Opportunistic fungal infection risk and mortality in non-HIV, non-transplant US adults receiving systemic glucocorticoids: An observational cohort study.

The dose-dependent risk of opportunistic fungal infections and associated mortality from systemic glucocorticoids remains poorly defined in non-HIV, non-transplant (NHNT) populations. This study evaluated the cumulative incidence of opportunistic fungal infections and the association between glucocorticoid dose, infection risk, and 1-year mortality in NHNT adults. In this observational cohort study (NCT05707156), adults without HIV or solid organ transplants who received systemic glucocorticoids for ≥14 days between 2022 and 2024 were identified using the TriNetX research network. Glucocorticoid doses, standardized to prednisone equivalents (PEQ), were categorized as ≤10 mg/day, 11-20 mg/day, and >20 mg/day based on clinically relevant thresholds. Cumulative duration beyond the initial ≥14 days was unavailable. Multivariable logistic regression identified predictors of opportunistic fungal infections. Cox proportional hazards and Kaplan-Meier analyses evaluated associations between glucocorticoid dose and 1-year all-cause mortality. Among 7839 patients, 6% developed opportunistic fungal infections, predominantly histoplasmosis (96%). Compared with ≤10 mg/day, neither 11-20 mg/day (OR 0.85, 95% CI 0.18-3.91) nor >20 mg/day (OR 0.89, 95% CI 0.24-3.33) was independently associated with infection risk. Crude 1-year mortality was higher in the >20 mg group (1.1%) versus ≤10 mg (0.5%) and 11-20 mg (0.4%) groups (P = .002), but glucocorticoid dose was not independently associated with mortality after adjustment. Increased mortality was associated with older age (HR 1.03/year), female sex (HR 1.96), and higher Charlson Comorbidity Index (HR 1.17 per point). Higher glucocorticoid doses did not independently predict opportunistic fungal infection risk or mortality, illustrating the limitations of dose-based risk stratification.