Trends in species distribution and susceptibility to fluconazole among blood stream isolates of Candida species in the United States

Abstract

National surveillance of blood stream infections (BSI) attributable to Candida spp. has been limited to date. Recent studies have suggested an increase in the proportion of BSI attributable to non-Candida albicans species and have also raised concerns regarding the emergence of antifungal resistance among Candida spp. The increased utilization of broad-spectrum antifungal agents and the recognition of Candida spp. as prominent pathogens with the potential for developing antifungal resistance, emphasize the need for ongoing surveillance of antifungal susceptibility patterns. In this investigation trends in species distribution and susceptibility to fluconazole among BSI isolates of Candida spp. referred to our laboratory by United States hospitals were evaluated over the 7-year period from 1992 to 1998. A total of 1579 BSI isolates from more than 50 medical centers were processed. Overall, C. albicans accounted for 52% of isolates followed by C. glabrata (18%), C. parapsilosis (15%), C. tropicalis (11%), and C. krusei (2%). The proportion of BSI isolates that were C. albicans ranged from 45% in 1992 to 60% in 1998. Among the non-C. albicans isolates, C. glabrata succeeded C. parapsilosis as the most common species beginning in 1995. Overall, the susceptibility of all Candida species (C. albicans plus all other species) to fluconazole remained stable (MIC₉₀, 16 μg/mL). The fluconazole MIC₉₀ for C. albicans was 0.5–2.0 μg/ml for all years studied except 1995 (8.0 μg/mL) and was 1.0 μg/mL overall. The present study suggests a continued prominent role of C. albicans as a cause of BSI, and a constant level of susceptibility of Candida BSI isolates to fluconazole over 7 years. These data should serve as a baseline for future surveillance efforts for anti-fungal agents tested against yeast BSI isolates.

Introduction

There is an ever-increasing need to understand the epidemiology of both nosocomial and community-acquired mycoses Pfaller 1996, Pfaller 1998, Rees et al 1998. Recent studies have confirmed the predominant role of candidiasis among the invasive mycoses as we approach the year 2000 Abi-Said et al 1997, Fridkin and Jarvis 1996, Nguyen et al 1996, Pfaller et al 1998a, Pfaller et al 1998b, Pfaller et al 1998c, Pfaller et al 1998d, Rees et al 1998. Among the species of Candida causing blood stream infection (BSI) in the United States (US), Candida albicans accounts for 50% to 70% of all infections (Pfaller 1996). Concerns have been raised regarding the selection of non-albicans species and the development of azole resistance among C. albicans and other normally susceptible species due to the extensive use of fluconazole in both hospital and community settings Abi-Said et al 1997, Ghannoum et al 1996, Nguyen et al 1996, Powderly 1994, Price et al 1994, Rex et al 1995a, Wingard 1995. Although these issues are clearly important, it must be realized that the majority of studies addressing these concerns are limited to individual institutions or are limited in time Abi-Said et al 1997, Price et al 1994, Wingard et al 1991, Wingard et al 1993. Furthermore, in contrast to the literature concerning fluconazole-resistant C. albicans in AIDS patients with oropharyngeal candidiasis Ghannoum et al 1996, Pfaller et al 1994, Powderly 1994, Rex et al 1995a, Wardle et al 1995, there is little, if any, evidence for increased resistance to fluconazole among C. albicans BSI isolates (Boschman et al 1998, Pfaller et al 1998a-d; Rex et al. 1995b).

Studies by Wingard (1995) and by Pfaller et al. (1998a-d) point out the significant variation among institutions with respect to the frequency of C. albicans and other Candida species as etiologic agents of BSI. Furthermore, Pfaller et al. (1998a-d) suggests that susceptibility to fluconazole among C. albicans BSI isolates may also vary considerably from institution to institution or among geographic regions. Thus, it is not clear whether the overall pattern of species causing BSI in the US is changing and whether those species, particularly C. albicans, are becoming more resistant to fluconazole over the period of time since the introduction of this agent Pfaller 1996, Wingard 1995. Given the extensive use of fluconazole in many institutions, it is reasonable to take a longitudinal view of species distribution as well as fluconazole susceptibility among BSI isolates of Candida obtained from US medical centers. In the present study, we report the trends in species distribution and in vitro susceptibility to fluconazole observed among over 1500 BSI isolates of Candida spp. that were submitted from more than 50 US hospitals to the University of Iowa for antifungal susceptibility testing between 1992 and 1998.