Successful management of histoplasmosis with novel triazole antifungals: a brief report

Standard therapy for histoplasmosis is often limited by drug-drug interactions, toxicity and variable pharmacokinetics. We report clinical experience using the novel triazoles posaconazole and isavuconazole as alternative treatment options.

A retrospective case series was conducted. We analysed six cases of confirmed histoplasmosis (identified by culture, histopathology or PCR) in patients hospitalized in Barcelona, Spain, between 2017 and 2022. Patients received posaconazole delayed-release tablets (300 mg daily) or isavuconazole capsules (200 mg daily) as primary or step-down therapy. Complete response was defined as the resolution of all attributable signs and symptoms with microbiological clearance and/or radiological improvement when available.

The cohort included immunocompromised and immunocompetent patients with disseminated (n = 3), localized (n = 2) and chronic cavitary pulmonary (n = 1) histoplasmosis. Comorbidities included HIV, chronic lymphocytic leukaemia and corticosteroid use. Novel triazoles were utilized as step-down therapy after liposomal amphotericin B (LAmB) induction (n = 5) or as primary oral therapy (n = 1) for a median duration of 11.75 months. One patient with severe intestinal involvement received isavuconazole following itraconazole-induced hepatotoxicity and short-course LAmB. All six patients (100%) achieved complete clinical, radiological and/or mycological response without evidence of toxicity or relapse during 1-5 years of follow-up.

These findings contribute real-world evidence supporting the potential role of posaconazole and isavuconazole as alternative therapeutic options for confirmed histoplasmosis given their favourable safety profile, long-term tolerability and clinical outcomes in our series. Larger multicentre comparative studies are needed to better define the role of novel triazoles compared with the current standard of care (itraconazole).