Bench-to-bedside review: Candida infections in the intensive care unit

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 beta-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).

Figure 1

Mortality rates associated with Candida infections. Shown are rates of all-cause mortality from candidaemia or invasive candidiasis at (a) the end of antifungal therapy and (b) the end of follow up in recent randomized clinical trials. Numbers given in parenthesis on the x-axis indicate the reference numbers of the clinical trials. Duration of follow-up in panel a: ¹2 weeks, ²2 to 4 weeks and ³2 to 3 weeks. Duration of follow-up in panel b: ¹8 to 10 weeks and ²12 to 14 weeks. AmB-d, amphotericin B-deoxycholate; Anidula, anidulafungin; Caspo, caspofungin; Flu, fluconazole; L-AmB, amphotericin B, liposomal preparation; Mica, micafungin; Vori, voriconazole.