Epidemiology and Outcomes of Invasive Candidiasis Due to Non-albicans Species of Candida in 2,496 Patients: Data from the Prospective Antifungal Therapy (PATH) Registry 2004–2008 Michael A. Pfaller 1,2 *, David R. Andes 3 , Daniel J. Diekema 2 , David L. Horn 4 , Annette C. Reboli 5 , Coleman Rotstein 6 , Billy Franks 7 , Nkechi E. Azie 7 1 JMI Laboratories, North Liberty, Iowa, United States of America, 2 Department of Pathology, University of Iowa, Iowa City, Iowa, United States of America, 3 Department of Medicine, University of Wisconsin, Madison, Wisconsin, United States of America, 4 David Horn LLC, Doylestown, Pennsylvania, United States of America, 5 Department of Medicine, Cooper Medical School of Rowan University, Camden, New Jersey, United States of America, 6 Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Ontario, Canada, 7 Astellas Scientific and Medical Affairs, Northbrook, Illinois, United States of America Abstract This analysis describes the epidemiology and outcomes of invasive candidiasis caused by non-albicans species of Candida in patients enrolled in the Prospective Antifungal Therapy Alliance (PATH Alliance) registry from 2004 to 2008. A total of 2,496 patients with non-albicans species of Candida isolates were identified. The identified species were C. glabrata (46.4%), C. parapsilosis (24.7%), C. tropicalis (13.9%), C. krusei (5.5%), C. lusitaniae (1.6%), C. dubliniensis (1.5%) and C. guilliermondii (0.4%); 111 infections involved two or more species of Candida (4.4%). Non-albicans species accounted for more than 50% of all cases of invasive candidiasis in 15 of the 24 sites (62.5%) that contributed more than one case to the survey. Among solid organ transplant recipients, patients with non-transplant surgery, and patients with solid tumors, the most prevalent non- albicans species was C. glabrata at 63.7%, 48.0%, and 53.8%, respectively. In 1,883 patients receiving antifungal therapy on day 3, fluconazole (30.5%) and echinocandins (47.5%) were the most frequently administered monotherapies. Among the 15 reported species, 90-day survival was highest for patients infected with either C. parapsilosis (70.7%) or C. lusitaniae (74.5%) and lowest for patients infected with an unknown species (46.7%) or two or more species (53.2%). In conclusion, this study expands the current knowledge of the epidemiology and outcomes of invasive candidiasis caused by non-albicans species of Candida in North America. The variability in species distribution in these centers underscores the importance of local epidemiology in guiding the selection of antifungal therapy. Citation: Pfaller MA, Andes DR, Diekema DJ, Horn DL, Reboli AC, et al. (2014) Epidemiology and Outcomes of Invasive Candidiasis Due to Non-albicans Species of Candida in 2,496 Patients: Data from the Prospective Antifungal Therapy (PATH) Registry 2004–2008. PLoS ONE 9(7): e101510. doi:10.1371/journal.pone.0101510 Editor: Neeraj Chauhan, New Jersey Medical School, Rutgers University, United States of America Received February 5, 2014; Accepted June 6, 2014; Published July 3, 2014 Copyright: ß 2014 Pfaller et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This data collection and analysis was supported by Astellas Pharma, US. Billy Franks, an employee of Astellas Pharma., provided statistical analysis support as well as being involved in manuscript preparation and authorship. Statistical programming support was provided by Alan Fan from Astellas. Editorial support (including editing for journal style, collating comments, and routing reviews), funded by Astellas, was provided by Jonathon Gibbs BSc., a medical writer at Envision Scientific Solutions. Competing Interests: The authors have read the journal’s policy and declare the following conflicts: MAP has received grant support and sat on advisory boards for Astellas Pharma, Merck and Pfizer. He is a consultant for JMI laboratories. DRA has received grant support from Astellas Pharma and consultancy fees from Merck. He is also a member of the PLOS ONE editorial board. DJD has received grant support from Astellas. DLH is a principal of David Horn, LLC and CEO of a private company, Mid-Atlantic BioTherapeutics, Inc. He has received consultancy fees from Astellas Pharma. ACR has received grant support from Merck and T3 Biosystems. CR has received grant support and Honoraria from Astellas Pharma and Honoraria from Merck and Pfizer. BF and NEA are employees of Astellas Pharma. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials. * Email: michael-pfaller@uiowa.edu Introduction Candidemia and other forms of invasive candidiasis (IC; defined as candidemia or infection involving normally sterile sites) are unquestionably the most prevalent of the invasive mycoses worldwide [1,2]. More than 30 species of Candida have been reported to cause IC [3–6]. Candida albicans is the most common species encountered in most settings [7]. Other species include C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. lusitaniae, C. guilliermondii, and several other infrequently isolated species [4,8]. In addition, the use of molecular identification methods has resulted in the discovery of new species within the larger species complexes (e.g. C. dubliniensis within the C. albicans complex, C. fermentati within the C. guilliermondii complex, and C. nivariensis and C. bracarensis within the C. glabrata clade) [9–11]. Longitudinal surveillance studies from individual institutions, cities, countries, and broad geographic regions have documented the emergence of the various non-albicans Candida (N-CA) species as well as their potential to develop antifungal resistance [3,6,12– 21]. Resistance to fluconazole and echinocandins has been shown to be more common in N-CA species compared with C. albicans isolates in a population based laboratory study [13], and is in part due to N-CA species that are inherently resistant to antifungals, such as C. krusei to fluconazole [13] and the greater propensity of species such as C. glabrata to develop antifungal resistance [22]. Population-based surveillance of candidemia in the United States PLOS ONE | www.plosone.org 1 July 2014 | Volume 9 | Issue 7 | e101510