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

Year 2019, Volume: 43 Issue: 1, 13 - 22, 01.07.2019

Abstract

DOI: 10.26650/cjm.2019.43.37


Objective: 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.

References

  • 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.

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

Year 2019, Volume: 43 Issue: 1, 13 - 22, 01.07.2019

Abstract

DOI: 10.26650/cjm.2019.43.37


Amaç: 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.

References

  • 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.
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Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Araştırmalar
Authors

A Serda Kantarcıoğlu This is me

Gökhan Aygün This is me

Publication Date July 1, 2019
Published in Issue Year 2019 Volume: 43 Issue: 1

Cite

APA Kantarcıoğlu, A. S., & Aygün, G. (2019). Onaltı yıl boyunca hastanemizde rutin olarak test edilmiş olan invaziv Candida spp. Cerrahpaşa Tıp Dergisi, 43(1), 13-22.
AMA Kantarcıoğlu AS, Aygün G. Onaltı yıl boyunca hastanemizde rutin olarak test edilmiş olan invaziv Candida spp. Cerrahpaşa Tıp Dergisi. July 2019;43(1):13-22.
Chicago Kantarcıoğlu, A Serda, and Gökhan Aygün. “Onaltı yıl Boyunca Hastanemizde Rutin Olarak Test Edilmiş Olan Invaziv Candida Spp”. Cerrahpaşa Tıp Dergisi 43, no. 1 (July 2019): 13-22.
EndNote Kantarcıoğlu AS, Aygün G (July 1, 2019) Onaltı yıl boyunca hastanemizde rutin olarak test edilmiş olan invaziv Candida spp. Cerrahpaşa Tıp Dergisi 43 1 13–22.
IEEE A. S. Kantarcıoğlu and G. Aygün, “Onaltı yıl boyunca hastanemizde rutin olarak test edilmiş olan invaziv Candida spp”, Cerrahpaşa Tıp Dergisi, vol. 43, no. 1, pp. 13–22, 2019.
ISNAD Kantarcıoğlu, A Serda - Aygün, Gökhan. “Onaltı yıl Boyunca Hastanemizde Rutin Olarak Test Edilmiş Olan Invaziv Candida Spp”. Cerrahpaşa Tıp Dergisi 43/1 (July 2019), 13-22.
JAMA Kantarcıoğlu AS, Aygün G. Onaltı yıl boyunca hastanemizde rutin olarak test edilmiş olan invaziv Candida spp. Cerrahpaşa Tıp Dergisi. 2019;43:13–22.
MLA Kantarcıoğlu, A Serda and Gökhan Aygün. “Onaltı yıl Boyunca Hastanemizde Rutin Olarak Test Edilmiş Olan Invaziv Candida Spp”. Cerrahpaşa Tıp Dergisi, vol. 43, no. 1, 2019, pp. 13-22.
Vancouver Kantarcıoğlu AS, Aygün G. Onaltı yıl boyunca hastanemizde rutin olarak test edilmiş olan invaziv Candida spp. Cerrahpaşa Tıp Dergisi. 2019;43(1):13-22.