Multisystem Lomentospora prolificans progression on fosmanogepix despite in vitro activity: a call for expanding clinical research on novel antifungals.

BACKGROUND

Lomentospora prolificans is a rare and often fatal cause of invasive mold disease (IMD), particularly in immunocompromised individuals. Treatment remains difficult due to intrinsic resistance to most antifungals and the challenges of achieving therapeutic drug levels in the central nervous system. Fosmanogepix and olorofim are novel antifungal agents with promising activity against difficult-to-treat molds, including L. prolificans, and show potential for excellent central nervous system penetration.

CASE SUMMARY: We report a case of disseminated L. prolificans infection with pulmonary, ocular, and central nervous system involvement in a 73-year-old man following haploidentical hematopoietic cell transplantation for peripheral T-cell lymphoma. Despite early neutrophil engraftment, the absence of graft-versus-host disease, and treatment with fosmanogepix, his infection progressed to fatal fungal meningitis.

CONCLUSION

This case underscores the limitations of relying on in vitro susceptibility results to predict clinical response in the absence of clinical breakpoints, particularly in deep-seated infections where drug penetration may be limited. While prior case reports have described successful outcomes with novel agents, publication bias may overrepresent favorable results. This case supports the urgent need for rigorous evaluation of emerging antifungal therapies in real-world settings.