Epidemiology of Candida bloodstream infections and antifungal susceptibility proiles: 10-year experience with 381 candidemia episodes in a tertiary care university centre Sehnaz ALP, Sevtap ARIKAN-AKDAGLI, Dolunay GULMEZ, Sibel ASCIOGLU, Omrum UZUN, Murat AKOVA Hacettepe University Faculty of Medicine, Ankara, Turkey Candida spp. are the most common fungal pathogens responsible for invasive diseases in humans. Among them, Candida albicans is in general responsible for more than half of all Candida infections. However, recent studies showed a remarkable shift from C.albicans to non-albicans Candida species (NAC) at least in a number of centres. Candida krusei is known to be intrinsically resistant to luconazole. Moreover, a decreased susceptibility to luconazole among other NAC, especially for Candida glabrata has been reported. The changing epidemiology of candidemia and antifungal susceptibility data have an impact on the preferred empirical antifungal regimen. This study was undertaken to (i) state the ranking of Candida isolates among all positive blood cultures in our centre; ii) deine the species distribution of Candida strains responsible for bloodstream infections and explore whether there is any potential increase in non-albicans Candida as compared to C. albicans; and to (iii) determine the inluence of currently approved CLSI breakpoints on interpretation of antifungal susceptibility test (AST) results. We retrospectively evaluated our database and records of Mycology Laboratory from January 2001 to December 2010. Patients who were reported to have at least one positive blood culture yielding Candida species were included in the study. In case of multiple candidemia episodes during the same course, only the irst episode was included. AST results obtained from the archive of Mycology Laboratory were interpreted according to currently approved CLSI breakpoints. During the study period, there were 18.426 positive blood cultures of which 858 grew Candida spp. For the current analysis 381 candidemia episodes were included. Candida ranked the ifth (ranged 4-7 during individual years) frequent cause of bloodstream infection. The distribution of species in 381 candidemia episodes and ranking of Candida isolates among all positive blood cultures are shown in Table-1. (1) Candida spp. play a prominent role among the common bloodstream isolates in our centre. (2) Among all Candida species, C. albicans has been the most common cause of candidemia and this trend has not changed during the study period. (3) Resistance to tested antifungal drugs is not common among our candidemia isolates except for itraconazole. (4) We observed decreased susceptibility to luconazole for our C.glabrata strains. This is possibly due to the intrinsic feature of this species for susceptibility to luconazole and the conclusive nonexistence of the category of “susceptible” in the currently revised breakpoint scale. References 1. Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard, 3rd ed., CLSI document M27-A3. Clinical and Laboratory Standards Institute 2008, Wayne, PA. 2. Cuenca-Estrella M, Bernal-Martinez L, Buitrago MJ, et al. Update on the epidemiology and diagnosis of invasive fungal infection. Int J Antimicrob Agents 2008;32 Suppl 2:S143-7. 3. Nguyen MH, Peacock JE, Morris AJ, et al. The changing face of candidemia: emergence of non-Candida albicans species and antifungal resistance. Am J Med 1996;100:617-23. 4. Pfaller MA, Andes D, Diekema DJ, Espinel-Ingroff A, Sheehan D; CLSI Subcommittee for Antifungal Susceptibility Testing. -Wild-type MIC distributions, epidemiological cutoff values and species-speciic clinical breakpoints for luconazole and Candida: time for harmonization of CLSI and EUCAST broth microdilution methods. Drug Resist Updat 2010;13:180-95. 5. Pfaller MA, Castanheira M, Messer SA, Moet GJ, Jones RN. Echinocandin and triazole antifungal susceptibility proiles for Candida spp., Cryptococcus neoformans, and Aspergillus fumigatus: application of new CLSI clinical breakpoints and epidemiologic cutoff values to characterize resistance in the SENTRY Antimicrobial Surveillance Program (2009). Diagn Microbiol Infect Dis 2011;69:45-50. Methods Results Table-1. Distribution of candidemia episodes (n=381) according to isolated Candida species *Other non-albicans Candida species (NAC) included in this study were: 4 C.guilliermondii, 4 C.lusitaniae, 2 C.inconspicua/norvegensis, 2 C.rugosa, 1 C.dubliniensis, 1 C.colliculosa Table-2. The number of Candida isolates with available AST results interpreted according to currently approved CLSI breakpoints* Antifungal drug Candida species (n) Currently approved CLSI Antifungal drug Candida species (n) Currently approved CLSI S SDD I R S SDD I R Fluconazole C.albicans (122) 119 2 - 1 Voriconazole C.albicans (92) 92 - - - C.glabrata (12) - 11 - 1 C.glabrata (10) IE IE IE IE C.krusei (5) PT PT PT PT C.krusei (4) 3 IE 1 - C.parapsilosis (22) 20 2 - - C.parapsilosis (17) 17 - - - C.tropicalis (18) 17 1 - - C.tropicalis (15) 15 - - - Itraconazole C.albicans (93) 88 4 - 1 Caspofungin C.albicans (45) 45 - - - C.glabrata (8) 1 6 - 1 C.glabrata (4) 2 - 2 - C.krusei (3) 1 1 - 1 C.krusei (3) 2 - 1 - C.parapsilosis (18) 16 2 - - C.parapsilosis (29) 28 - 1 - C.tropicalis (21) 11 6 - 4 C.tropicalis (13) 13 - - - *Per the absence of any speciic recommended breakpoints, species other than C.albicans, C.glabrata, C.krusei, C.parapsilosis and C.tropicalis were not included in the susceptibility proile analysis CLSI: Clinical and Laboratory Standards Institute S: Susceptible SDD: Susceptible dose dependent I: Intermediate R: Resistant PT: Poor target to be treated with the denoted drug IE: Insuficient evidence Species 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 Total n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) C.albicans 13 (50.0) 21 (61.8) 14 (66.7) 23 (65.7) 34 (58.6) 35 (62.5) 31 (65.9) 16 (42.1) 16 (51.6) 19 (54.3) 222 (58.3) C.parapsilosis 3 (11.5) 8 (23.5) 2 (9.5) 3 (8.6) 6 (10.3) 6 (10.7) 9 (19.1) 9 (23.7) 4 (12.9) 8 (22.9) 58 (15.2) C.tropicalis 3 (11.5) 2 (5.9) 5 (23.8) 4 (11.4) 11 (18.9) 11 (19.6) 4 (8.5) 6 (15.8) 4 (12.9) 1 (2.9) 51 (13.4) C.glabrata 3 (11.5) 1 (2.9) - 3 (8.6) 2 (3.4) 3 (5.4) 1 (2.1) 5 (13.2) 4 (12.9) 4 (11.4) 26 (6.8) C.krusei - - - - 1 (1.7) 1 (2.1) 2 (5.3) - 1 (2.9) 5 (1.3) C.kefyr 1 (3.8) - - - - - 1 (2.1) - 2 (6.5) 1 (2.9) 5 (1.3) Other NAC* 3 (11.5) 2 (5.9) - 2 (5.7) 4 (6.9) 1 (1.8) - - 1 (3.2) 1 (2.9) 14 (3.7) Total 26 34 21 35 58 56 47 38 31 35 381 Ranking among all positive blood cultures 6 4 7 7 4 4 6 6 4 6 5 C.albicans was always the dominant one [p-value for trend test between years 2001-2010 for C.albicans and non-albicans Candida species (NAC) was non-signiicant (p>0.05)]. There were 213 Candida strains with available AST results (123 C.albicans, 37 Candida parapsilosis, 27 Candida tropicalis, 12 C. glabrata, 5 C. krusei, 3 Candida kefyr, 3 Candida guilliermondii and one of each Candida dubliniensis, Candida lusitaniae, Candida rugosa). Among them, there were 188 isolates tested against luconazole, 145 isolates tested against voriconazole, 151 isolates tested against itraconazole and 99 isolates tested against caspofungin. Available AST results interpreted according to the currently approved species-speciic CLSI breakpoints are given in Table-2. Conclusions Introduction and Purpose