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

Abstract

Background: HIV-negative patients have substantial mortality from Pneumocystis jirovecii 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 ( n = 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% versus 9%, p < 0.0001) and one-year mortality after PJP diagnosis (23% versus 14%, p < 0.0001). (1→3)-β-D-glucan (197.6 ± 155.8 versus 63 ± 0 pg/ml, p = 0.014), ferritin levels (1227 ± 2486 versus 768 ± 1060 mcg/l, p = 0.047), lymphopenia (1.5 ± 1.5 versus 2.0 ± 1.6 103 cells/µl, p < 0.0001) and hypoxia (SatO2: 86.7% versus 91.6%, p < 0.0001) were higher or worse in those with prior steroid use. Patients who died were more likely to have previously received dexamethasone (35% versus 16%, p < 0.001) or prednisone (49% versus 29%, p < 0.001). Adjusted Cox proportional-hazard model validation showed an independently increased mortality at 10 weeks (HR: 3.7, CI: 1.5–9.2, p = 0.004) and 1 year (HR: 4.5, CI: 2.0–10.4, p < 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.

Glucocorticoids as a risk factor for infection and adverse outcomes in non‐HIV and non‐transplant patients with cryptococcal meningitis

“…22 Similar to other opportunistic fungal infections-specifically invasive pulmonary aspergillosis and Pneumocystis jirovecii pneumonia (PJP) -prior glucocorticoid exposure is also associated with increased mortality. 13,23 A recent meta-analysis linked glucocorticoid treatment with worse outcomes in invasive aspergillosis and PJP in patients without HIV, but the findings were equivocal in CM in PWH. 24 Previous glucocorticoid usage (OR: 2.40, 95% CI: 1.37-4.…”

“…It is not uncommon for NHNT patients to have a protracted course before presenting for care, which can lead to disseminated infection and multiorgan involvement 22 . Similar to other opportunistic fungal infections—specifically invasive pulmonary aspergillosis and Pneumocystis jirovecii pneumonia (PJP) —prior glucocorticoid exposure is also associated with increased mortality 13,23 . A recent meta‐analysis linked glucocorticoid treatment with worse outcomes in invasive aspergillosis and PJP in patients without HIV, but the findings were equivocal in CM in PWH 24 .…”

“…Our group has published several reports using the same database. [13][14][15] Each contributing healthcare organisation (HCO) enters the data collected from electronic medical record (EMR) systems to provide pa- System to protect patient healthcare data and satisfies the requirements of the HIPAA security rule.…”

“…Additionally, prior glucocorticoids may relate to worse outcomes in persons with opportunistic fungal infections among individuals without HIV. 13 We lack an understanding of the role of glucocorticoids as a risk factor for the onset of disease and for disease outcome in NHNT CM in NHNT individuals. Our study aims to characterise the clinical features associated with CM in NHNT individuals and outcomes based on prior glucocorticoid exposure.…”

“…In high‐resource settings where glucocorticoids are widely used and accessible, there may be an underestimation of their contribution to enhancing CM susceptibility in NHNT individuals. Additionally, prior glucocorticoids may relate to worse outcomes in persons with opportunistic fungal infections among individuals without HIV 13 . We lack an understanding of the role of glucocorticoids as a risk factor for the onset of disease and for disease outcome in NHNT CM in NHNT individuals.…”