Farklı Klinik Örneklerden İzole Edilen Candida Türlerinin Dağılımı ve Antifungal Duyarlılık Profilleri: 5 Yıllık Retrospoektif Analiz

Abstract

Amaç: Bu çalışmada Kocaeli Üniversite Hastanesinde Candida türlerinin dağılımının ve antifungal duyarlılık profillerinin değerlendirilmesi amaçlanmıştır. Yöntem: Kocaeli Üniversitesi Hastanesinde Ocak 2017-Aralık 2021 arası izole edilen Candida türlerinin dağılımı ve antifungal duyarlılık profili hakkında retrospektif bir çalışma yürütülmüştür. Toplanan klinik örnekler Sabouraud dekstroz agarda ekilmiş ve uygun sürede inkübe edilmiştir. Candida spp. MALDI-TOF MS yöntemi ile tanımlanmıştır. Antifungal duyarlılık profilleri ise VITEK 2 Compact sistemi (bioMérieux, Fransa) ile belirlenmiştir. Bulgular: Bu çalışmaya 1046 hastadan izole edilen toplam 1667 klinik örnek dahil edilmiştir. Klinik örneklerin %83,4'ü yetişkinlerden (≥18 yaş) ve %16,6'sı pediatrik gruptan (<18 yaş) alınmıştır. Tüm izolatların 1072'si (%64,3) C. albicans ve 596'sı (%35,7) non albicans-Candida (NAC) olarak tanımlanmıştır. Erişkinlerde en çok C. albicans izole edilirken, pediatrik gruptan en çok C. parapsilosis izole edilmiştir. Tanımlanan Candida spp.’lerin %88,7'si flukonazole duyarlı ve %9,3'ü dirençli idi. En yüksek flukonazol direnç oranı (%25,4) tüm bölümlerden izole edilen C. parapsilosis'te gözlendi. Vorikonazol direnç oranı %4,9 idi. Kaspofungin ve mikafungin duyarlılık oranları sırasıyla %94,7 ve %96 idi. Flusitozin ve amfoterisin B'nin direnç oranları sırasıyla %1,4 ve %4,5 idi. Sonuç: Bu çalışmada en sık görülen NAC türü C. parapsilosis olarak belirlenmiştir. Hastanemizde C. parapsilosis'in yüksek prevalansı ve yüksek flukonazol direnci, ampirik flukanozol tedavisinin tartışmalı olduğunu gösterebilir.

Keywords

• Candida türleri
• antifungal duyarlılık
• epidemiyoloji
• retrospektif

Distribution of Candida Species Isolated from Different Clincal Specimens and Their Antifungal Susceptibility Profile: A 5 Year Retrospective Analysis

Abstract

Objective: In this study it was aimed to evaluate the distribution of Candida species and their antifungal susceptibility profiles in Kocaeli University Hospital, Kocaeli, Turkey. Methods: A retrospective study on the distribution of Candida species and antifungal susceptibility profile were conducted from January 2017 to December 2021 in our laboratory. Different clinical samples collected were cultured on Sabouraud dextrose agar and incubated for an appropriate time. Candida spp. were identification by MALDI-TOF MS. And their antifungal susceptibility profile were determined by the VITEK 2 Compact system (BioMérieux, France). Results: Totally 1667 clinical samples isolated from 1046 patients were included in this study. Of Clinical samples, 83.4% were from adults (≥ 18years) and 16.6% from pediatric group (< 18 years). Among all isolates, 1072 (64.3%) were C. albicans and 596 (35.7%) were non albicans Candida (NAC) species. C. albicans was mostly isolated from adults, whereas C. parapsilosis was mostly isolated from pediatric group. Regardless of Candida species identified, 88.7% were susceptible and 9.3% were resistant to fluconazole. The highest fluconazole resistance rate (25.4%) was observed in C. parapsilosis isolated from all departments. Voriconazole resistance ratio was 4.9%. The susceptibility rate of caspofungin and micafungin were 94.7% and 96%, respectively. The resistance rates of flucytosine and amphotericin B were 1.4% and 4.5%, respectively. Conclusion: In present study, the most common NAC species was determined as C. parapsilosis. The high prevalence and high fluconazole resistance of C. parapsilosis in our hospital may demonstrate that empirical fluconazole treatment is debatable.

Keywords

• Candida species
• antifungal susceptibility
• epidemiology
• retrospective

References

1. Pfaller MA. Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. 2007;20(1):133-163.https://doi.org/10.1128
2. Rabih O. Darouiche. Candida in ICU. Clin Chest Med 2009 (30): 287–293 doi:10.1016/j.ccm.2009.02.013
3. Yeşilkaya A., Azap Ö., Aydın M., Akçil Ok. M. Epidemiology. species distribution. clinical characteristics and mortality of candidaemia in a tertiary care university hospital in Turkey. 2007-2014. Mycoses 2017; 60. 433–439. doi:10.1111/myc.12618
4. Vazquez J.A., Sobel J.D. 2011. Candidiasis. in:. pp. 167–206. doi:10.1007/978-1-4419-6640-7_11
5. Snydman DR. Shifting patterns in the epidemiology of nosocomial Candida infections. Chest. 2003;123: 500-503.https://doi.org/10.1378/chest.123.5_suppl.500S
6. Siddiqui A.H., Dabadghao S., Tewari A., Srivastava. V.K. Increasing Non-Albicans Candida in Hematological Patients with Fluconazole Prophylaxis: A Case Series. Indian Journ of Hem. and Blood Trans. 2017; 33. 624–625. doi:10.1007/s12288-016-0768-6
7. Enfert C. Kaune AK. Alaban LR. Chakraborty S. et al. The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives. FEMS Microbiol Rev. 2021;45(3):fuaa060. doi: 10.1093/femsre/fuaa060.
8. Seyoum E. Bitew A. Mihret A. Distribution of Candida albicans and non-albicans Candida species isolated in different clinical samples and their in vitro antifungal susceptibiliy profile in Ethiopia. BMC Infect Dis. 2020;20(1):231. doi: 10.1186/s12879-020-4883-5.

9. Moosa MY. Sobel JD. Non-albicans Candida infections in patients with hematologic malignancies. Semin Respir Infect. 2002;91-98. doi: 10.1053/srin.2002.33444.
10. Miceli MH. Díaz JA. Lee SA. Emerging opportunistic yeast infections. Lancet Infect Dis. 2011 Feb;11(2):142-151. doi: 10.1016/S1473-3099(10)70218-8.
11. Segrelles-Calvo G, Araújo GRS, Llopis-Pastor E, et al. Prevalence of opportunistic invasive aspergillosis in COVID-19 patients with severe pneumonia. Mycoses. 2021 Feb;64(2):144-151. doi: 10.1111/myc.13219.
12. DeorukhkarS.C. Saini S. Candidiasis: Past. present and future. Int J Infect Trop Dis 2015;2(1):12-24. doi: 10.14194/ijitd.2.1.2
13. Overview of antifungal ECOFFs and clinical breakpoints for yeasts, moulds and dermatophytes using the EUCAST E.Def 7.3. E.Def 9.3 and E.Def 11.0 procedures. European Committee on Antimicrobial Susceptibility Testing (EUCAST).
14. 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.
15. Öztürk T, Özseven AG, Sesli Çetin E, Kaya S. Kan kültürlerinden izole edilen Candida suşlarının tiplendirilmesi ve antifungal duyarlılıklarının araştırılması. Kocatepe Tıp Derg. 2013;14:17–22.
16. Keçeli, S.A., Dündar, D., Tamer, G.S. Comparison of Vitek Matrix-assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry Versus Conventional Methods in Candida Identification. Mycopathologia 2016: 181, 67–73.doi:10.1007/s11046-015-9944-8
17. De Francesco MA, Piccinelli G, Gelmi M, et al. Invasive Candidiasis in Brescia, Italy: Analysis of Species Distribution and Antifungal Susceptibilities During Seven Years. Mycopathologia. 2017;182(9-10):897-905. doi:10.1007/s11046-017-0155-3
18. Xiao M, Chen SC, Kong F, et al. Distribution and Antifungal Susceptibility of Candida Species Causing Candidemia in China: An Update From the CHIF-NET Study. J Infect Dis. 2020;221(Suppl 2):S139-S147. doi:10.1093/infdis/jiz573
19. Hazırolan G, Yıldıran D, Baran I, Mumcuoğlu I, Aksu N. Yatan hasta örneklerinden izole edilen Candida izolatlarının tür dağılımlarının ve antifungal duyarlılık profillerinin değerlendirilmesi. Turk Hij Den Biyol Derg. 2015;72(1):17-26
20. Çekin Y, Pekintürk N, Cekin AH. Evaluation of species distribution and antifungal resistance of Candida isolates from hospitalized patients. J Clin Anal Med. 2015; 6(1): 8-11.
21. d'Enfert C, Kaune AK, Alaban LR, et al. The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives. FEMS Microbiol Rev. 2021;45(3):fuaa060. doi:10.1093/femsre/fuaa060
22. Pammi, M., Holland, L., Butler, G., Gacser, A., Bliss, J.M.,. Candida parapsilosis Is a Significant Neonatal Pathogen. Ped. Infect. Dis. Journ. 2013; 32: 206–216. doi:10.1097/inf.0b013e3182863a1c.
23. Sarvikivi E, Lyytikainen O, Soll DR, et al. Emergence of fluconazole resistance in a Candida parapsilosis strain that caused infections in a neonatal intensive care unit. J Clin Microbiol. 2005;43:2729–2735.
24. Calgin MK, Cetinkol Y. Distribution and antifungal susceptibility patterns of Candida species at a university hospital in Northern Turkey. J Infect Dev Ctries. 2018;12(2):97-101. doi:10.3855/jidc.9698
25. Etiz P, Kibar F, Ekenoğlu Y, Yaman A. Kan kültürlerinden izole edilen Candida türlerinin dağılımının ve antifungal duyarlılıklarının retrospektif olarak değerlendirilmesi. ANKEM Derg. 2015;29(3):105-113
26. Fuller J, Dingle TC, Bull A, et al. Species distribution and antifungal susceptibility of invasive Candida isolates from Canadian hospitals: results of the CANWARD 2011-16 study. J Antimicrob Chemother. 2019;74(Suppl 4):iv48-iv54. doi:10.1093/jac/dkz287
27. Perlin DS, Rautemaa-Richardson R, Alastruey-Izquierdo A. The global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect Dis. 2017 17(12):e383-e392. doi: 10.1016/S1473-3099(17)30316-X.
28. Bayram Y, Gültepe B, Özlük S, Güdücüoğlu H. Çeşitli klinik örneklerden izole edilen Candida kökenlerinin identifikasyonu ve antifungal duyar¬lılıklarının araştırılması, Van Tıp Derg 2012;19(4): 177-181.
29. Kalantar E, Assadi M, Pormazaheri H, et al. Candida non albicans with a High amphotericin B resistance pattern causing candidemia among cancer patients. Asian Pac J Cancer Prev. 2014;15(24):10933-10935. doi: 10.7314/apjcp.2014.15.24.10933.
30. Colombo AL, Júnior JNA, Guinea J. Emerging multidrug-resistant Candida species. Curr Opin Infect Dis. 2017;30(6):528-538. doi: 10.1097/QCO.0000000000000411