (caspofungin, micafungin and anidulafungin).
Highlights
Fungi have emerged worldwide as an increasingly frequent cause of opportunistic infections
Described in immunocompromised hosts, primarily cancer patients, opportunistic fungal pathogens have been recognized as a frequent cause of infection in surgical and critically ill patients
Invasive candidiasis is recognized as a leading cause of morbidity and mortality in both immunocompetent and immunocompromised critically ill patients, with reported crude and attributable mortality rates of more than 40% to 60% and 20% to 40%, respectively [13,23,24,25,26,27,28,29]
Summary
Fungi have emerged worldwide as an increasingly frequent cause of opportunistic infections. Innate (C. krusei) or emerging (especially C. glabrata and C. guilliermondi) resistance to azoles among non-albicans Candida spp. has been noted in various regions of the world [16,17], which may limit the use of fluconazole as empirical therapy for yeast bloodstream infections in critically ill patients before species identification and results of antifungal susceptibility testing are known. Open-label, comparative multicentre, noninferiority trial conducted in patients with invasive Candida infections [33], voriconazole (6 mg/kg per day after a 12 mg/kg loading dose on day 1) was shown to be at least as effective as and safer than amphotericin B deoxycholate (0.7 to 1 mg/kg per day) followed by intravenous or oral fluconazole (400 mg/day). Other articles in the series can be found online at http://ccforum.com/articles/
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