P-1098. Clinical outcomes in four patients with refractory Coccidioidal meningitis treated with olorofim

Abstract Background Coccidioidal meningitis (CM) remains a highly morbid condition. Olorofim is a novel agent that inhibits the fungal dihydroorotate dehydrogenase enzyme and has potent in vitro activity against Coccidioidomycosis. Demographics of patients at the time of olorofim initiation with description of prior treatments. Methods We performed a retrospective case series of 4 patients with refractory CM treated with olorofim between 2020 and 2024 comparing outcomes assessed by symptoms, brain imaging, and Mycosis Study Group (MSG) score. Change in Symptoms, MRI Brain Imaging, MSG Score, and CSF Parameters after Olorofim Initiation. Abbreviations: CF, Coccidiodes complement fixation; CSF, cerebrospinal fluid; MRI, magnetic resonance imaging, MSG, Mycosis Study Group (MSG). Results At baseline, mean age was 53 (range 41-66), mean time since diagnosis 950 days (range 378-1591), mean MSG score 5.8 (range 3-11), and mean azoles failed 3.25 (range 2-4). Follow-up occurred at variable intervals for a total duration of 332-985 days on therapy. In early follow-up, symptoms were improved in 3 patients and stable in 1; available imaging was improved in 2 patients and stable in 1; mean MSG score was 4.75, decreased in 1 patient, unchanged in 1, and increased but low in 2. In late follow-up, symptoms were improved in 3 patients and stable in 1; available imaging was improved in 1 patient and stable in 1; mean MSG score was 2.7, decreased in 2 patients, unchanged in 1, and increased in 1. Patient 3 developed significant transaminitis requiring dose reduction at day 91 with subsequent relapse (MSG score 14) but was eventually stabilized on combination therapy with fluconazole. Cerebral spinal fluid (CSF) complement fixation, glucose, protein and white blood cell count (WBC) graphed over time on antifungal treatment. Time 0 represents initiation of olorofim. Conclusion At last follow-up, 2 patients were doing well with improvement or stability in all domains, 1 patient died of unrelated causes, and 1 patient had late treatment failure after prolonged stability for 2.5 years. Olorofim may be an effective alternative treatment for patients with refractory CM. Mycosis Study Group (MSG) scores plotted over time. The plot excludes an MSG score of 14 for patient 3 shortly after Early follow-up period during a temporary hold on olorofim administration due to medication induced transaminitis. Disclosures All Authors: No reported disclosures