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Overview of Systemic Fungal Infections

Overview of Systemic Fungal Infections

ABSTRACT: A steady increase in the frequency of invasive fungal infections has been observed in the past 2 decades, particularly in immunosuppressed patients. In recipients of bone marrow transplants, Candida albicans and Aspergillus fumigatus remain the primary pathogens. In many centers, however, Candida species other than C albicans now predominate, and many cases of aspergillosis are due to species other than A fumigatus. Additionally, heretofore unrecognized and/or uncommon fungal pathogens are beginning to emerge, including Blastoschizomyces capitatus, Fusarium species, Malassezia furfur, and Trichosporon beigelii. These opportunistic fungal pathogens are associated with various localized and disseminated clinical syndromes, and with substantial morbidity and mortality. These established, invasive mycoses, particularly in bone marrow transplant recipients, are the focus of this discussion. [ONCOLOGY 15(Suppl 9):11-14, 2001]

The frequency of invasive fungal infections continues
to increase, both in the general population and in immunosuppressed patients
(bone marrow transplant [BMT] recipients, patients with severe and prolonged
neutropenia). Several factors are responsible for this increase in fungal
infections, including increasing numbers of patients with impaired host defenses
due to underlying diseases and/or immunosuppressive therapy. The inability to
diagnose many invasive fungal infections in a timely manner continues to be a
significant problem, and improved diagnostic methods are needed to permit early
detection of infection. Despite the availability of several newer antifungal
agents, therapy remains suboptimal, and much work remains to be done in defining
the roles of established and novel modalities for treatment and prevention of
infection.

Risk Factors and Frequency of Infection

Several risk factors account for the increased frequency of invasive fungal
infections (Table 1). Moreover, multiple risk factors may be present in the same
patient, which further increases risk. The most important risk factor for the
development of fungal infection, particularly in patients with hematologic
malignancies (with or without BMT), is severe and prolonged neutropenia. Chronic
graft-vs-host disease, immunosuppressive therapy, multiple courses of
broad-spectrum antibiotic therapy, the presence of vascular access catheters,
parenteral nutrition, colonization at multiple sites, and prolonged stay in an
intensive care unit are all associated with an increased frequency of invasive
fungal infection. Finally, environmental exposure (hospital construction sites,
contaminated cooling/heating systems) may also be a significant contributory
factor. Prevention strategies, therefore, include the use of rooms equipped with
high-efficiency particulate air (HEPA) filters to reduce the risk of
environmental exposure.[1,2]

Data from the National Nosocomial Infections Surveillance (NNIS) system have
best documented the changing epidemiology of nosocomial infections in US
hospitals.[3] These data demonstrate that the rate of nosocomial fungal
infections ranges from 2.0 to 3.8 infections per 1,000 hospital discharges from
1980 to 1990, with the proportion of fungal blood stream infections among all
nosocomial bloodstream infections increasing from 5.4% to 9.9%.

The most marked increases occurred in surgical services (124%) and medical
services (73%), and the rate of nosocomial candidemia increased by approximately
500% in large teaching hospitals, and by 219% and 370% in small teaching
hospitals and large nonteaching hospitals, respectively. It is of interest to
note that the recently reported Surveillance and Control of Pathogens of
Epidemiological Importance (SCOPE) data from 49 US hospitals indicate that
Candida
bloodstream infections were nearly as common in the general hospital
wards (43%) as in the intensive care unit (ICU) (57%).[4] In this survey,
Candida
species were the fourth most common bloodstream pathogen, accounting for
7.6% of infections, with such infections being associated with a crude mortality
rate of 40%.

Spectrum of Infection

The most common yeast infection in the BMT setting (and in other neutropenic
patients) is candidiasis. Prior to the use of fluconazole prophylaxis, the
incidence of invasive candidal infection was between 10% and 20%, and the most
common species was C albicans.[5] This has decreased substantially since
fluconazole (Diflucan), and more recently itraconazole (Sporanox), has been used
for prophylaxis. Many studies have documented the changing epidemiology of
Candida
infections with decreasing isolation rates for C albicans, and
increasing isolation rates for other Candida species.[6,7]

In a study of 491 episodes of hematogenous candidiasis from the University of
Texas M. D. Anderson Cancer Center, 42% of cases were caused by C albicans, 18%
by C tropicalis, 17% by C parapsilosis, 11% by C glabrata, and the rest by other

Candida
species. Wide use of fluconazole appeared to be playing a major role in
this observed shift. However, a more recent survey from the same institution of
the distribution of Candida species in pediatric patients with candidemia
revealed the same pattern (Table 2).[7,8] These patients do not receive
fluconazole prophylaxis, are housed in a separate unit, and are cared for by
staff dedicated to the pediatric unit. While antifungal prophylaxis—particularly
with fluconazole—and nosocomial transmission have contributed to the changing
epidemiology of infection, these data emphasize that other factors may also be
involved.

Similarly, although A fumigatus has been the primary Aspergillus species, A
terreus
and other Aspergillus species appear to be increasing in frequency.
Other less common molds, including Fusarium species, the Zygomycetes, Bipolaris
and other dematiaceous fungi, and the yeast Trichosporon beigelii are being
encountered with increasing frequency. The endemic mycoses (histoplasmosis,
blastomycosis, cryptococcosis, coccidioidosis, etc) are seen sporadically in
immunocompromised patients.

Characteristics of Candida Infection

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