El Kurdi, Rawan

Abstract Early diagnosis and treatment are essential for improving outcomes of coccidioidal meningitis. While the detection of IgG by serologic testing of the cerebrospinal fluid (CSF) has been a mainstay of diagnosis for years, the diagnosis of coccidioidal meningitis in clinical practice can be very challenging due to suboptimal sensitivity of laboratory tests. We reviewed the results of the CSF diagnostic test results from the initial lumbar puncture in 110 patients with proven, probable, and likely coccidioidal meningitis from 1989 to 2024. One hundred four patients were diagnosed with coccidioidal meningitis on the initial CSF examination. The positivity rate of the first CSF testing was 89.1% (n = 64) for IgG by enzyme immunoassay, 62.2% (n = 98) for IgG by immunodiffusion, and 70.2% (n = 104) for IgG by complement fixation, 4.4% (n = 90) for fungal culture, 18.8% (n = 69) for polymerase chain reaction, and 33% (n = 21) for Coccidioides antigen. The non-specific fungal marker 1,3-β-d-glucan was positive in the CSF in 70.4% (n = 27) of samples. Contrasted brain magnetic resonance imaging identified leptomeningeal enhancement in 53.1%. Optimal detection of coccidioidal meningitis requires a combination of diagnostic modalities.

Abstract Coccidioidomycosis is an endemic fungal infection caused by the soil-dwelling Coccidioides. One prior study showed that persons with diabetes mellitus (DM) with elevated glucose at the time of coccidioidomycosis had poorer coccidioidal outcomes compared to persons without DM. We aimed to assess the association between hemoglobin A1C (A1C) and outcomes among persons with coccidioidomycosis and coexisting DM. We conducted a retrospective case-control study of patients with DM (cases) and without DM (controls) with coccidioidomycosis to assess the effect of glycemic control on outcomes in patients with DM. From January 1, 2017, to October 13, 2022, we identified 138 DM patients with coccidioidomycosis and compared them with 283 non-DM control patients with coccidioidomycosis. Compared with controls, cases were more likely to require hospitalization (OR 1.20, P < .001), have a lung cavity (OR 1.36, P < .001) and cavitary complications (OR 1.09, P = .001), require surgical management (OR 1.07, P = .016), and experience relapsed infection (OR 1.09, P = .041). Among the cases, when baseline A1C was assessed as a continuous variable, each 1-unit increase of A1C had a significant effect on coccidioidomycosis-related hospitalizations (A1C OR 1.59, P = .005) and the presence of cavities (OR 1.42, P = .01). Controlling for Charlson Comorbidity Index did not change the significance of A1C influence on outcomes of hospitalization and lung cavities. DM patients with A1C levels ≤8.0 at presentation did not have increased adverse coccidioidomycosis outcomes. In summary, glycemic control profoundly impacts the outcomes of diabetic patients with coccidioidomycosis.

Abstract Coccidioidomycosis can cause severe meningitis, requiring lifelong treatment. In this study, we sought to better understand the potential effect of pharmacogenomic testing on treatment outcomes of patients with coccidioidal meningitis. Of 13 patients with coccidioidal meningitis who underwent pharmacogenomic testing, 11 had genetic variants of CYP2C19 and CYP3A5 that affect antifungal efficacy. These results led to real-time treatment changes and future antifungal planning. Routine pharmacogenomic testing helps to avoid antifungal treatments that are futile or lead to adverse effects.