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

Lilian Vargas Barahona; Kyle C Molina; Laura C Pedraza-Arévalo; Stefan Sillau; Alex Tagawa; Sias Scherger; Daniel B Chastain; Leland Shapiro; Jose Tuells; Carlos Franco-Paredes; Kellie L Hawkins; James P Maloney; George R Thompson 3rd; Andrés F Henao-Martínez

doi:10.1177/20499361231159481

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

Ther Adv Infect Dis. 2023 Mar 14:10:20499361231159481. doi: 10.1177/20499361231159481. eCollection 2023 Jan-Dec.

Authors

Lilian Vargas Barahona¹, Kyle C Molina^{2

3}, Laura C Pedraza-Arévalo⁴, Stefan Sillau⁵, Alex Tagawa⁶, Sias Scherger², Daniel B Chastain⁷, Leland Shapiro^{2

8}, Jose Tuells⁹, Carlos Franco-Paredes¹⁰, Kellie L Hawkins^{2

11}, James P Maloney¹², George R Thompson 3rd¹³, Andrés F Henao-Martínez¹

Affiliations

¹ Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, 12700 E. 19th Avenue, Mail Stop B168, Aurora, CO 80045, USA.
² Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
³ Department of Pharmacy, University of Colorado Hospital, Aurora, CO, USA.
⁴ St. Barnabas Hospital, Bronx, NY, USA.
⁵ Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA.
⁶ Center for Gait and Movement Analysis (CGMA), Children's Hospital Colorado, Aurora, CO, USA.
⁷ Department of Clinical and Administrative Pharmacy, University of Georgia College of Pharmacy, Albany, GA, USA.
⁸ Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, CO, USA.
⁹ Department of Community Nursing, Preventive Medicine and Public Health and History of Science, University of Alicante, Alicante, Spain.
¹⁰ Hospital Infantil de México Federico Gómez, México City, México.
¹¹ Denver Health Medical Center, Denver, CO, USA.
¹² Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
¹³ Division of Infectious Diseases, University of California -Davis, Davis, CA, USA.

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.

Keywords: HIV-negative patients; Pneumocystis carinii; Pneumocystis jirovecii; corticosteroids; immunocompetent; mortality.