HASTANE KAYNAKLI KANDİDEMİ VE İNVAZİF ASPERGİLLOZİS TEDAVİSİ: GÜNCEL YAKLAŞIMLAR

İnvaziv fungal infeksiyonların (İFİ) immunsistemi baskılanmış hastalarda yönetimi çok önemli bir konudur. Candida spp. ve Aspergillus spp. hastane kaynaklı İFİ’in en sık görülen nedenleridir. Her iki mantar infeksiyonunun da mortalite oranları yüksektir. Özgün klinik bulgular göstermedikleri için risk faktörlerinin takibi, şüpheli olgularda uygun örneklerin alınması, en hızlı tanı yöntemlerinin kullanılması ve tedavinin erken başlanması hayati önem taşır. Bu yazıda "Amerika İnfeksiyon Hastalıkları Derneği (IDSA)", "Alman İnfeksiyon Hastalıkları Çalışma Grubu (AGIHO) ve Hematoloji-Onkoloji derneği (DGHO)", "Avrupa Lösemide İnfeksiyonlar Konferansı (ECIL)" ve "Avrupa Klinik Mikrobiyoloji ve İnfeksiyon Hastalıkları Derneği (ESCMID)" rehberleri ve uzman görüşleri gözden geçirilmiştir. Uygun tedavinin hasta ve merkezin özelliklerine göre belirlenmesi gerekir. Kandidemi tedavisi için nötropenik olmayan hastalarda belirli kriterlere göre kaspofungin, mikafungin, anidulafungin, vorikonazol veya lipozomal amfoterisin B (LAmB) önerilen primer ajanlardır. Nötropenik hastalarda kandidemi tedavisinde kaspofungin, mikafungin, anidulafungin veya LAmB kullanılması uygundur. İnvazif aspergillozisin (İA) primer tedavisinde vorikonazol önerilir. Posakonazol, LAmB veya kaspofungin İA’nın kurtarma tedavisi için antifungal ajanlardır. Ampirik tedavide kandidemi şüphesinde nötropenik olmayan hastalar için flukonazol, kaspofungin, anidulafungin veya mikafungin uygundur. Nötropenik hastalarda İA şüphesinde ampirik tedavi LFAmB, vorikonazol, mikafungin veya kaspofungin ile tavsiye edilir. Kandidiyazis riskindeki hastalar için proflaksi olarak risk faktörlerine göre flukonazol, posakonazol, vorikonazol veya ekinokandinler kullanılabilir. Primer hastalığa göre posakonazol, vorikonazol, itrakonazol, mikafungin veya kaspofungin İA için proflaktik olarak önerilir. Bu derlemenin amacı Kandida ve Aspergillus infeksiyonlarının tedavisinde temel yaklaşımları hatırlatmak, güncel kılavuzları inceleyerek yol haritalarının belirlenmesine yardımcı olmaktır.

TREATMENT OF NOSOCOMIAL CANDIDEMIA AND INVASIVE ASPERGILLOSIS: CURRENT APPROACHES

The management of invasive fungal infections (IFI) in immunosuppressive patients is a very important issue. Candida spp. and Aspergillus spp. are the most frequent causes of nosocomial IFIs. There are higher mortality rates in both of them. Due to there are no specific symptoms of IFIs, evaluating risk factors of those patients, taking appropriate samples in suspected cases, early diagnosis and prompt initiation of antifungal treatment are crucial behaviors for targeting satisfactory outcomes. In this article, we review "The Infectious Diseases Society of America (IDSA)", "The Infectious Diseases Working Party (AGIHO) and The German Society Hematology and Oncology (DGHO)", 'European Conference on Infections in Leukemia’ (ECIL) and "The European Society for Clinical Microbiology and Infectious Diseases (ESCMID)" guidelines and expert opinions. The appropriate treatment needs to be adjusted according to characteristics of patients and health care centers. Caspofungin, micafungin, anidulafungin, voriconazole or liposomal amphotericin B (LAmB) is the primary agents recommended for the treatment of candidemia in nonneutropenic patients according to specific criteria. Caspofungin, micafungin, anidulafungin or LAmB is the convenient agents for the management of neutropenic individuals, as well. Voriconazole is recommended for the treatment of invasive aspergillosis (IA). Besides posaconazole, LAmB or caspofungin is the antifungal agents for salvage treatment of IA. Empirical therapy for suspected candidemia in non-neutropenic patients, fluconazole, caspofungin, anidulafungin or micafungin is proper. Empirical therapy with an LFAmB, voriconazole, micafungin or caspofungin is recommended for suspected IA in neutropenic patients. As prophylaxis, fluconazole, posaconazole, voriconazole or echinocandins can be used for patients at risk of candidiasis according to the risk factors. According to primary disease posaconazole, voriconazole, itraconazole, micafungin or caspofungin is suggested as prophylaxis for IA. The goal of this review is to remind the main approaches for treatment of Candida and Aspergillus infections and to help determine a road map by searching current guidelines. 

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  • Arıkan Akdağlı S. İnvazif mantar infeksiyonlarının epidemiyolojisi: Nereden nereye? ANKEM Derg 2010;24(2):132- 134.
  • Demirkan F, Saydam G, Arda B, Ozcan MA. The management of invasive fungal infections: What to consider in empirical treatment? UHOD 2013;23(3):1-12.
  • Lass-Flörl C. The changing face of epidemiology of invasive fungal disease in Europe. Mycoses 2009;52(3):197-205.
  • Erol S. Hastane kaynaklı aspergilloz: Epidemiyoloji ve kontrol. Mikrobiyol Bul 2010; 44(2):323-338.
  • Kullberg BJ, Arendrup MC. Invasive Candidiasis. N Engl J Med 2015;373(15):1445-56.
  • ECIL5: Primer antifungal prophylaxis. http://www.kobe.fr/ ecil/telechargements2013/ECIL5antifungalprophylaxis.pdf erişim:12.11.2015.
  • 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. CID 2016; 62 (15 February):e1-e50.
  • Mousset S., Buchheidt D., Heinz W, et al. Treatment of invasive fungal infections in cancer patients-updated recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO), Ann Hematol. 2014; 93(1):13-32.
  • Cornely OA, Bassetti M, Calandra T, et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 2012; 18 (Suppl. 7): 19-37.
  • 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- 444.
  • Karthaus M. Prophylaxis and treatment of invasive aspergillosis with voriconazole, posaconazole and caspofungin– review of the lıterature. Eur J Med Res 2011;16(4):145-152.
  • Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin. Infec. Dis. 2008;46(3):327-60.
  • Patterson TF, Thompson CR, Denning DW, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. CID; 2016:63 (15 August): e1-e60.
  • Tacke D, Buchheidt D, Karthaus M, et al. Primary prophylaxis of invasive fungal infections in patients with haematologic malignancies. 2014 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol. 2014;93(9):1449-1456.