Fungal colonization, emergence of resistant strains, and breakthrough invasive fungal infections during antifungal prophylaxis with micafungin in patients with leukaemia and stem cell transplant recipients. A retrospective single centre analysis

David Nachbaur*, Olga Angelova, Dorothea Orth, Adelheid Ditlbacher, Cornelia Lass-Floerl

Author address: 

Innsbruck, AT

Abstract: 

Objectives: Mould-active antifungal prophylaxis is increasingly used in patients who are at a very high risk for invasive fungal infections. Micafungin, a novel echinocandin, has been approved by the EMA for the prophylaxis and treatment of invasive candida infections in stem cell transplant recipients and patients with leukemia and prolonged neutropenia. 
Methods: Between June 2011 and June 2012 sixty-five patients with an anticipated duration of neutropenia of more than 7 days received 100 courses of primary antifungal prophylaxis with micafungin 50 mg i.v. once daily. The median number of days with micafungin prophylaxis was 14 (range, 2-48) starting on the first day of chemotherapy or when ANC counts dropped < 0.5 G/L. Underlying diseases were acute leukemia (75%), lymphoma (14%), myeloma (7%), myelodysplastic syndrome (3%) and severe aplastic anemia (1%). Treatment types were induction/consolidation and/or salvage chemotherapy courses (54%), stem cell transplantation (40%), and other types of chemotherapy (6%). 
Results: The incidence of proven and probable breakthrough invasive fungal infection according to the revised EORTC/MSG criteria were 6% (6/100) and 3% (3/100), respectively. There were two blood-stream infections caused by yeasts (C. krusei, Trichosporon asahii) and four IFIs caused by non-aspergillus moulds diagnosed by biopsy of either lung or skin lesions. Susceptibility patterns were only available only for the two yeasts showing micafungin-resistance only for the Trichosporon asahii isolate. The three cases of probable IFI were diagnosed by CT scan only. During 41 courses of prophylaxis with micafungin patients showed fungal colonization documented by weekly surveillance cultures from various body sites. Species diagnostic of 97 fungal isolates revealed C. spp. in 41 (42%), C. glabrata in 20 (21%), C. albicans in 17 (18%), C. krusei in 7 (7%), S. cerevisiae in 4 (4%), C. dubliniensis in 2 (2%), and C. famata, C. guilliermondii, C. haemullonii, C. parapsilosis, C. robusta, and Rhodotorula glutinis each in 1 (1% each). None of the isolates showed micafungin-resistance. 
Conclusions: These real-life data on micafungin as primary antifungal prophylaxis in adult patients with hematological malignancies at a very high risk for IFI demonstrate an acceptable low incidence of proven breakthrough IFI of only 6%. Emergence of micafungin-resistant Candida strains during prophylaxis was not observed. 

2013

Full conference title: 

Annual Meeting of European Society for Blood and Marrow Transplantation
    • EBMT 39th (2013)