1171 - Lower Mortality with Adjuvant Corticosteroid Therapy in non-HIV Infected Patients with pneumocystis jirovecii pneumonia: A Single US Cohort Study and a Proposed Novel Mechanism of Corticosteroids

Background: Pneumocystis jirovecii pneumonia (PJP) remains a cause of mortality in HIV-negative patients. The clinical benefit of adjuvant corticosteroids given at the time of PJP antimicrobial therapy in these patients is uncertain.  This study aimed to determine if corticosteroids reduced mortality in a cohort of HIV-negative PJP patients, and to propose a novel mechanism explaining corticosteroid benefit in patients regardless of HIV status.

Methods: We examined a retrospective case series of patients diagnosed with PJP at the University of Colorado Hospital between 1995-2019. Data were collected in 71 PJP-infected patients. Twenty-eight patients were HIV-negative, and 43 were infected with HIV. We performed bivariate and forward, stepwise multivariable logistic regressions to identify predictors of mortality.

Results: Underlying conditions in HIV-negative patients were hematologic malignancies (28.6%), autoimmune disorders (25.9%), or solid organ transplantation (10.7%). Compared to HIV-positive patients, HIV-negative patients had higher rates and duration of mechanical ventilation and ICU stay. Survival was significantly increased in HIV-negative patients receiving adjunct corticosteroids, with 100% mortality in patients not receiving corticosteroids vs 60% mortality in patients receiving corticosteroids (p=0.034). In an adjusted multivariable model, corticosteroids were associated with lower mortality (OR 13.5, 95% CI: 1.1-158.5, p= 0.039) regardless of HIV status. In a novel model of adjunct corticosteroid benefit, we propose corticosteroids reduce immune-mediated lysis of Pneumocystis organisms that curtails the surfactant-disabling effect of PJP internal contents.Table 1. Multivariable Analysis of Predictors of Mortality in patients with PJP
Figure 1. Mortality differences by HIV status and use of steroids in PJP


Conclusion: We found substantial mortality among HIV-negative patients with PJP and adjunct corticosteroid use was associated with decreased mortality. Adjunct corticosteroid mortality-lowering effect is best explained by suppressing pneumocystis lysis.  This reduces surfactant disruption resulting from pneumocystis internal substances.Figure 2. Proposed mechanism of action for benefits of adjunct exogenous corticosteroid therapy during PJP