Yıl: 2023 Cilt: 49 Sayı: 1 Sayfa Aralığı: 1 - 8 Metin Dili: Türkçe DOI: 10.32708/uutfd.1191449 İndeks Tarihi: 23-06-2023

Akut Lösemili Kandidemi Olgularının Klinik Özelliklerinin Rektospektif Analizi: Tek Merkezli 8 Yıllık Deneyim

Öz:
Candida türleri hastanede yatan hastalarda özellikle hematolojik maligniteli hastalarda önde gelen invazif fungal enfeksiyon etkenidir. Bu çalışma, hematolojik maligniteli hastalarda kandidemi prevalansını, mortalite ile ilişkili kontrol edilebilir risk faktörlerini ve antifungal direnci belirlemeyi, ampirik antifungal tedaviye rehberlik edecek ve enfeksiyon kontrol stratejilerinin geliştirilmesine katkıda bulunacak bilgiler elde etmeyi amaçlamaktadır. Bursa Uludağ Üniversitesi Tıp Fakültesi Hastanesi Hematoloji Kliniğinde 2009-2016 yılları arasında Candida kan kültürü pozitif saptanan hematolojik maligniteli hastaların demografik verileri, laboratuvar sonuçları, antifungal duyarlılıkları ve tedavi sonuçları geriye dönük olarak incelendi. Hematolojik maligniteleri olan 2489 hastanın 45’inde 45 kandidemi atağı saptandı. Bu hastaların büyük çoğunluğu akut lösemi hastalarıydı (%75.5). Çalışmamızda hematolojik malignitesi olan hastalarda kandidemi insidansını %1.8 bulduk; akut lösemili hastalarda ise bu oran %2.3 idi. Hastaların tür dağılımında C. albicans dışı türler hakimdi (38/45, %84,4). Genel olarak yatan hastalara kıyasla hematolojik malignitesi olan hastalarda C. krusei ve C. tropicalis daha yaygındı. C. parapsilosis her iki grupta da kandidemi için yaygın bir etkendi. Antifungal direnç, flukonazole karşı sadece iki C. parapsilosis izolatında antifungal direnç gözlendi. Toplam 30 günlük ölüm oranı %55,5 idi. Mortalite ile ilişkili bağımsız risk faktörleri hipoalbuminemi, aktif hastalık, septik şok ve monoterapi almaktı. Sonuç olarak, tedavisindeki gelişmelere rağmen, kandida ilişkili mortalitede önemli bir azalma sağlanamamıştır. Kandidemi tedavisinde lokal epidemiyolojik çalışmalar hala önemini korumaktadır. C. parapsilosis, kötü kateter yönetiminin bir göstergesi olarak kabul edilir. Çalışmamızda C. parapsilosis yüksek oranda tespit edilmiş ve antifungale direnç gösteren tek tür olmuştur. Bu, kandidemi ile mücadelede iyi kateter yönetiminin öneminin yanı sıra ampirik antifungal tedavi stratejilerinde epidemiyolojik çalışmaların önemini vurgulamaktadır.
Anahtar Kelime: Kandidemi Hematolojik malignite Akut lösemi Mortalite Risk faktörleri Antifungal duyarlılık.

A Retrospective Analysis of the Clinical Features of Candidemia Cases with Acute Leukemia: Single-Center 8-Year Experience

Öz:
Candida species are the leading cause of invasive fungal infections in hospitalized patients, especially those with a hematological malignancy. The present study aims to determine the prevalence of candidemia, controllable risk factors associated with morta lity, and antifungal resistance in patients with hematological malignancy and in light of these information, to obtain information that would guide empirical antifungal treatment, and to contribute to development of infection control strategies as well. We retrospectively reviewed demographical data, laboratory results, antifungal susceptibility, and treatment outcomes of patients with hematological malignancy who were found to have positive blood culture results for Candida between 2009 and 2016 in Hematology Clinic of Uludağ University, Faculty of Medicine Hospital. 45 candidemia episodes were detected in 45 of 2489 patients with hematological malignancies. Majority of these patients had acute leukemia (%75.5). We found the incidence of candidemia in patients with hematological malignancy as %1.8; and this rate was %2.3 in patients with acute leukemia. Species other than C. albicans were dominant in the species distribution of the patients (38/45, 84.4%). C. krusei and C. tropicalis were more common among patients with a hematological malignancy in comparison to other inpatients in general. C. parapsilosis was a common agent for candidemia in both groups. Antifungal resistance was observed in only two C. parapsilosis isolates, against fluconazole. The overall 30-day mortality rate was %55.5. Independent risk factors associated with mortality were hypoalbuminemia, active disease, septic shock, and to receive monotherapy. In conclusion, despite improvements in its treatment, no significant reduction has been achieved in the associated mortality. Local epidemiological studies are still important in the treatment of candidemia. C. parapsilosis is considered to be an indicator of bad catheter management. In our study, C. parapsilosis was detected at a high rate, and it was the only species showing antifungal resistance. This underscores the significance of good catheter management in the fight against candidemia, as well as the importance of epidemiological studies in empirical antifungal treatment strategies.
Anahtar Kelime: Candidemia Hematological malignancy Acute leukemia Mortality Risk factors Antifungal susceptibility

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Baron EJ, Peterson LR, Finegold SM. Hospital Epidemiology. In: Bailey and Scott’s Diagnostic Microbiology. 9th ed. St Louis: Mosby-YEAR Book Inc, 1994; 41.
  • 2. Pappas PG, Kauffman CA, Andes DR, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis Off Publ Infect Dis Soc Am 2016;62(4):1-50.
  • 3. Edwards JE. Candida Species. In: Mandell, Douglas, and Bennett’s Principle and Practice of Infectious Diseases (Eds: Mandell GL, Bennett JE, Dolin R). Seventh Edition. Saunders Elsevier 2010, Philadelphia: 3225-3240.
  • 4. Luzzati R, Amalfitano G, Lazzarini L, et al. Nosocomial candidemia in non-neutropenic patients at an Italian tertiary care hospital. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol 2000;19(8):602–7.
  • 5. Harbarth S, Ruef C, Francioli P, Widmer A, Pittet D. Nosocomial infections in Swiss university hospitals: a multi-centre survey and review of the published experience. Swiss-Noso Network. Schweiz Med Wochenschr 1999;129(42):1521–8.
  • 6. Dixon DM, Rhodes JC, Fromtling RA. Taxonomy, classification, and morphology of the fungi. In: Murray PR, Baron EJ, Pfaller MA, Tenover FC, Yolken RH (eds), Manual of Clinical Microbiology. American Society for Microbiology, Washington DC 2003;1653-67.
  • 7. Mullen CA, Abd El-Baki H, Samir H, Tarrand JJ, Rolston KV. Non-albicans Candida is the most common cause of candidemia in pediatric cancer patients. Support Care Cancer Off J Multinatl Assoc Support Care Cancer 2003;11(5):321–5.
  • 8. Pappas PG. Invasive candidiasis. Infect Dis Clin North Am 2006;20(3):485–506.
  • 9. Zaoutis TE, Argon J, Chu J, Berlin JA, Walsh TJ, Feudtner C. The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin Infect Dis Off Publ Infect Dis Soc Am 2005;41(9):1232–9.
  • 10. Tissot F, Agrawal S, Pagano L, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica 2017;102(3):433–44.
  • 11. Ortega M, Marco F, Soriano A, et al. Candida species bloodstream infection: epidemiology and outcome in a single institution from 1991 to 2008. J Hosp Infect 2011;77(2):157–61.
  • 12. Cheng M-F, Yang Y-L, Yao T-J, et al. Risk factors for fatal candidemia caused by Candida albicans and non-albicans Candida species. BMC Infect Dis 2005; 5:22.
  • 13. CLSI. Reference method for broth dilution antifungal susceptibility testing of yeasts: approved standard-third edition. CLSI document M27-A3. Wayne, PA: Clinical and Laboratory Standards Institute, 2008.
  • 14. CLSI. Reference method for broth dilution antifungal susceptibility testing of yeasts: third informational supplement. CLSI document M27-S3. Clinical and Laboratory Standards Institute, Wayne, PA, 2008.
  • 15. Kazak E, Akın H, Ener B, et al. An investigation of Candida species isolated from blood cultures during 17 years in a university hospital. Mycoses 2014;57(10):623–9.
  • 16. Pfaller M, Neofytos D, Diekema D, et al. Epidemiology and outcomes of candidemia in 3648 patients: data from the Prospective Antifungal Therapy (PATH Alliance®) registry, 2004-2008. Diagn Microbiol Infect Dis 2012;74(4):323–31.
  • 17. Dewan E, Biswas D, Kakati B, Verma SK, Kotwal A, Oberoi A. Epidemiological and mycological characteristics of candidemia in patients with hematological malignancies attending a tertiary-care center in India. Hematol Oncol Stem Cell Ther 2015;8(3):99–105.
  • 18. Pagano L, Caira M, Candoni A, et al. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica 2006;91(8):1068–75.
  • 19. Wisplinghoff H, Seifert H, Wenzel RP, Edmond MB. Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States. Clin Infect Dis Off Publ Infect Dis Soc Am 2003;36(9):1103–10.
  • 20. Pasqualotto AC, Rosa DD, Medeiros LR, Severo LC. Candidaemia and cancer: patients are not all the same. BMC Infect Dis 2006; 6:50.
  • 21. Kontoyiannis DP, Vaziri I, Hanna HA, et al. Risk Factors for Candida tropicalis fungemia in patients with cancer. Clin Infect Dis Off Publ Infect Dis Soc Am 2001;33(10):1676–81.
  • 22. Ziglam HM, Gelly KJ, Olver WJ. A survey of the antibiotic treatment of febrile neutropenia in haematology units in the United Kingdom. Clin Lab Haematol 2005;27(6):374–8.
  • 23. Al-Anazi K, Al-Jasser A. Candidaemia in Patients with Haematological Disorders and Stem Cell Transplant. Libyan J Med 2006;140–55.
  • 24. Gamaletsou MN, Walsh TJ, Zaoutis T, et al. A prospective, cohort, multicentre study of candidaemia in hospitalized adult patients with haematological malignancies. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis 2014;20(1): O50-57.
  • 25. Pfaller MA, Pappas PG, Wingard JR. Invasive Fungal Pathogens: Current Epidemiological Trends. Clin Infect Dis 2006; 43:3-14.
  • 26. Maertens J. Evaluating prophylaxis of invasive fungal infections in patients with haematologic malignancies. Eur J Haematol 2007;78(4):275–82.
  • 27. Sipsas NV, Lewis RE, Tarrand J, et al. Candidemia in patients with hematologic malignancies in the era of new antifungalagents (2001-2007): stable incidence but changing epidemiology of a still frequently lethal infection. Cancer 2009;115(20):4745–52.
  • 28. Hajjeh RA, Sofair AN, Harrison LH, et al. Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program. J Clin Microbiol 2004;42(4):1519–27.
  • 29. Specchia G, Pastore D, Montagna MT, et al. Fungemia in acute leukemia patients: a single institution’s experience. New Microbiol 2004;27(4):407–10.
  • 30. Tortorano AM, Kibbler C, Peman J, Bernhardt H, Klingspor L, Grillot R. Candidaemia in Europe: epidemiology and resistance. Int J Antimicrob Agents 2006;27(5):359–66.
  • 31. Tortorano AM, Biraghi E, Astolfi A, et al. European Confederation of Medical Mycology (ECMM) prospective survey of candidaemia: report from one Italian region. J Hosp Infect 2002;51(4):297–304.
  • 32. Bouza E, Muñoz P. Epidemiology of candidemia in intensive care units. Int J Antimicrob Agents 2008;32 Suppl 2: S87-91.
  • 33. Maródi L, Johnston RB. Invasive Candida species disease in infants and children: occurrence, risk factors, management, and innate host defense mechanisms. Curr Opin Pediatr 2007;19(6):693–7.
  • 34. Puig-Asensio M, Ruiz-Camps I, Fernández-Ruiz M, et al. Epidemiology and outcome of candidaemia in patients with oncological and haematological malignancies: results from a population-based surveillance in Spain. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis 2015;21(5): 491.e1-10.
  • 35. DiNubile MJ, Hille D, Sable CA, Kartsonis NA. Invasive candidiasis in cancer patients: observations from a randomized clinical trial. J Infect 2005;50(5):443–9.
  • 36. Kaya D, Kaptanoğlu S, Üstüner Z, Ertör E. Nötropenik hasta örneklerinden izole edilen mayaların tiplendirilmesi ve flukonazole karşı direncin araştırılması. KLİMİK Derg 2001; 14: 14-6.).
  • 37. Slavin MA, Sorrell TC, Marriott D, et al. Candidaemia in adult cancer patients: risks for fluconazole-resistant isolates and death. J Antimicrob Chemother 2010;65(5):1042–51.
  • 38. Zhang XB, Yu SJ, Yu JX, Gong YL, Feng W, Sun FJ. Retrospective analysis of epidemiology and prognostic factors for candidemia at a hospital in China, 2000-2009. Jpn J Infect Dis. 2012; 65:510-5.
  • 39. Wang E, Farmakiotis D, Yang D, et al. The ever-evolving landscape of candidaemia in patients with acute leukaemia: non-susceptibility to caspofungin and multidrug resistance are associated with increased mortality. J Antimicrob Chemother 2015;70(8):2362–8.
  • 40. Cisterna R, Ezpeleta G, Telleria O, et al. Nationwide Sentinel Surveillance of Bloodstream Candida Infections in 40 Tertiary Care Hospitals in Spain. J Clin Microbiol 2010;48(11):4200–6.
  • 41. Dutta A, Palazzi DL. Candida non-albicans versus Candida albicans fungemia in the non-neonatal pediatric population. Pediatr Infect Dis J 2011;30(8):664–8.
  • 42. Nucci M, Anaissie E, Betts RF, et al. Early removal of central venous catheter in patients with candidemia does not improve outcome: analysis of 842 patients from 2 randomized clinical trials. Clin Infect Dis Off Publ Infect Dis Soc Am 2010;51(3):295–303.
  • 43. Girmenia C, Finolezzi E, Federico V. ınvasıve candıda ınfectıons ın patıents wıth haematologıcal malıgnancıes and hematopoıetıc stem cell transplant recıpıents: current epıdemıology and therapeutıc optıons. Mediterr j hematol ınfect dis 2011;3(1):e2011013.
APA demirayak d, Özkalemkaş F, Ener B, Ozkocaman V (2023). Akut Lösemili Kandidemi Olgularının Klinik Özelliklerinin Rektospektif Analizi: Tek Merkezli 8 Yıllık Deneyim. , 1 - 8. 10.32708/uutfd.1191449
Chicago demirayak dilay,Özkalemkaş Fahir,Ener Beyza,Ozkocaman Vildan Akut Lösemili Kandidemi Olgularının Klinik Özelliklerinin Rektospektif Analizi: Tek Merkezli 8 Yıllık Deneyim. (2023): 1 - 8. 10.32708/uutfd.1191449
MLA demirayak dilay,Özkalemkaş Fahir,Ener Beyza,Ozkocaman Vildan Akut Lösemili Kandidemi Olgularının Klinik Özelliklerinin Rektospektif Analizi: Tek Merkezli 8 Yıllık Deneyim. , 2023, ss.1 - 8. 10.32708/uutfd.1191449
AMA demirayak d,Özkalemkaş F,Ener B,Ozkocaman V Akut Lösemili Kandidemi Olgularının Klinik Özelliklerinin Rektospektif Analizi: Tek Merkezli 8 Yıllık Deneyim. . 2023; 1 - 8. 10.32708/uutfd.1191449
Vancouver demirayak d,Özkalemkaş F,Ener B,Ozkocaman V Akut Lösemili Kandidemi Olgularının Klinik Özelliklerinin Rektospektif Analizi: Tek Merkezli 8 Yıllık Deneyim. . 2023; 1 - 8. 10.32708/uutfd.1191449
IEEE demirayak d,Özkalemkaş F,Ener B,Ozkocaman V "Akut Lösemili Kandidemi Olgularının Klinik Özelliklerinin Rektospektif Analizi: Tek Merkezli 8 Yıllık Deneyim." , ss.1 - 8, 2023. 10.32708/uutfd.1191449
ISNAD demirayak, dilay vd. "Akut Lösemili Kandidemi Olgularının Klinik Özelliklerinin Rektospektif Analizi: Tek Merkezli 8 Yıllık Deneyim". (2023), 1-8. https://doi.org/10.32708/uutfd.1191449
APA demirayak d, Özkalemkaş F, Ener B, Ozkocaman V (2023). Akut Lösemili Kandidemi Olgularının Klinik Özelliklerinin Rektospektif Analizi: Tek Merkezli 8 Yıllık Deneyim. Uludağ Üniversitesi Tıp Fakültesi Dergisi, 49(1), 1 - 8. 10.32708/uutfd.1191449
Chicago demirayak dilay,Özkalemkaş Fahir,Ener Beyza,Ozkocaman Vildan Akut Lösemili Kandidemi Olgularının Klinik Özelliklerinin Rektospektif Analizi: Tek Merkezli 8 Yıllık Deneyim. Uludağ Üniversitesi Tıp Fakültesi Dergisi 49, no.1 (2023): 1 - 8. 10.32708/uutfd.1191449
MLA demirayak dilay,Özkalemkaş Fahir,Ener Beyza,Ozkocaman Vildan Akut Lösemili Kandidemi Olgularının Klinik Özelliklerinin Rektospektif Analizi: Tek Merkezli 8 Yıllık Deneyim. Uludağ Üniversitesi Tıp Fakültesi Dergisi, vol.49, no.1, 2023, ss.1 - 8. 10.32708/uutfd.1191449
AMA demirayak d,Özkalemkaş F,Ener B,Ozkocaman V Akut Lösemili Kandidemi Olgularının Klinik Özelliklerinin Rektospektif Analizi: Tek Merkezli 8 Yıllık Deneyim. Uludağ Üniversitesi Tıp Fakültesi Dergisi. 2023; 49(1): 1 - 8. 10.32708/uutfd.1191449
Vancouver demirayak d,Özkalemkaş F,Ener B,Ozkocaman V Akut Lösemili Kandidemi Olgularının Klinik Özelliklerinin Rektospektif Analizi: Tek Merkezli 8 Yıllık Deneyim. Uludağ Üniversitesi Tıp Fakültesi Dergisi. 2023; 49(1): 1 - 8. 10.32708/uutfd.1191449
IEEE demirayak d,Özkalemkaş F,Ener B,Ozkocaman V "Akut Lösemili Kandidemi Olgularının Klinik Özelliklerinin Rektospektif Analizi: Tek Merkezli 8 Yıllık Deneyim." Uludağ Üniversitesi Tıp Fakültesi Dergisi, 49, ss.1 - 8, 2023. 10.32708/uutfd.1191449
ISNAD demirayak, dilay vd. "Akut Lösemili Kandidemi Olgularının Klinik Özelliklerinin Rektospektif Analizi: Tek Merkezli 8 Yıllık Deneyim". Uludağ Üniversitesi Tıp Fakültesi Dergisi 49/1 (2023), 1-8. https://doi.org/10.32708/uutfd.1191449