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Background: Itraconazole is the treatment of choice for many fungal infections, including histoplasmosis. While the tolerability of itraconazole has been described in short-term trial settings, there are few studies on side effects during long-term therapy. Fluconazole, which is usually thought to be less toxic, is associated with 52% toxicity in long-term treatment., Objectives: To determine the frequency, types, and timing of side effects from itraconazole therapy, the resulting changes to treatment plans, and associations between patient characteristics and itraconazole serum levels with side effect status., Methods: We conducted a single-centre, retrospective study of adult patients with histoplasmosis receiving itraconazole therapy for at least 28 days from 2002 to 2021. Reported side effects were characterized, and propensity score matching was used to compare itraconazole serum levels between patients with and without side effects., Results: Sixty-three out of 227 (27.8%) patients experienced at least one side effect, the most common of which were hepatotoxicity (7.0%), nausea/vomiting (6.6%), and diarrhoea (6.2%). 12 (19.0%) patients with side effects underwent an itraconazole dose reduction and 29 (46.0%) had itraconazole discontinued. The median time to side effect was 45 days. Median itraconazole serum levels were significantly higher among patients with side effects than in a propensity score-matched population without side effects (2.9 versus 1.8 mcg/mL, P = 0.009)., Conclusions: Side effects were experienced by approximately one-quarter of patients with histoplasmosis receiving long-term itraconazole therapy. About two-thirds of these patients had a therapeutic intervention. Itraconazole resulted in a lower frequency of side effects than fluconazole, as measured in other studies., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Histoplasmosis is an important infection among transplant recipients. Few studies have described its epidemiology and outcomes in the modern era., Methods: We conducted a retrospective analysis using medical records from a single center in the United States. We included patients 18 years or older with histoplasmosis. We divided the cohort into transplant recipients and immunocompetent groups to assess the outcomes in both groups. We utilized Cox hazard models to assess 90-day all-cause mortality., Results: The study included 137 patients; with 28 (20%) transplant recipients. After the first year post-transplant, patients with lung transplant (30%) had a diagnosis of histoplasmosis. Transplant recipients exhibited a significantly higher incidence of disseminated histoplasmosis than immunocompetent patients (64% vs. 34%, p = 0.001), higher admission to ICU (39% vs. 16%; p = 0.01) and higher but not significant 90-day crude all-cause mortality (14% vs. 11%, p = 0.71). Patients with transplants had a higher, but not significant hazard of all-cause mortality at 90 days (hazard ratio: 1.5; 95% confidence interval: 0.4-3.9) when compared to immunocompetent patients., Conclusion: Transplant recipients were more commonly diagnosed with histoplasmosis after the first year post-transplantation, and although they exhibited a higher hazard for death at 90 days, this increase was not statistically significant., (© 2024 Wiley Periodicals LLC.)