Previous corticosteroid exposure associates with an increased pneumonia mortality among HIV-negative patients: a global research network with a follow-up multicenter case-control study.

BACKGROUND

HIV-negative patients have substantial mortality from pneumonia (PJP). We lack predictors of HIV-negative PJP-associated mortality.

OBJECTIVE

We aim to characterize the role of prior corticosteroid exposure in PJP-related mortality.

METHODS

We queried a global research network to identify adult HIV-negative patients with PJP with or without corticosteroid exposure in the preceding year before diagnosis ( = 8,021). We performed a propensity score-matched analysis to adjust baseline patient characteristics and analyzed outcomes. We follow-up the results with a multicenter ten years retrospective case-control cohort of HIV-negative patients tested for PJP by PCP Direct Fluorescent Antigen. We used a Cox proportional hazards model for survival analysis.

RESULTS

1822 HIV-negative propensity-scored matched patients with prior corticosteroid exposure had significantly increased 10 weeks (16% 9%, p < 0.0001) and one-year mortality after PJP diagnosis (23% 14%,  < 0.0001). (1→3)-β-D-glucan (197.6 ± 155.8 63 ± 0 pg/ml,  = 0.014), ferritin levels (1227 ± 2486 768 ± 1060 mcg/l,  = 0.047), lymphopenia (1.5 ± 1.5 2.0 ± 1.6 10 cells/µl,  < 0.0001) and hypoxia (SatO: 86.7% 91.6%,  < 0.0001) were higher or worse in those with prior steroid use. Patients who died were more likely to have previously received dexamethasone (35% 16%,  < 0.001) or prednisone (49% 29%,  < 0.001). Adjusted Cox proportional-hazard model validation showed an independently increased mortality at 10 weeks (HR: 3.7, CI: 1.5-9.2,  = 0.004) and 1 year (HR: 4.5, CI: 2.0-10.4,  < 0.0001) among HIV-negative patients with previous corticosteroid exposure.

CONCLUSION

Preceding corticosteroids in HIV-negative patients with PJP are associated with higher mortality. A higher fungal burden may influence corticosteroid-mediated mortality. Assessment of PJP prophylaxis must become a standard clinical best practice when instituting corticosteroid therapy courses.