Lower Mortality Associated With Adjuvant Corticosteroid Therapy in Non-HIV-Infected Patients With Pneumocystis jirovecii Pneumonia: A Single-Institution Retrospective US Cohort Study

Abstract

Background Pneumocystis jirovecii pneumonia (PJP) remains a cause of mortality in HIV-negative patients. The clinical benefit of adjuvant corticosteroids in these patients is uncertain. This study aimed to determine if corticosteroids reduced mortality in a cohort of HIV-negative PJP patients. 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 mortality predictors. Results Common underlying conditions in HIV-negative patients were hematologic malignancies (28.6%), autoimmune disorders (25.9%), or solid organ transplantation (10.7%). HIV-negative patients had higher rates and duration of mechanical ventilation and ICU stay. Survival was significantly increased in HIV-negative patients receiving adjuvant corticosteroids, with 100% mortality in patients not receiving corticosteroids vs 60% mortality in patients receiving corticosteroids (p=0.034). In an adjusted multivariable model, no adjuvant corticosteroids use was associated with higher mortality (OR 13.5, 95% CI: 1.1-158.5, p= 0.039) regardless of HIV status. Conclusions We found substantial mortality among HIV-negative patients with PJP and adjuvant corticosteroid use was associated with decreased mortality. Response to corticosteroids is best established in HIV infected patients, but emerging reports suggest a similar beneficial response in PJP patients without HIV infection. Further prospective studies may establish a more definitive role of corticosteroid addition among HIV-negative patients with PJP.

A Clinically Applicable Nomogram for Predicting the Risk of Invasive Mechanical Ventilation in Pneumocystis jirovecii Pneumonia

“…It has been known that clinical characteristics of HIV-positive and HIV-negative PCP patients are markedly different. Overall, HIV-positive PCP patients tend to be younger and have higher oxygenation index, lower serum LDH, and lower blood urea nitrogen levels ( Mundo et al, 2020 ; Feng et al, 2021 ). Therefore, these variables, which reflect the severity of disease, can be confounding factors for AIDS/HIV infection in multivariate logistic regression analysis.…”

Pneumocystis jirovecii pneumonia: a proposed novel model of corticosteroid benefit

“…14 In addition, a subgroup analysis showed adjuvant corticosteroids associated with decreased mortality in a cohort of 28 HIV-negative patients with PJP. 15 We believe PJP pathogenesis in patients without or with HIV is similar in essential ways. Baseline immunosuppression sets the stage for PJP by permitting copious colonization of lungs with fungi (Figure 1, Box 1).…”

“… 14 In addition, a subgroup analysis showed adjuvant corticosteroids associated with decreased mortality in a cohort of 28 HIV-negative patients with PJP. 15 …”

Risk of infection associated with targeted therapies for solid organ and hematological malignancies

“…Most likely, the most relevant preventable infection is PJP in patients treated with glucocorticoids, a condition with a dismal prognosis in non-HIV patients. 100 Prophylaxis according to current recommendations should be considered. 9 …”