Epidemiology Fungal Infections

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Epidemiology

Incidence and Impact of Fungal Infections in the Compromised Host

Accurate data regarding the incidence of systemic mycoses and

associated mortality are difficult to obtain. Reporting requirements

for fungal infections vary considerably in the United States and

elsewhere. In addition, many deaths due to mycoses are not reported

because they are undiagnosed, misdiagnosed, or not specified because

they occur secondary to a preexisting condition. Nevertheless, many

indications suggest that the incidence of fungal infections and

attributable mortality are rising. This reflects the increasing

number of susceptible hosts due to factors such as the human

immunodeficiency virus (HIV) epidemic, advances in organ

transplantation and cancer chemotherapy, and the increasing use of

invasive procedures for treatment, monitoring, and life support

[Joklik et al., 1992; Rees et al., 1998].

The following is a presentation of data from several surveillance

studies documenting the increasing incidence of both nosocomial and

community-acquired fungal infections and the consequent rise in both

mortality and prolonged hospitalizations. Most notable is the sharp

increase in bloodstream infections due to Candida species and the

growing importance of previously uncommon fungal pathogens,

including non-albicans species of Candida.

Incidence of Invasive Mycoses in a General Population

The incidence of fungal infections is not uniform throughout the

world. Most mycoses are caused by fungi that reside in nature, but

their distribution varies considerably. Thus, the attack rates and

incidence of specific mycoses can vary widely. The following

discussion highlights data from a study of the epidemiology of

invasive mycoses among residents of the San Francisco Bay Area of

California. The population of this area is characterized by a high

prevalence of HIV infection, which has an impact on the incidence of

fungal infections [Rees et al., 1998].

Rees et al. [1998] examined data regarding the clinical diagnosis

and laboratory documentation of fungal infections from 45 San

Francisco Bay Area hospitals during 1992 and 1993. During the study

period, over 1600 patients who met the case definition for fungal

disease were identified. Most patients (>90%) had serious underlying

medical conditions. The most common were HIV infection (47.4%),

cancer (14.7%), diabetes mellitus (9.9%), and chronic lung disease

(9.3%). In 1048 patients (65%), the episode of fungal infection was

their first. Based on this number, the annual incidence of invasive

mycoses in this population was calculated as 178.3 per million of

the population studied per year. Overall, the mortality rate for

first-episode infections in this population exceeded 22%.

The incidence and fatality rates of several specific mycoses were

also examined. Candida species accounted for most infections,

followed by Cryptococcus, Coccidioides, Aspergillus, and Histoplasma

[Rees et al., 1998].

To examine trends in rates of invasive mycoses (e.g.,

histoplasmosis, coccidioidomycosis, aspergillosis, cryptococcosis,

candidiasis, sporotrichosis, and blastomycosis) over specific time

periods, Rees et al. [1998] compared their data with previous

estimates based on large databases of hospital discharge diagnoses

maintained by the U.S. Commission on Professional and Hospital

Activities (CPHA). Taking into account differences in methodology

and populations between the studies, the investigators noted marked

increases in the rates of candidiasis and cryptococcosis, as well as

aspergillosis.

Trends in Nosocomial Fungal Infections

Consistent with their role as opportunists, fungi have become

important nosocomial pathogens. Usually, patients develop hospital

infections due to their own increased susceptibility to infection or

the procedures performed in the hospital. Nosocomial infections are

significant because they contribute to excess length and cost of

hospitalization. When severe, they also increase the risk of patient

mortality [Mims et al., 1998].

Overall, bacteria account for most nosocomial infections. During the

past 20 years, however, increases in the severity of illness of

hospitalized patients, the use of invasive medical devices, and the

administration of more potent broad-spectrum antibiotics have

resulted in an increase in the incidence of infections due to fungi.

Most notable is the sharp rise in the rate of bloodstream infections

with Candida and the increasing importance of uncommon fungal

pathogens such as non-albicans species of Candida, Fusarium species,

Trichosporon species, and dematiaceous fungi [Jarvis, 1995; Mims et

al., 1998; Pfaller, 1995].

In the United States, the Centers for Disease Control and Prevention

(CDC) collected data on the epidemiology of nosocomial infections

for over 20 years via the National Nosocomial Infections

Surveillance System (NNIS). The following figure documents the

increase in the incidence of fungal infections at 115 NNIS hospitals

from 1980-1990. During this period, 30,477 fungal infections were

reported, and the rate of fungal infections nearly doubled,

increasing from 2.0 to 3.8 per 1000 patients discharged. Overall,

the proportion of nosocomial infections due to fungal pathogens at

NNIS hospitals rose from 6.0% in 1980 to 10.4% in 1990 [beck-Sague

et al., 1993].

Nosocomial Fungal Infection Rates at NNIS Hospitals, 1980-1990

From Beck-Sague et al. [1993]; with permission.

Click on image for larger version.

Rising rates of fungal infections were reported in each of the major

departments of the NNIS hospitals. The largest increases occurred in

the medicine and surgery services, which reported increases of 73%

and 124%, respectively (see figure below). From January 1986 to

December 1990, the highest rates of fungal infections were noted in

the burn/trauma, cardiac surgery, oncology, high-risk nursery, and

general surgery services [beck-Sague et al., 1993].

Nosocomial Fungal Infection (NFI) Rates in Surgery, Medicine, and

Newborn Nursery Services: NNIS Data, 1980-1990

From Beck-Sague et al. [1993]; with permission.

Click on image for larger version.

Sites most commonly affected in nosocomial infections are surgical

wounds, the urinary tract, the respiratory tract, and the

bloodstream. The 1980s witnessed an increase in the frequency of

fungal infections at each of these sites (see figure below). The

most dramatic increase occurred in the incidence of fungemias, which

rose by 400% from January 1980 to April 1990. Similar trends have

been reported in Europe [beck-Sague et al., 1993; et al.,

1997; Jarvis, 1995].

Percentage Increase in Rates of Nosocomial Fungal Infections by Site

or Type of Infection: NNIS Data, 1980-1990

Adapted from Jarvis [1995]; with permission.

Click on image for larger version.

The following figure shows the overall distribution of fungi causing

infections at NNIS hospitals from January 1980 to 1990. Candida

albicans was the predominant pathogen accounting for 59.7% of fungal

isolates, followed by other Candida species (25.9%) and Aspergillus

species (1.3%). Aspergillus was the pathogen reported for many

fungal pneumonias [beck-Sague et al., 1993; Mandell et al., 1995].

Distribution of Nosocomial Fungal Pathogens: NNIS Data, 1980-1990

Data from Beck-Sague et al. [1993].

Click on image for larger version.

Overall, Candida ranks among the most common nosocomial pathogens. A

review of NNIS data from 1986-1990 showed Candida to be the sixth

most common pathogen hospital-wide and the fourth most frequent

pathogen in intensive care units (ICUs), where it accounted for 25%

of all urinary tract infections. Candida also emerged as a leading

cause of nosocomial bloodstream infections [Jarvis, 1995].

Fungemia due to Candida

Estimates are that among the 35 million patients admitted to

hospitals in the United States each year, at least 2.5 million will

develop nosocomial infections. Almost 250,000 of these will be

bloodstream infections, which contribute significantly to excess

length and cost of hospital stay and patient mortality. The

attributable mortality from bloodstream infections averages 26% but

varies according to the specific organism involved [Pittet et al.,

1994; Pittet and Wenzel, 1995].

The incidence of bloodstream infections and the risk of death is

highest in critically ill patients, especially those admitted to the

surgical intensive care unit (SICU). In one study, bloodstream

infection was associated with a doubling of SICU stay and an excess

length of hospital stay of 24 days in survivors. Extra costs

attributed to the infection averaged $40,000 per survivor [Pittet et

al., 1994].

Information from a variety of sources highlights the increasing

importance of Candida as a bloodstream pathogen.

Data collected by the NNIS showed that between 1980 and 1989 the

incidence of nosocomial candidemia increased by almost 500% in large

teaching hospitals and by 219% and 370% in small teaching hospitals

and large nonteaching hospitals, respectively [banerjee et al.,

1991].

The Surveillance and Control of Pathogens of Epidemiological

Importance (SCOPE) Program identified Candida species as the fourth

leading cause of nosocomial bloodstream infections, accounting for

almost 8% of all infections in 49 surveyed medical centers

throughout the United States from 1995 to 1998. In this study, 57%

of Candida infections occurred in ICUs. Of all the pathogens

isolated, Candida had the highest attributable mortality rate (40%)

[Edmond et al., 1999].

Pittet et al. [1997] demonstrated a higher mortality rate with

Candida compared with nonfungal bloodstream pathogens. These

investigators analyzed data from 1745 episodes of bloodstream

infections at a single U.S. hospital between 1986 and 1991 to

evaluate the effect of microbiological factors on patient outcome.

Candida was the only microorganism identified as an independent

determinant of the risk of death. Candida species accounted for 6.5%

of isolates (the fourth most commonly isolated pathogen) and were

associated with the highest attributable mortality rates (35% at 28

days and 69% at discharge).

Populations at risk

In general, the incidence of candidemia and other nosocomial fungal

infections is greater in high-risk ICUs than in other parts of the

hospital. Individuals in the ICU include the most sick and severely

injured patients in the hospital. These patients often include the

youngest and oldest patients; they are subjected to the most

invasive procedures for diagnosis, therapy, monitoring, and life-

support; they are given more antibiotics; and they often stay in the

hospital longer. Each of these factors individually is recognized as

increasing the risk of infection, especially with opportunistic

pathogens [Pfaller, 1995; Wenzel, 1995; et al., 1997].

By the nature of their underlying conditions and the procedures used

in their management, several patient populations are recognized as

being at high risk for hospital-acquired infections due to fungi,

primarily Candida [Pfaller, 1994; Jarvis, 1995; Wenzel, 1995]. Among

these are:

patients being treated for cancer, particularly hematologic

malignancies

recipients of organ and bone marrow transplants

high-risk newborns in the neonatal ICU

patients in the SICU, especially those who have undergone cardiac

surgery or major abdominal surgery and who have complicated

postoperative courses

patients with severe trauma or burns.

References

Banerjee SN, Emori TG, Culver DH, et al. Secular trends in

nosocomial primary bloodstream infections in the United States, 1980-

1989. National Nosocomial Infections Surveillance System. Am J Med.

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Beck-Sague C, Jarvis WR, and the National Nosocomial Infections

Surveillance System. Secular trends in the epidemiology of

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Edmond MB, Wallace SE, McClish DK, et al. Nosocomial bloodstream

infections in United States hospitals: a three-year analysis. Clin

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JE Jr, Bodey GP, Bowden RA, et al. International Conference

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