Breakthrough invasive fungal infection among patients with haematologic malignancies: A national, prospective, and multicentre study.

We describe the current epidemiology, causes, and outcomes of breakthrough invasive fungal infections (BtIFI) in patients with haematologic malignancies. BtIFI in patients with ≥ 7 days of prior antifungals were prospectively diagnosed (36 months across 13 Spanish hospitals) according to revised EORTC/MSG definitions. 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. 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.

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Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

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Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Pedro Puerta-Alcalde has received honoraria for talks on behalf of Merck Sharp and Dohme, Lilly, ViiV Healthcare and Gilead Science. Pedro Puerta-Alcalde has participated in advisory boards for Gilead Science. Lucrecia Yáñez has received honoraria for talks on behalf of Gilead, Kite, Merck Sharp and Dohme, Pfizer, Abbvie, Roche, Jannsen and Novartis a grant support from Janssen. Jesús Fortún has received honoraria for talks on behalf of Gilead Science, Pfizer, Merck Sharp and Dohme, and Astellas. Carlota Gudiol has received honoraria for lectures from Pfizer, Gilead and Merck Sharp and Dohme. Ana Alastruey-Izquierdo has received honoraria for educational talks on behalf of Pfizer and Gilead Science. Carolina Garcia-Vidal has received honoraria for talks on behalf of Gilead Science, Merck Sharp and Dohme, Pfizer, Jannsen, Novartis, Lilly and a grant support from Gilead Science and Merck Sharp and Dohme.