Surveillance of Antimicrobial Studies
National Surveillance of Nosocomial Blood Stream Infection Due to Species of Candida Other than Candida albicans: Frequency of Occurrence and Antifungal Susceptibility in the SCOPE Program

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Abstract

A national surveillance program of nosocomial blood stream infections (BSI) in the USA between April 1995 and June 1996 revealed that Candida was the fourth leading cause of nosocomial BSI, accounting for 8% of all infections. Forty-eight percent of 379 episodes of candidemia were due to species other than Candida albicans. The rank order of non-C. albicans species was C. glabrata (20%) > C. tropicalis (11%) > C. parapsilosis (8%) > C. krusei (5%) > other Candida spp. (4%). The species distribution varied according to geographic region, with non-C. albicans species predominating in the Northeast (54%) and Southeast (53%) regions, and C. albicans predominating in the Northwest (60%) and Southwest (70%) regions. In vitro susceptibility studies demonstrated that 95% of non-C. albicans isolates were susceptible to 5-fluorocytosine, and 84% and 75% were susceptible to fluconazole and itraconazole, respectively. Geographic variation in susceptibility to itraconazole, but not other agents, was observed. Isolates from the Northwest and Southeast regions were more frequently resistant to itraconazole (29–30%) than those from the Northeast and Southwest regions (17–18%). Molecular epidemiologic studies revealed possible nosocomial transmission (five medical centers). Continued surveillance for the presence of non-C. albicans species among hospitalized patients is recommended.

Introduction

During the 1980s, the frequency of nosocomial candidemia increased dramatically. Candida was noted to be the fourth most common cause of nosocomial blood stream infection (BSI), accounting for approximately 8% of all hospital-acquired BSI among medical centers surveyed by the Centers for Disease Control (CDC) (Banerjee et al 1991; Emori and Gaynes 1993; Schaberg et al 1991). It was noted at that time that approximately one-third of Candida BSI were due to species other than C. albicans (Banerjee et al 1991). Since 1990, it has become clear that Candida spp. remain an important cause of nosocomial BSI, and that the proportion of BSI due to species of Candida other than C. albicans may be increasing (Fridkin and Jarvis 1996; Pfaller 1996). A review of the literature from 1952 to 1992 by Wingard (1995)failed to support the notion that over time a greater proportion of candidal infections were caused by species other than C. albicans. However, the most recent surveys have observed 40% to 50% of candidal BSI to be caused by species of Candida other than C. albicans (Nguyen et al 1996; Pfaller 1996; Rex et al 1995; Wingard 1995). Studies by Price et al (1994), Nguyen et al (1996), and Abi-Said et al (1997)confirm these data.

One explanation for the emergence of species of Candida other than C. albicans is the selection of less susceptible species by the pressure of antifungal agent use (Pfaller 1995a; Price et al 1994; Wingard et al 1991, Wingard et al 1993). Species-specific differences in susceptibility to fluconazole and other antifungal agents clearly exist (Pfaller and Barry 1995; Pfaller et al 1997; Price et al 1994; Wingard et al 1991, Wingard et al 1993) and may account for the emergence of non-albicans species in some institutions. The approximate rank order of susceptibility of Candida species to the triazole antifungal agents is C. albicans (most susceptible) > C. tropicalis > C. parapsilosis > C. glabrata > C. krusei (least susceptible) (Pfaller and Barry 1995; Pfaller et al 1997; Price et al 1994; Rex et al 1995). Recently Abi-Said et al (1997)reported that BSI due to C. krusei and C. glabrata were significantly more likely to occur in patients who had received fluconazole during hospitalization, whereas infections due to C. albicans and C. tropicalis were more likely among patients who had not received that agent. Infections due to C. parapsilosis were more likely to be related to the presence of an intravascular catheter and were not influenced by exposure to fluconazole or other antifungal agents (Abi-Said et al 1997). In considering these findings, it is important to note the observation of Wingard (1995)that the frequency of candidiasis due to non-albicans species varies widely among different institutions (range 14–100%) and may be influenced by multiple factors, including patient population, antimicrobial usage, cytotoxic chemotherapy, and underlying diseases, as well as antifungal therapy.

The above data support the need for accurate identification of Candida BSI isolates to species level. In addition, there is a need for ongoing surveillance of antifungal susceptibility patterns as important components of a program designed to prevent and control nosocomial fungal infections (Graybill 1997; Pfaller 1995a, Pfaller 1996; Pfaller et al 1997). Although antifungal susceptibility testing has only recently been standardized (National Committee for Clinical Laboratory Standards (NCCLS) (National Committee for Clinical Laboratory Standards 1997; Pfaller et al 1997), the development of microdilution methods (Pfaller and Barry 1995; Pfaller et al 1997) and interpretive breakpoints for fluconazole and itraconazole (National Committee for Clinical Laboratory Standards 1997; Rex et al 1997) facilitate the use of this technology in a nosocomial infection surveillance program (Pfaller et al 1997).

In this nosocomial BSI surveillance study conducted from 1995 to 1996 as part of the SCOPE (Surveillance and Control of Pathogens of Epidemiologic Importance) Surveillance Program, we describe the frequency of occurrence and antifungal susceptibility profile of species of Candida other than C. albicans. The frequency of resistance to the triazole antifungal agents (fluconazole, itraconazole) and observations on the molecular epidemiology of non-albicans BSI isolates is also described.

Section snippets

Study Design

The SCOPE Program was established to measure the predominant pathogens and antimicrobial susceptibility patterns of nosocomial BSI isolates from approximately 50 medical centers throughout the USA (Voelker 1996). Participants were selected to represent medical institutions of various sizes (range 60–1200 beds) from a broad range of geographic regions. Approximately equal numbers of participants were included in each of four geographic regions (Northeast [NE], Southeast [SE], Northwest [NW],

Frequency of Occurrence of Blood Stream Pathogens

During the 14-month study period (April 1995 to June 1996), a total of 4,725 BSI were reported by SCOPE participants. Table 1 lists the 10 most frequently isolated pathogens causing nosocomial BSI in these hospitals. These 10 organism groups accounted for 94.9% of all nosocomial BSI during this time period. Candida species were the fourth most common blood stream pathogen (379 infections), accounting for 8.0% of all BSI. Among the 379 BSI due to Candida spp., 183 (48%) were due to species other

Discussion

The results from the SCOPE Program confirm the previous observations of the CDC and document the prominent role of Candida species as etiologic agents of nosocomial BSI (Banerjee et al 1991; Emori and Gaynes 1993; Fridkin and Jarvis 1996). Furthermore, our findings support the more recent reports of Nguyen et al (1996)and of Abi-Said et al (1997)indicating an increasing role of non-C. albicans species as causes of nosocomial BSI. Importantly, we provide further documentation of the emergence of

Acknowledgements

We thank Kay Meyer for secretarial assistance in the preparation of the manuscript. This study was partially supported by grants from Wyeth-Ayerst (Pearl River, NJ) and Pfizer, Inc. (New York, NY). We acknowledge the excellent cooperation and participation of all member institutions of the SCOPE Program. Participants contributing data/isolates to the present study include: Chandler Hospital, Savannah, GA (A. Davis, L. Formby), St. Joseph Hospital, Omaha, NE (S. Cavalieri, A. Lorenzen), St. Jude

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