İnvaziv ve Dirençli Mantar Enfeksiyonlarında Fosmanogepix'in Klinik Etkinliği ve Güvenliği: Sistematik Bir Derleme

Özet (abstract)

Background: Fosmanogepix is a first-in-class Gwt1 inhibitor with oral and intravenous formulations and broad in vitro activity, but its clinical evidence is scattered across small trials and case reports. We reviewed all identifiable human data from the searched sources on its efficacy and safety in serious fungal infections. Methods: PubMed, Google Scholar, ClinicalTrials.gov, congress supplements, and citation lists were searched for publications available up to 1 September 2026. Any report of fosmanogepix given for a fungal infection with a reported outcome was eligible. Quality was appraised with JBI checklists, findings were synthesised narratively and stratified by study design, certainty was rated for each indication with a GRADE-informed approach, and scenario analyses explored patient duplication and reporting bias. Results: Thirty studies (34 reports) describing approximately 223 reported patient-episodes (an estimated 171 to 214 unique patients under duplication scenarios) were included: three phase 2 trials (n = 51), seven expanded-access or cohort series (n = 151) and 20 case-level reports (n = 21). Adjudicated treatment success was 16/20 (80%) in candidaemia and 8/9 (89%) in Candida auris candidaemia; in refractory invasive mould disease, global response was 8/20 (40%) with 25% Day-42 mortality. Physician-assessed favourable responses were 13/17 (76%) and 4/7 (57%) in aspergillosis, 38/50 (76%) and 26/32 (81%) in fusariosis, 7/11 (64%) in mucormycosis, and 8/11 (73%) in coccidioidomycosis. Of 21 individually described patients, 17 were alive at last report. Gastrointestinal intolerance was the main adverse effect, with drug-related discontinuation in 3/21 mould-disease trial participants. GRADE-informed certainty was low for candidaemia other than C. auris candidaemia and for refractory mould disease, and very low for every other indication. Conclusions: Uncontrolled data provide signals of activity, not evidence of comparative effectiveness, in candidaemia, including C. auris, and in fusariosis and other resistant mould infections, with acceptable tolerability during prolonged use. Small samples, absent comparators, overlapping cohorts, and probable publication bias limit the evidence.

Yazarların özeti; kaynağından alınmıştır. Journal of Fungi, 2026 · DOI ↗