Treatment and outcome of chronic disseminated candidiasis in the era of antifungal prophylaxis: a retrospective multicentre cohort of 111 patients

Abstract

Summary Background Chronic disseminated candidiasis (CDC) is a severe manifestation of invasive candidiasis predominantly affecting patients with haematological malignancies. Treatment recommendations are based on limited observational data, and the impact of widespread antifungal prophylaxis on CDC epidemiology and outcomes remains poorly characterised. We aimed to comprehensively characterise CDC and explore associations between antifungal treatment strategies and clinical outcomes. Methods We performed a retrospective, multinational cohort study including adults with possible, probable, or proven CDC diagnosed between 2007 and 2025 identified through the FungiScope® registry (ClinicalTrials.gov: NCT01731353) and collaborating networks in 19 countries. Diagnostic findings, treatment strategies, and outcomes were analysed over 12 months. Exploratory comparative analyses assessed the association between antifungal treatment strategies and treatment response (composite of clinical, radiological, and mycological findings) and overall survival using inverse probability of treatment weighting to account for the time-varying confounders neutropenia and corticosteroid exposure. Findings Of 111 patients, CDC was classified as possible in 23.4% (n = 26), probable in 50.5% (n = 56), and proven in 26.1% (n = 29) of patients. The predominant species were Candida albicans (32.4%, n = 36) and Candida tropicalis (24.3%, n = 27); no species was identified in 30.6% (n = 34). Breakthrough CDC occurred in 24.8% (27/109) of patients. PET/CT was used in 26.1% (n = 29) of patients for follow-up. Caspofungin (36.9%, 41/111) and liposomal amphotericin B (23/111; 20.7%) were the most frequently first-line agents for antifungal treatment. No statistically significant associations were detected between first-to-second-line treatment strategy, azole selection, and treatment response. Median treatment duration was 107 days (IQR 49–182), and no CDC relapse occurred after discontinuation. Corticosteroids for immune reconstitution inflammatory syndrome were used in 4.5% of patients. All-cause mortality was 33.3% (37/111), CDC-attributable mortality was 4.5% (5/111). Overall survival was higher among patients with breakthrough CDC than without (88.9% vs 58.5%; p = 0.004). Interpretation No statistically significant associations between antifungal treatment strategy and treatment response or survival were detected in this retrospective dataset. However, the comparative treatment analyses were exploratory and the study was not powered to exclude clinically meaningful differences between antifungal strategies. Median treatment duration was shorter than previously reported. Future prospective studies integrating immunological biomarkers and the use of PET/CT-guided strategies are needed to optimise individualised treatment decision-making. Funding This study received no dedicated external funding. FungiScope® receives unrestricted grants for registry maintenance and infrastructure from Basilea Pharmaceutica, Melinta Therapeutics LLC, Mundipharma Ltd., and Pfizer Inc, which had no role in the study design, conduct analysis, interpretation, manuscript preparation, or the decision to submit for publication.