Onaltı yıl boyunca hastanemizde rutin olarak test edilmiş olan invaziv Candida spp

DOI: 10.26650/cjm.2019.43.37Amaç: İnvaziv Candida infeksiyonları kritik veya bağışıklığı baskılanmış hastalarda sıklıkla yüksek morbidite ve mortaliteye sebep olurlar. Biz Cerrahpaşa Tıp Fakültesi mikoloji laboratuvarında 16 yıl boyunca hasta materyallerinden ayrılan 1371 invaziv Candida kökeninin tür dağılımı ve antifungal duyarlılık verilerini analiz ettik. Yöntemler: Duyarlılık testleri kandan veya derin vücut bölgelerinden ve/veya başlangıç antifungal tedaviye yanıtsız hastalardan ayrılan kökenlere yapıldı ve tüm sonuçlar rutin olarak klinisyenlere bildirildi. Amfoterisin B (AMB) ve azollere karşı testler 1998’den 2012’ye kadar Clinical and Laboratory Standards Institute (CLSI) rehberlerine göre ve 2012’den 2014’e kadar Etest kullanılarak yapıldı. Candida’ların ekinokandinlere duyarlılık testleri için 2012’den 2014’e kadar Sensititre YeastOne (SYO) yöntemi kullanıldı. Bu retrospektif analizde, sistemik antifungallere direnç önceki ve yeni gözden geçirilmiş CLSI direnç sınırları ile ve doğal olmayan fenotipler yönteme bağlı türe özgül epidemiyolojik eşik değerleri kullanılarak belirlendi. Bulgular: En sıklıkla ayrılan tür Candida albicans (%48)’ı C. parapislosis (20%), C. glabrata ve C. tropicalis (ikisi de 12%) izledi. CLSI’ın yeni önerdiği sınır değerleri kullanıldığında C. albicans, C. parapsilosis ve özellikle C. tropicalis’in (FLZ)’e direnç yüzdeleri değişti. Epidemiyolojik eşik değerleri kullanıldığında bütün türler içerisinde FLZ’e azalmış duyarlılık C. albicans kökenlerinde daha yüksek (%33.4) bulunurken C. glabrata için itrakonazol (ITZ)’e azalmış duyarlılık daha yüksek (%58.1) olarak belirlendi. Sonuç: Yerel antifungal direnç ve duyarlılık paternlerinin bilinmesi klinik karar vermeyi etkileyebilir.Cite this article as: Kantarcıoğlu AS, Aygün G. A 16-year analysis of antifungal susceptibilities of invasive Candida spp tested in our daily hospital routine. Cerrahpasa Med J 2019; 43(1): 13-22.

A 16-Year Analysis of Antifungal Susceptibilities of Invasive Candida spp Tested in Our Daily Hospital Routine

DOI: 10.26650/cjm.2019.43.37Objective: Invasive Candida infections often cause high morbidity and mortality especially in the critically ill or immunosuppressive patients. We analyzed the species distribution and antifungal susceptibility data of 1371 invasive Candida strains isolated in Cerrahpasa Medical Faculty mycology laboratory over 16 years. Methods: We performed susceptibility tests for the strains isolated from blood or deep sites and/or from patients unresponsive to the initial antifungal treatment, and all results were routinely reported to clinicians. The tests against amphotericin B (AMB) and azoles were performed using Clinical and Laboratory Standards Institute (CLSI) guidelines from 1998 to 2012 and using Etest from 2012 to 2014. The Sensititre YeastOne (SYO) colorimetric method was used to test Candida echinocandin susceptibility between 2012 and 2014. In this retrospective analysis, resistance or non-wild type (non-WT) phenotypes to systemic antifungals were determined by the previous and recently revised CLSI breakpoints (BPs) and by method-dependent species-specific epidemiological cutoff values (ECVs), respectively. Results: Overall, Candida albicans was the most commonly isolated species (48%) followed by C. parapsilosis (20%), C. glabrata (12%), and C. tropicalis (12%). The new epidemiological BPs provided by CLSI changed the percentage of resistant C. albicans, C. parapsilosis, and particularly C. tropicalis isolates to fluconazole (FLZ). Using the ECVs, reduced susceptibility to FLZ was higher among C. albicans isolates (33.4%), whereas itraconazole (ITZ) was higher in C. glabrata (58.1%) than in all other species.  Conclusion: Antifungal susceptibility tests are a key component of the care of patients with invasive candidiasis. Knowledge of local prevalence of antifungal resistance and susceptibility patterns might affect clinical decision-making. Cite this article as: Kantarcıoğlu AS, Aygün G. A 16-year analysis of antifungal susceptibilities of invasive Candida spp tested in our daily hospital routine. Cerrahpasa Med J 2019; 43(1): 13-22.

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  • 1. Beardsley J, Halliday CL, Chen S C-A, Sorrel TC. Responding to the emergence of antifungal drug resistance: perspectives from the bench and the bedside. Future Microbiol 2018; 13: 1175-91. 2. National Committee for Clinical Laboratory Standards. 1997. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard, 2nd ed. M27-A. National Committee for Clinical Laboratory Standards, Wayne, Pa. 3. National Committee for Clinical Laboratory Standards. 2002. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard, 2nd ed. M27-A2. National Committee for Clinical Laboratory Standards, Wayne, Pa. 4. Clinical Laboratory Standards Institute. 2008. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard, 3rd ed. CLSI document M27-A3. Clinical Laboratory Standards Institute, Wayne, PA. 5. Clinical Laboratory Standards Institute. 2008. Reference method for broth dilution antifungal susceptibility testing of yeasts; third informational supplement. CLSI M27-S3. Clinical Laboratory Standards Institute, Wayne, PA. 6. Clinical Laboratory Standards Institute. 2012. Reference method for broth dilution antifungal susceptibility testing of yeasts; fourth informational supplement. CLSI M27-S4. Clinical Laboratory Standards Institute, Wayne, PA. 7. Clinical Laboratory Standards Institute. 2016. Epidemiological cutoff values for antifungal susceptibility testing. CLSI M59. 1st ed. Clinical Laboratory Standards Institute, Wayne, PA. 8. Espinel-Ingroff A, Alvarez-Fernandez M, Cantón E, Carver PL, Chen SC, Eschenauer G, et al. A multicenter study of epidemiological cutoff values and detection of resistance in Candida spp. to anidulafungin, caspofungin, and micafungin using the Sensitire YeastOne Colorimetric method. Antimicrob Agents Chemother 2015; 59: 6725-32. 9. Espinel-Ingroff A, Turnidge J. The role of epidemiological cutoff values (ECVs/ECOFFs) in antifungal susceptibility testing and interpretation for uncommon yeasts and molds. Rev Iberoam Micol 2016; 33: 63-75. 10. Espinel-Ingroff A, Arendrup M, Cantón E, Cordoba S, Dannaoui E, García-Rodríguez J, et al. Multicenter study of method-dependent epidemiological cutoff values for detection of resistance in Candida spp. and Aspergillus spp. to amphotericin B and echinocandins for the Etest agar diffusion method. Antimicrob Agents Chemother 2017; 61: 1-10. 11. Lodder J. The Yeasts. A Txonomic Study. 1st ed. American Elsevier Publishing Company, New York, 1970. 12. Hazen KC. New and emerging yeast pathogens. Clin Microbiol Rev 1995; 8: 462-78. 13. Yarrow D. Methods for the isolation, maintenance and identification of yeasts. In The Yeasts. A Taxonomic study, 4th edn (Kutzman CP & Fell JW Eds). Amsterdam, The Netherlands. Elsevier Science 1998: 77-100. 14. Kutzman CP, Fell JW. The Yeasts. A Taxonomic Study. Amsterdam, The Netherlands. Elsevier, 1998. 15. Warren NG, Hazen KC. Candida, Cryptococcus, and other yeasts of medical importance. In Murray PR, Baron EJ, Pfaller MA, Tenover FC, Yolken RH (Eds.). Manual of Clinical Microbiology 7th edn (ASM Press, Washington, DC, USA) 2012: 1184-99. 16. Pfaller MA, Espinel-Ingroff A, Canton E, Castanheira M, Cuenca-Estrella M, Diekema DJ, et al. Wild-type MIC distributions and epidemiological cutoff values for amphotericin B, flucytosine, and itraconazole and Candida spp. as determined by CLSI broth microdilution. J Clin Microbiol 2012; 50: 2040-45. 17. Eschenauer GA, Nguyen MH, Shoham S, Vazquez JA, Morris AJ, Pasculle WA, et al. Real-world experience with echinocandin MICs against Candida species in a multicenter study of hospitals that routinely perform susceptibility testing of bloodstream isolates. Antimicrob Agents Chemother 2014; 58: 1897-1906. 18. De Francesco MA, Piccinelli G, Gelmi M, Gargiulo F, Ravizzola G, Pinsi G, et al. Invasive candidiasis in Brescia Italy: Analysis of species distribution and antifungal susceptibilities over seven years. Mycopathologia 2017; 182; 897-905. 19. Li W, Hu YA, Li FQ, Shi LN, Shao HF, Huang M, et al. Distribution of yeast isolates from invasive infections and their in vitro susceptibility to antifungal agents: evidence from 299 cases in a 3-year (2010 to 2012) surveillance study. Mycopathologia 2015; 179: 397-405. 20. Sanguinetti M, Posteraro B, Fiori B, Ranno S, Torelli R, Fadda G. Mechanisms of azole resistance in clinical isolates of Candida glabrata collected during a hospital survey of antifungal resistance. Antimicrom Agents Chemother 2005; 49: 668-79. 21. Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ, Lortholary O, et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 2012; 18: 19-37. 22. Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, et al. Clinical practice guidelines for the diagnosis and management of candidiasis: 2009 update by the Infectious Disease Society of America. Clin Infect Dis 2009; 48: 503-35. 23. Ullmann AJ, Akova M, Herbrecht R, Viscoli C, Arendrup MC, Arikan-Akdagli S, et al. ESCMID guideline for the diagnosis and management of candidiasis: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT). Clin Microbiol Infect 2012; 18: 53-67. 24. Pfaller MA, Diekema DJ, Andes D, Arendrup MC, Brown SD, Lockhart SR, et al. Clinical breakpoints for the echinocandins and Candida revisited: integration of molecular, clinical and microbiological data to arrive at species specific interpretive criteria. Drug Resist Updat 2011; 164-76. 25. Espinel-Ingroff A, Arendrup MC, Pfaller MA, Bonfietti LX, Bustamante B, Canton E, et al. Interlaboratory variability of caspofungin MICs for Candida spp. using CLSI and EUCAST methods: should the clinical laboratory be testing this agent? Antimicrob Agents Chemother 2013; 57: 5836-42. 26. Pfaller MA, Messer SA, Diekema DJ, Jones RN, Castanheira M. Use of micafungin as a surrogate marker to predict susceptibility and resistance to caspofungin among 3764 clinical isolates of Candida by use of CLSI methods and interpretive criteria. J Clin Microbiol 2014; 52: 108-14. 27. Pfaller MA, Diekema DJ, Jones RN, Castanheira M. Use of anidulafungin as a surrogate marker to predict susceptibility and resistance to caspofungin among 4290 clinical isolates of Candida by use of CLSI methods and interpretive criteria. J Clin Microbiol 2014; 52: 3223-9. 28. Pfaller MA, Castanheira M, Diekema DJ, Messer SA, Moet GJ, Jones RN. Comparison of European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Etest methods with the CLSI broth microdilution method for echinocandin susceptibility testing of Candida species. J Clin Microbiol 2010; 48: 1592-9.