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00925njm 22002777a 4500 dc Puerta-Alcalde, Pedro author Monzó-Gallo, Patricia author Aguilar-Guisado, Manuela author Ramos, Juan Carlos author Laporte-Amargós, Júlia author Machado, Marina author Martín-Dávila, Pilar author Franch-Sarto, Mireia author Sanchez-Romero, Isabel author Badiola, Jon author Gómez, Lucia author Ruiz-Camps, Isabel author Yáñez, Lucrecia author Vázquez, Lourdes author Chumbita, Mariana author Marco, Francesc author Soriano, Alex author González, Pedro author Fernández-Cruz, Ana author Batlle, Montserrat author Fortún, Jesús author Guinea, Jesús author Gudiol, Carlota author García, Julio author Ruiz Pérez de Pipaón, Maite author Alastruey-Izquierdo, Ana author Garcia-Vidal, Carolina author 2023-07 Objectives: We describe the current epidemiology, causes, and outcomes of breakthrough invasive fungal infections (BtIFI) in patients with haematologic malignancies. Methods: BtIFI in patients with ≥ 7 days of prior antifungals were prospectively diagnosed (36 months across 13 Spanish hospitals) according to revised EORTC/MSG definitions. Results: 121 episodes of BtIFI were documented, of which 41 (33.9%) were proven; 53 (43.8%), probable; and 27 (22.3%), possible. The most frequent prior antifungals included posaconazole (32.2%), echinocandins (28.9%) and fluconazole (24.8%)-mainly for primary prophylaxis (81%). The most common haematologic malignancy was acute leukaemia (64.5%), and 59 (48.8%) patients had undergone a hematopoietic stem-cell transplantation. Invasive aspergillosis, principally caused by non-fumigatus Aspergillus, was the most frequent BtIFI with 55 (45.5%) episodes recorded, followed by candidemia (23, 19%), mucormycosis (7, 5.8%), other moulds (6, 5%) and other yeasts (5, 4.1%). Azole resistance/non-susceptibility was commonly found. Prior antifungal therapy widely determined BtIFI epidemiology. The most common cause of BtIFI in proven and probable cases was the lack of activity of the prior antifungal (63, 67.0%). At diagnosis, antifungal therapy was mostly changed (90.9%), mainly to liposomal amphotericin-B (48.8%). Overall, 100-day mortality was 47.1%; BtIFI was either the cause or an essential contributing factor to death in 61.4% of cases. Conclusions: BtIFI are mainly caused by non-fumigatus Aspergillus, non-albicans Candida, Mucorales and other rare species of mould and yeast. Prior antifungals determine the epidemiology of BtIFI. The exceedingly high mortality due to BtIFI warrants an aggressive diagnostic approach and early initiation of broad-spectrum antifungals different than those previously used. J Infect. 2023 Jul;87(1):46-53. 10.1016/j.jinf.2023.05.005 1532-2742 The Journal of infection 37201859 http://hdl.handle.net/20.500.12105/16163 Antifungal Breakthrough Fungal disease Invasive fungal infection Mortality Breakthrough invasive fungal infection among patients with haematologic malignancies: A national, prospective, and multicentre study