TY - JOUR
T1 - Invasive fusariosis in patients with leukaemia in the era of mould-active azoles
T2 - increasing incidence, frequent breakthrough infections and lack of improved outcomes
AU - Matsuo, Takahiro
AU - Wurster, Sebastian
AU - Jiang, Ying
AU - Sasaki, Koji
AU - Tarrand, Jeffrey
AU - Lewis, Russell E.
AU - Kontoyiannis, Dimitrios P.
N1 - Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved.
PY - 2024/2/1
Y1 - 2024/2/1
N2 - Objectives: Historically, patients with leukaemia and invasive fusariosis (IF) have experienced poor outcomes in the setting of persistent immunosuppression. Herein, we retrospectively reviewed the incidence, presentation and outcomes of IF that are scarcely studied in contemporary cohorts of leukaemia patients. Methods: We identified adult leukaemia patients with proven or probable IF at MD Anderson Cancer Center during 2009–21. Independent risk factors for 42 day mortality after IF diagnosis were determined using a multivariable logistic regression model. Combined with historical data, the annual IF incidence density over the past 23 years was estimated using Poisson regression analysis. Results: Among 140 leukaemia patients with IF (114 proven), 118 patients (84%) had relapsed/refractory leukaemia and 124 (89%) had neutropenia at IF diagnosis. One hundred patients (71%) had pulmonary IF, 88 (63%) had disseminated IF and 48 (34%) had fungaemia. Coinfections were common (55%). Eighty-nine patients (64%) had breakthrough IF to mould-active triazoles. Most patients (84%) received combination antifungal therapy. Neutrophil recovery [adjusted OR (aOR), 0.04; 95% CI, 0.01–0.14; P< 0.0001], pulmonary IF (aOR, 3.28; 95% CI, 1.11–9.70; P= 0.032) and high SOFA score (aOR, 1.91 per 1-point increase; 95% CI, 1.47–2.50; P< 0.0001) were independent predictors of 42 day mortality outcomes. From 1998 to 2021, IF incidence density increased significantly at an annual ratio of 1.03 (95% CI, 1.01–1.06; P= 0.04). Conclusions: IF is predominantly seen in patients with relapsed/refractory leukaemia and increasingly seen as a breakthrough infection to mould-active triazoles. Despite frequent combination antifungal therapy, high mortality rates have persisted in patients with lasting neutropenia.
AB - Objectives: Historically, patients with leukaemia and invasive fusariosis (IF) have experienced poor outcomes in the setting of persistent immunosuppression. Herein, we retrospectively reviewed the incidence, presentation and outcomes of IF that are scarcely studied in contemporary cohorts of leukaemia patients. Methods: We identified adult leukaemia patients with proven or probable IF at MD Anderson Cancer Center during 2009–21. Independent risk factors for 42 day mortality after IF diagnosis were determined using a multivariable logistic regression model. Combined with historical data, the annual IF incidence density over the past 23 years was estimated using Poisson regression analysis. Results: Among 140 leukaemia patients with IF (114 proven), 118 patients (84%) had relapsed/refractory leukaemia and 124 (89%) had neutropenia at IF diagnosis. One hundred patients (71%) had pulmonary IF, 88 (63%) had disseminated IF and 48 (34%) had fungaemia. Coinfections were common (55%). Eighty-nine patients (64%) had breakthrough IF to mould-active triazoles. Most patients (84%) received combination antifungal therapy. Neutrophil recovery [adjusted OR (aOR), 0.04; 95% CI, 0.01–0.14; P< 0.0001], pulmonary IF (aOR, 3.28; 95% CI, 1.11–9.70; P= 0.032) and high SOFA score (aOR, 1.91 per 1-point increase; 95% CI, 1.47–2.50; P< 0.0001) were independent predictors of 42 day mortality outcomes. From 1998 to 2021, IF incidence density increased significantly at an annual ratio of 1.03 (95% CI, 1.01–1.06; P= 0.04). Conclusions: IF is predominantly seen in patients with relapsed/refractory leukaemia and increasingly seen as a breakthrough infection to mould-active triazoles. Despite frequent combination antifungal therapy, high mortality rates have persisted in patients with lasting neutropenia.
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U2 - 10.1093/jac/dkad377
DO - 10.1093/jac/dkad377
M3 - Article
C2 - 38073151
AN - SCOPUS:85184039170
SN - 0305-7453
VL - 79
SP - 297
EP - 306
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
IS - 2
ER -