Antifungal Prophylaxis and Treatment of Breakthrough Invasive Fungal Diseases in High-Risk Hematology Patients: A Prospective Observational Multicenter Study.
Gökhan Metan, Ayşe Çiftçioğlu, Rabin Saba, Ayşegül Ulu Kılıç, Kevser Özdemir, Yasemin Çağ, Demet Kiper Ünal, Firdevs Aksoy, Hande Berk, Gürkan Mert, Özlem Güzel Tunçcan, Anıl Tombak, İlker İnanç Balkan, Sema Alp Çavuş, Bahar Kandemir, Birsen Mutlu, Ahmet Çağkan İnkaya, Leylagül Kaynar, Memiş Hilmi Atay, Fadime Ersoy Dursun, Güray Saydam, Yakup Ünsal, Simge Fidan Sarı, Hamdi Akan, Study group
Author Information
Gökhan Metan: Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Hacettepe Üniversitesi Tıp Fakültesi Hastanesi, İç Hastalıkları Binası, Enfeksiyon Hastalıkları Ve Klinik Mikrobiyoloji Anabilim Dalı, Sıhhıye, Ankara, Türkiye.
Ayşe Çiftçioğlu: Clinical Research Unit, Faculty of Medicine, Ankara University, Ankara, Türkiye.
Ayşegül Ulu Kılıç: Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Erciyes University, Kayseri, Türkiye.
Kevser Özdemir: Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Pamukkale University, Denizli, Türkiye.
Yasemin Çağ: Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Medeniyet University, Istanbul, Türkiye.
Demet Kiper Ünal: Department of Hematology, Faculty of Medicine, Ege University, İzmir, Türkiye.
Firdevs Aksoy: Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Türkiye.
Hande Berk: Department of Infectious Diseases and Clinical Microbiology, Antalya Research and Education Hospital, Medical Sciences University, Antalya, Türkiye.
Gürkan Mert: Department of Infectious Diseases and Clinical Microbiology, Gülhane Medical Academy, Ankara, Türkiye.
Özlem Güzel Tunçcan: Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Gazi University, Ankara, Türkiye.
Anıl Tombak: Department of Hematology, Faculty of Medicine, Mersin University, Mersin, Türkiye.
İlker İnanç Balkan: Department of Infectious Diseases and Clinical Microbiology, Cerrahpaşa Medical Faculty, Istanbul University-Cerrahpaşa, Istanbul, Türkiye.
Sema Alp Çavuş: Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Dokuz Eylül University, İzmir, Türkiye.
Bahar Kandemir: Department of Infectious Diseases and Clinical Microbiology, Necmettin Erbakan University, Konya, Türkiye.
Birsen Mutlu: Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Kocaeli University, Kocaeli, Türkiye.
Ahmet Çağkan İnkaya: Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Hacettepe Üniversitesi Tıp Fakültesi Hastanesi, İç Hastalıkları Binası, Enfeksiyon Hastalıkları Ve Klinik Mikrobiyoloji Anabilim Dalı, Sıhhıye, Ankara, Türkiye.
Leylagül Kaynar: Department of Hematology, Faculty of Medicine, Erciyes University, Kayseri, Türkiye.
Memiş Hilmi Atay: Department of Hematology, Faculty of Medicine, 19 Mayıs University, Samsun, Türkiye.
Fadime Ersoy Dursun: Department of Hematology, Faculty of Medicine, Medeniyet University, Istanbul, Türkiye.
Güray Saydam: Department of Hematology, Faculty of Medicine, Ege University, İzmir, Türkiye.
We aimed to investigate the approaches for antifungal prophylaxis (AFP) and antifungal treatment in breakthrough invasive fungal diseases (IFDs) under AFP in high-risk hematology patients. Patients ≥ 18-years who received chemotherapy for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) or a conditioning regimen for allogeneic hematopoietic stem cell transplantation (AHSCT) with a duration of neutropenia (< 500 cells/mm) ≥ 10 days were included in a prospective multicenter observational study. Patients were followed until one week after recovery from neutropenia, discharge from the hospital, or death, which comes first to define the success of AFP. A total of 230 patients were recruited from 18 centers in seven months. Posaconazole prophylaxis was used in 134 (44 of whom failed) and 96 patients received fluconazole (28 of whom failed). The survival rate at 12 weeks after the initiation of AFP was higher in patients with successful prophylaxis (96.2% vs 56.9%, p < 0.001). IFDs were diagnosed in 27 patients. Duration of neutropenia was the only risk factor (OR: 1.03; 95% CI: 1.004-1.053) for development of IFDs. The types of breakthrough IFDs were; possible IFD in 15 patients, probable invasive aspergillosis (IA) in 9 patients, proven IA in 2 patients; and proven mucormycosis in 1 patient. Voriconazole was the drug of choice in 16 patients (5 of whom failed). Liposomal amphotericin B was used in the treatment of 8 patients (4 of whom failed). Posaconazole was the most frequently prescribed AFP in AML patients with high compliance to international guidelines. Approximately, one-third of ALL patients and AHSCT recipients received off-label posaconazole prophylaxis.
