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INTRODUCTION

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Candida species are yeast forms that are ubiquitous in nature and frequent colonizers of human skin and mucous membranes of the gastrointestinal, respiratory, and female genital tracts. Candida species are the most common cause of human fungal infections, although they rarely cause invasive disease in the absence of mucosal barrier disruption or compromised immune systems. Only a small number of the more than 150 species of Candida that have been described are considered to be pathogenic. There are at least 15 Candida species associated with human disease, but most invasive infections are due to 5 pathogens: C albicans, C glabrata, C tropicalis, C parapsilosis, and C krusei. Historically, C albicans has accounted for the majority of invasive infections, but in more recent reports, non-albicans species have been isolated in half or more of the cases. In addition, the incidence of infections due to C albicans isolates that are resistant to azole antifungals is increasing. This changing epidemiology has implications for appropriate treatment of antifungal-resistant Candida infections.

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PATHOGENESIS AND EPIDEMIOLOGY

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Candida species are part of the normal human flora of the skin and mucous membranes. The incidence of colonization with Candida species depends on host characteristics such as age and overall health. Neonates are frequently colonized with Candida species, and localized oropharyngeal candidiasis (thrush) is not uncommon in this population. Hospitalized and ill children are more frequently colonized than are healthy children. Candida species have relatively low virulence factors compared to other organisms and, therefore, rarely cause disease in the normal host. For candidiasis to occur, the host must have impaired resistance to disease, the number of yeast organisms must be high, or both.

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Neonates and pregnant women have impaired host resistance to Candida species, as do patients with immunodeficiencies (congenital or acquired), induced immunosuppression (due to chemotherapy or corticosteroids), or debilitation (secondary to trauma or surgery). Advances in health care that have decreased mortality for preterm newborns and oncology patients have been associated also with changes in host defense and normal flora, which have in turn led to a larger population at risk for invasive Candida infection. These at-risk populations frequently receive multiple and long-term courses of medications, particularly antimicrobials (altering the normal flora), and have defects in mucosal or skin barriers (such as chemotherapy-induced mucositis or the presence of indwelling intravascular catheters), which puts them at high risk for development of candidiasis.

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Invasive candidiasis includes candidemia and deep-seated infection. Deep-seated infection usually results from candidemia but may occur through direct inoculation (eg, leaky surgical anastomosis leading to peritonitis). Candidemia is frequently due to translocation of Candida species in the gut into the bloodstream. In patients with indwelling central venous catheters, Candida species introduced to the bloodstream from the gut or skin colonize the catheter and form a biofilm, which will then persistently release Candida into the bloodstream. Candidemia may lead to secondary ...

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