P-1954. Clinical, Laboratory, and Biomarker Predictors of 90-Day Mortality in Non-HIV, Non-Transplant Pneumocystis Pneumonia

TL;DR

This study identifies clinical and biomarker predictors of 90-day mortality in non-HIV, non-transplant patients with Pneumocystis pneumonia.

Contribution

The study provides novel insights into mortality risk factors for PJP in a non-HIV, non-transplant population using a large federated database.

Findings

Non-survivors had higher 90-day mortality rates, older age, and more comorbidities.

Lower lymphocyte counts and higher serum BDG were associated with increased mortality.

Inflammation markers like CRP did not show significant differences between survivors and non-survivors.

Abstract

Pneumocystis jirovecii pneumonia (PJP) poses a growing threat in immunocompromised, non-HIV, non-transplant (NHNT) adults. Clinical features and pathogenesis associated with mortality are poorly characterized. This study explores clinical features and biomarkers reflecting immunologic capacity, inflammation, and pathogen load associated with NHNT PJP 90-day mortality.updaTable 1.Clinical features of NHNT PJP patients by 90-day mortalityFigure 1.Selected biomarkers in NHNT PJP patients by 90-day mortality

Clinical features of NHNT PJP patients by 90-day mortality

Selected biomarkers in NHNT PJP patients by 90-day mortality

This retrospective cohort study (2011-2024) used TriNetX, a federated database of anonymized electronic health records. We selected adults with PJP (positive PCR orβ-D-glucan [BDG] results from respiratory samples) who had neither HIV nor history of solid organ transplantation. We compared demographics, comorbidities, immunosuppressant use, and laboratory biomarkers in survivors and non-survivors. Cox regression analysis was used to assess 90-day mortality differences.

In 578 NHNT patients with PJP, 90-day mortality was 29.4%. Non-survivors were significantly older (mean 64.4 ± 14.1 vs 57.2 ± 19.1 years, p< 0.001) and had a higher Charlson comorbidity index (mean 5.9 ± 3.9 vs 5.2 ± 3.8, p=0.035), with increased prevalence of liver disease (mean 14.7% vs 7.7%, p=0.010) and heart failure (mean 37.1% vs 27.0%, p=0.017) (Table 1). Laboratory findings showed lower lymphocyte counts (23.6 ± 77.3 vs 231.0 ± 609.5 µL-1, p=0.009), hemoglobin (9.8 vs 10.6 g/dL, p< 0.001), and platelets (157.4 vs 227.0 x 103/µL, p< 0.001) in non-survivors. Elevated total bilirubin was also associated with mortality (2.5 vs 0.8 mg/dL, p< 0.001). Scatter plots by unadjusted Cox regression showed higher serum BDG (300 vs 200 pcg/mL, HR: 20.2 p=0.018) and ferritin (1901.9 vs 1158.5 ng/mL, HR: 1.0, p=0.025) in non-survivors. In contrast, other acute phase reactants fibrinogen and C-reactive protein (CRP) had no significant differences (Figure 1).

In NHNT adults with PJP, 90-day mortality was significantly associated with older age and organ dysfunction. As expected, evidence of immune dysfunction (absolute lymphocyte count) or a biomarker of fungal burden (serum BDG) predicted mortality, and no association with indicators of inflammation (CRP) was detected. Clinicians should prioritize early identification and management of high-risk patients and pursue a model-based approach to NHNT PJP therapeutics.

George R. Thompson III, MD, Astellas: Advisor/Consultant|Astellas: Grant/Research Support|Basilea: Advisor/Consultant|Basilea: Grant/Research Support|Cidara: Advisor/Consultant|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|GSK: Advisor/Consultant|GSK: Grant/Research Support|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support Andrés F. Henao Martínez, MD, MPH, F2: Grant/Research Support|Scynexis: Grant/Research Support

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