Yatan hasta örneklerinden izole edilen Candida izolatlarının tür dağılımlarının ve antifungal duyarlılık profillerinin değerlendirilmesi

Abstract

Amaç: Ciddi ya da invazif Candida enfeksiyonları, başta nötropenik hastalar olmak üzere genel olarak bağışıklık sisteminin baskılandığı, “özel konak” olarak tanımlanan hasta gruplarında sıklıkla gelişmekte ve yüksek mortalite oranı ile seyretmektedir. Ancak son iki dekattır ciddi Candida enfeksiyonlarının yalnızca nötropenik hasta ve özel konakla ilişkili bir klinik tablo olmadığı, özellikle hastanede yatan tüm kritik hastalarda gelişebileceği bilinmektedir. Bu çalışmada, hastanemizde yatan hastaların çeşitli klinik örneklerinden izole edilen Candida türlerinin tiplendirilerek antifungal duyarlılıklarının araştırılması hedeflenmiştir. Yöntemler: Şubat 2013 - Şubat 2014 tarihleri arasında, Ankara Numune Eğitim ve Araştırma Hastanesinde yatan hastaların çeşitli klinik örneklerinden üreyen 187 örnek çalışmaya dahil edilmiş ve retrospektif olarak incelenmiştir. Laboratuvara gönderilen klinik örnekler, Sabouraud dekstroz agar BD Diagnostic Systems ve koyun kanlı agar besiyerine BD Diagnostic Systems mantar aranması amacıyla ekilmiştir. İzole edilen maya mantarlarına Gram boyama ve germ tüp testi uygulanmıştır. Mayaların tanımlanması ve antifungal duyarlılık testleri için Vitek 2 Biomerieux otomatize sistemi kullanılmıştır.Bulgular: Toplam 187 izolatın 56’sı %29,9 C. albicans, 57’si %30,4 C. glabrata, 20’si %10,6 C. tropicalis, 12’si %6,4 C. parapsilosis 11’i %9,8 C. krusei, 11’i %5,8 C. kefyr, sekizi %4,2 C. famata, beşi %2,6 C. sphaerica, üçü %1,6 C. dubliniensis, biri %0,5 C. norvegensis, biri %0,5 C. lusitaniae, biri %0,5 C. guilliermondii, biri %0,5 C. haemulonii olarak tanımlanmıştır. Klinik örneklerin 107’si %57,3 yoğun bakım servislerinden izole edilmiştir. Tüm Candida türlerinde flukonazol, vorikonazol, amfoterisin B, flusitozin, ve kaspofungin için elde edilen duyarlılık oranları sırasıyla %92,52, %98,85, %95,97, %91,95 ve %100 olarak saptanmıştır. Sonuç: Candida türlerinin tiplendirilmesi ve antifungal duyarlılıklarının bildirilmesi, tedaviyi yönlendirmek için önem arz etmektedir. Etkin ve doğru enfeksiyon kontrol stratejileri geliştirebilmek adına, hastanelerin enfeksiyon etkenlerinin dağılımını ve bunların direnç paternlerini bilmesi gerekmektedir.

Keywords

• Candida, tür dağılımı, antifungal duyarlılık profili

Evaluation of species distribution and anti fungal susceptibility profiles of Candida isolates from hospitalized patients

Abstract

Objective: Serious or invasive Candida infections, often occur in immune suppressed patients like neutropenic patients and cause high mortality rates. However in the last two decades it is known that serious Candida infections are not a clinical condition associated with specific hosts like neutropenic patients, they can develop in any critically ill patients. In this study, we aimed to investigate types of Candida species isolated from clinical materials of hospitalized patients and determine their antifungal susceptibilities. Methods: 187 specimens isolated from various specimens of hospitalized patients in Ankara Numune Training and Research Hospital between February 2013 and February 2014 were included to this study and examined retrospectively. Clinical specimens sent to our laboratory were inoculated to Sabouraud dextrose agar BD Diagnostic Systems and %5 sheep blood agar BD Diagnostic Systems for inspection of yeast species. Gram staining and germ tube tests were applied to isolated yeasts. Vitek 2 Biomerieux automated system was used for identification and antifungal susceptibility test of yeasts. Results: A total of 187 isolates were distributed as follows: 56 29.9% C. albicans, 57 30.4% C. glabrata, 20 10.6% C. tropicalis, 12 6.4% C. parapsilosis, 11 5.8% C. krusei, 11 5.8% C. kefyr, 8 4.2% C. famata, 5 2.6% C. sphaerica, 3 1.6% C. dubliniensis, 1 0.5 % C. norvegensis, 1 0.5% C. lusitaniae, 1 0.5% C. guilliermondii and 1 0.5% C. haemulonii. 107 57,3% of species were isolated from ICUs. Antifungal susceptibility results for fluconazole, voriconazole, amphotericine B, flucytosine and caspofungine were 92.52%, 98.85%, 95.97%, 91.95% and %100 respectively. Conclusion: Identification and antifungal susceptibility testing are important for management of appropriate therapy. In order to develop effective and true infection control strategies, distribution of infective agents in hospitals and antimicrobial resistance patterns should be known.

Keywords

• Candida, species distribution, antifungal susceptibility profiles

References

1. 1. Cornely OA. Aspergillus to zygomycetes: causes, risk faktors, prevention, and treatment of invasive fungal infections. Infection, 2008; 36 (4): 296-313.
2. 2. Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent problem. Clin Microbiol Rev, 2007; 20 (1): 133–63.
3. 3. Pappas PG. Invasive candidiasis. Infect Dis Clin North Am, 2006; 20 (3): 485–506.
4. 4. Diekema D, Arbefeville S, Boyken L, Kroeger J, Pfaller M. The changing epidemiology of healthcare-associated candidemia over three decades. Diagn Microbiol Infect Dis, 2012; 73 (1): 45–8.
5. 5. Lewis RE. Overview of the changing epidemiology of candidemia. Curr Med Res Opin, 2009; 25 (7): 1732–40.
6. 6. Hazen KC, Howell SA. Candida, Cryptococcus ve Tıbbi Önemi Olan Diğer Mayalar, 9ncu baskı, Ankara: Atlas Kitapçılık, 2009.
7. 7. Dignani MC, Solomkin JS, Anaissie EJ. Clinical Mycology. 2nd, Churchill Livingstone: Elsevier Inc, 2009.
8. 8. Anonymous. Reference method for broth dilution antifungal susceptibility testing of yeasts, approved standard. CLSI Document M27-A3. Clinical and Laboratory Standards Institute, Wayne, PA, 2008.

9. 9. Rex JH, Pfaller MA, Walsh TJ, Chaturvedi V, Espinel-Ingroff A, Ghannoum MA, et al. Antifungal susceptibility testing: practical aspects and current challenges. Clin Microbiol Rev, 2001; 14 (4): 643-58.
10. 10. Anonymous. Method for antifungal disk diffusion susceptibility testing of yeasts; Approved Guideline 2nd, CLSI document M44-A2. Clinical and Laboratory Standards Institute, Wayne, Pa, 2009.
11. 11. Anonymous. Refererence method for broth dilution antifungal susceptibility testing of yeast; approved Standard, 3rd ed. CLSI document M27-S3. Clinical and Laboratory Standards Institute, Wayne, Pa. 2008.
12. 12. Cuenca-Estrella M, Gomez-Lopez A, AlastrueyIzquierdo A, Bernal-Martinez L, Cuesta I, Maria J, et al. Comparison of the Vitek 2 antifungal susceptibility system with the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution reference methods and with the sensititre yeast one and Etest techniques for in vitro detection of antifungal resistance in yeast isolates. Clin Microbiol, 2010; 48 (5): 1782–6.
13. 13. Pfaller MA, Moet GJ, Messer SA, Jones RN, Castanheira M. Geographic variations in species distribution and echinocandin and azole antifungal resistance rates among Candida bloodstream infection isolates: report from the SENTRY Antimicrobial Surveillance Program (2008 to 2009). J Clin Microbiol, 2011; 49 (1): 396-9.
14. 14. Yapar N, Pullukcu H, Avkan-Oguz V, Sayin-Kutlu S, Ertugrul B, Sacar S. Evaluation of species distribution and risk factors of candidemia: a multicenter case-control study. Med Mycol, 2011; 49 (1): 26–31.
15. 15. Çalışkan E, Dede A, Biten G. Kan Kültürlerinde saptanan Candida türlerinin dağılımı ve antifungal duyarlılıkları. ANKEM, 2013; 27 (1): 25-30.
16. 16. Rentz AM, Halpern MT, Bowden R. The impact of candidemia on length of hospital stay, outcome, and overall cost of illness. Clin Infect Dis, 1998; 27 (4): 781-8.
17. 17. Acar A, Öncül O, Küçükardalı Y, Özyurt M, Haznedaroğlu T, Çavuşlu Ş. Yoğun bakım ünitelerinde saptanan Candida enfeksiyonlarının epidemiyolojik özellikleri ve mortaliteye etki eden risk faktörleri. Mikrobiyol Bul, 2008; 42(3): 451-61.
18. 18. 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.
19. 19. Wang H, Xiao M, Chen SC, Kong F, Sun ZY, Liao K, et al. In vitro susceptibilities of yeast species to fluconazole and voriconazole as determined by the 2010 National China Hospital Invasive Fungal Surveillance Net (CHIF-NET) study. J Clin Microbiol, 2012; 50 (12): 3952-9.
20. 20. Azevedo AC, Bizerra FC, da Matta DA, de Almeida LP, Rosas R, Colombo AL. In vitro susceptibility of a large collection of Candida strains against fluconazole and voriconazole by using the CLSI disk diffusion assay. Mycopathologia, 2011; 171 (6): 411-6.
21. 21. Odds FC, Hanson MF, Davidson D, Jacobsen MD, Wright P, Whyte JA, et al. One year prospective survey of Candida bloodstream infections in Scotland. J Med Microbiol, 2007; 56 (8): 1066-75.
22. 22. Messer SA, Jones RN, Moet GJ, Kirby JT, Castanheira M. Potency of anidulafungin compared to nine other antifungal agents tested against Candida spp., Cryptococcus spp., and Aspergillus spp. results from the global SENTRY Antimicrobial Surveillance Program (2008) J Clin Microbiol, 2010; 48 (8): 2984–7.
23. 23. Sook-In J, Jong HS, Hyun-Jung C, Min-Young JMS, Soo-Hyun K, Wee Gyo L, et al. Korean Study Group for Candidemia. Antifungal susceptibility to amphotericin B, fluconazole, voriconazole, and flucytosine in Candida bloodstream isolates from 15 tertiary hospitals in Korea. Ann Lab Med, 2012; 32(6): 426–8.
24. 24. Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis, 2009; 48 (5): 503-35.
25. 25. Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev, 2007; 20 (1): 133-63.
26. 26. Doğruman AL, Aktaş AE, Tuncel E, Ayyıldız A, Yiğit N. Yenidoğan kan kültürlerinden izole edilen Candida kökenlerinin standart makrodilüsyon ve E test yöntemleriyle antifungal duyarlılıklarının saptanması. XXIX. Türk Mikrobiyoloji Kongresi. 8-13 Ekim, Antalya-Türkiye. 2000.
27. 27. Fındık D, Tuncer İ, Arslan U. Candida albicans türü maya mantarlarında antifungal ilaç direnci. XXIX. Türk Mikrobiyoloji Kongresi. Ekim 8-13, Antalya– Türkiye. 2000.
28. 28. Zer Y, Balcı İ. Yoğun Bakım ünitesindeki hastalardan izole edilen Candida suşlarının identifikasyonu ve antifungal duyarlılıkları. Türk Mikrobiyol Cem Derg, 2002; 32(3): 230-4.
29. 29. Cheng MF1, Yu KW, Tang RB, Fan YH, Yang YL, Hsieh KS. Distribution and antifungal susceptibility of Candida species causing candidemia from 1996 to 1999. Diagn Microbiol Infect Dis, 2004; 48 (1): 33-7.
30. 30. Sun HY, Singh N. Characterisation of breakthrough invasive mycoses in echinocandin recipients: an evidence-based review. Int J Antimicrob Agents, 2010; 35 (3): 211-8.
31. 31. Spiliopoulou A, Vamvakopoulou S, Bartzavali C, Dimitracopoulos G, Anastassiou ED, Christofidou M. Eleven- year retrospective survey of candidemia in a University Hospital in Southwestern Greece. Clin Microbiol Infect, 2010; 16 (9): 1378-81.
32. 32. Saracli MA, Gumral R, Gul HC, Gonlum A, Yildiran ST. Species distribution and in vitro susceptibility of Candida bloodstream isolates to six new and current antifungal agents in a Turkish tertiary care military hospital, recovered through 2001 and 2006. Mil Med, 2009; 174 (8): 860-5.