Occurrence, Presentation and Treatment of Candidemia

Małgorzata Mikulska; Valerio Del Bono; Sandra Ratto; Claudio Viscoli

Disclosures

Expert Rev Clin Immunol. 2012;8(8):755-765. 

In This Article

Abstract and Introduction

Abstract

Candida is one of the most common causes of nosocomial bloodstream infections. Candidemia is not confined to hematological patients, intensive care units or abdominal surgery wards, but it is remarkably frequent in the internal medicine setting. High mortality associated with candidemia can be reduced by prompt, appropriate antifungal therapy. The epidemiology of species has been shifting toward non-albicans strains. Significant improvements in nonculture-based diagnostic methods, such as serological markers, have been made in recent years, and novel diagnostic techniques should be further studied to enable early pre-emptive therapy. Treatment guidelines indicate that echinocandins are at present the best choice for patients who are severely ill or possibly infected with fluconazole-resistant strains.

Introduction

Candida is a yeast responsible for most of the systemic invasive fungal infections in humans. The incidence of systemic Candida infections, particularly nosocomial bloodstream infections (candidemia), has increased significantly in recent years,[1] being the fourth most common pathogen isolated in blood cultures in the USA.[2] In Europe, it ranks among the ten most frequently isolated pathogens[3,4] and in a recent survey of intensive care units (ICUs) worldwide, the prevalence of candidemia was found to be 6.9 per 1000 patients.[5] While general incidence of candidemia has increased, possibly due to a rising number of patients with comorbidities and risk factors for invasive candidiasis (IC), settings such as ICU or stem cell transplant units have experienced a decrease in candidemia after introducing fluconazole prophylaxis.[6–8]

Candidemia is a life-threatening infection with high morbidity and mortality.[9,10] Although most commonly reported around 30–40%, crude mortality rates might be as high as 50–60%.[5,11–14] However, attributable mortality may be substantially lower, ranging from 10 to 49%, depending on the definition used.[15–17]

Until not long ago, Candida albicans accounted for the majority of infections. Nowadays, non-albicans species, which can be resistant to fluconazole (Candida krusei and Candida glabrata), are being more and more frequently isolated.[14] Immunocompromised patients, such as those affected by solid tumors or hematological malignancies, are at the highest risk for developing candidemia, whereas other well-known risk groups include ICU patients, low birthweight neonates or patients undergoing repeated intestinal surgery. More recently, a patients population characterized by multiple comorbidities, such as older age, need for parental nutrition or bacterial infections, is increasingly being described as being at risk of systemic candidiasis. Indeed, recent reports show that more than 50% of all candidemia episodes occur in this patient population, usually hospitalized in internal medicine wards.[14,18]

The diagnosis of candidemia is not straightforward, as clinical signs and symptoms are aspecific, and, due to a low diagnostic yield of traditional blood cultures (still the gold standard for diagnosis), a significant percentage of candidemias go undetected. The use of antifungal prophylaxis further hampers diagnostic sensitivity, while predisposing patients to infections due to fungi with intrinsic or acquired resistance to some antifungals. Moreover, antifungals are not free of interactions and toxicities. Mortality rate in cases of IC, particularly candidemia, remains high but can be decreased by appropriate and timely antifungal therapy.[19–22] Thus, a prompt identification of patients with possible candidemia, for example, by clinical prediction rules, positive serological markers or suggestive clinical presentation, is mandatory. Fortunately, the clinical conditions that predispose patients to fungal infections are being better understood and new noninvasive diagnostic methods, such as high-quality radiological imaging and serologic markers (e.g., 1,3 β-d-glucan testing) are increasingly available. Last but not the least, new effective and less toxic antifungal drugs, in particular echinocandins, are being increasingly used and numerous international guidelines have been developed in order to help clinicians in the correct management of this infection. Epidemiology, risk factors, diagnosis and management of candidemia will be discussed further.

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