1 What is the definition of disseminated fungal infection?

We define disseminated fungal infection as the presence of a fungal pathogen in the blood (fungemia) and/or any other sterile deep-seated structure because of hematogenous seeding. This distinguishes disseminated infection from superficial infection, which mostly involves the mucocutaneous structures, that is, dermatitis, onychitis, stomatitis, esophagitis, and keratitis, as well as from simple colonization, which is the isolation of a fungal pathogen from a nonsterile site without any sign of infection attributable to the specific pathogen. Invasive fungal infection is a more general term and refers to fungemia and other fungal infections such as disseminated candidiasis, endocarditis, meningitis, and hepatosplenic infection.

2 What are the most clinically important fungal pathogens?

Candida spp., Aspergillus spp., and Cryptococcus spp. are by far the most common fungal pathogens encountered in the hospital setting, with Candida being the leading fungal pathogen. Of note is that Aspergillus spp. have been steadily increasing in the intensive care unit (ICU) setting.

3 What is the epidemiology of fungal infections in hospitalized patients?

In the last 25 years the total number of fungal infections in hospitalized patients has increased from 6% in 1980 to 10.4% in 1990 and currently may be as high as 25%. Candida species are the fourth most commonly recovered blood culture isolates in the United States.

4 Why has the incidence of fungal infection increased so dramatically?

Fungi generally do not cause invasive infection in healthy individuals. Robust cellular and antibody-mediated immunity and intact mucosal barriers play a major role in shielding the human body from opportunists such as Candida spp., which seek a way of passing through tissues and entering the bloodstream and other deep-seated organs. With the numbers of immunosuppressed patients increasing through cancer and chemotherapy, transplantation, and HIV infection, as well as with the increased use of vascular and urinary catheters and broad-spectrum antibacterial agents, an alarming increase of deep-seated fungal infections has been seen in clinical practice.

5 What fungi are responsible for invasive infection in humans?

C. albicans accounts for the majority (mostly > 50%-60%) of all Candida infections, but this percentage is declining to 45%. C. tropicalis, C. glabrata, and C. krusei account for most of the remainder. This is particularly important because certain Candida spp. such as C. krusei can be resistant to fluconazole. On the other hand, Aspergillus spp. account for at least 15% to 20% of all fungal infections; however, the rate can be higher in patients after lung transplantation. Other less-common but increasing mycoses include blastomycoses, coccidioidomycoses, cryptococcosis, histoplasmosis, and sporotrichosis.

6 What are the most important risk factors for disseminated Candida infection?

7 List the diagnostic criteria for disseminated fungal infection

Definitive:

Suggestive: three confirmed colonized sites (should be regarded as a risk factor rather than a definite sign of infection)

8 How reliable are these diagnostic criteria?

The preceding criteria are positive in only 30% to 50% of patients with disseminated fungal infection. Therefore a high index of suspicion must be maintained.

9 Should asymptomatic candiduria be treated?

Among low-risk individuals no treatment is recommended. Amphotericin bladder irrigation is no longer recommended. Usually a change of urinary catheter should suffice. Among high-risk patients (patients with neutropenia or with urologic manipulations, low-birth-weight infants) treatment is similar to the one used for invasive candidiasis.

10 Should a central venous catheter be removed once candidemia is confirmed?

Practice guidelines indicate that all central venous catheters should be removed once candidemia is confirmed (Table 35-1). Of note is that a recent randomized controlled trial and other studies question the benefit of early removal of central venous catheters in the onset of candidemia for some selected patients. We recommend following the standard practice guidelines.

^{Table 35-1} Recommendation on CVC Removal in Patients with Candidemia

Modified from www.guidelines.gov and Mermel LA, Allon M, Bouza E, et al: Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America [published errata appear in: Clin Infect Dis 50:457, 2010, and Clin Infect Dis 50:1079, 2010]. Clin Infect Dis 49:1-45, 2009.