Fluconazole Prophylaxis Significantly Reduce High Risk Invasive Fungal Infection in Immunocompromised Patients Stratified By a Risk Prediction Model

Abstract: Background: Patients on immunosuppressive drugs or those who are critically ill are at high risk for invasive fungal infections (IFIs). The assessment of IFI risk and the initiation of prophylaxis in these patients remain unclear. Methods: A Nomogram model was developed to evaluate humoral and cellular immune indicators in relation to IFI risk. High-risk patients, as identified by the model, were selected for a prospective, randomized study to assess the efficacy and safety of fluconazole prophylaxis. Patients deemed high risk received either fluconazole prophylaxis or a placebo until IFI occurrence or risk downgrade for up to 90 days. We compared the incidence of IFI and mortality during treatment between the two groups. Results: The Nomogram, created from a training cohort (n=384), included age, IgG level, and CD4+ cells count as predictive indicators of IFI, was validated in a separate cohort (n=281) with an area under the curve of 0.723. A total of 266 patients were recruited for the prospective study, with 158 high-risk patients randomly assigned to receive either fluconazole (n=78) or a placebo (n=80). Proven or probable IFI was reported in 8 patients in the fluconazole group and 39 patients in the placebo group (p=0.00). High risk IFI could be reduced to the low risk level with fluconazole prophylaxis. There was no significant difference in survival between the fluconazole and placebo groups (P=0.34). Adverse events potentially related to treatment were reported by 4 patients (4.9%) in the fluconazole group. Conclusions: This nomogram model effectively and reliably predicts the risk of IFI in immunocompromised patients. Fluconazole prophylaxis significantly reduces the incidence of IFI, particularly yeast infections, and may help to prevent fungal colonization. (ChiCTR2400079810.)