Shows diagnostic pitfalls in identifying Pneumocystis jirovecii pneumonia in non-HIV patients, suggesting a need for improved testing strategies.
Introduction Pneumocystis jirovecii pneumonia (PJP) is increasingly encountered in non-HIV immunocompromised patients, particularly those with thoracic malignancy, fibrotic interstitial lung disease (ILD), and corticosteroid exposure. Serum (1→3)-β-D-glucan (BDG), commonly measured using the Fungitell® assay, is a widely used adjunct test but exhibits reduced sensitivity in non-HIV populations. We present a fatal case of BDG-negative PJP misdiagnosed as radiation pneumonitis and hospital-acquired pneumonia (HCAP). Case Presentation A 76-year-old man with idiopathic pulmonary fibrosis, squamous cell lung carcinoma (post-stereotactic body radiation therapy), and prior lymphoma in remission presented with fever, cough, and hypoxia. Chest CT revealed new bilateral ground-glass opacities (GGOs) superimposed on fibrotic lung. Labs showed normal leukocyte count, low procalcitonin, and a negative viral panel. He was diagnosed with radiation pneumonitis and started on prednisone 30 mg BID. He also received 7 days of broad-spectrum antibiotics for presumed HCAP. During his initial admission, bronchoscopy retrieved thick brown secretions; bronchoalveolar lavage (BAL) samples were sent for bacterial cultures and Pneumocystis jirovecii PCR. Serum BDG, measured with the Fungitell® assay, was 35 pg/mL (negative, ≤59 pg/mL). The patient was discharged on a steroid taper. He re-presented within one week with worsening hypoxemia and increased oxygen requirements. Repeat CT showed rapid radiologic progression with multilobar GGOs and consolidation. A second serum BDG (Fungitell®) was 52 pg/mL—still below positivity threshold. BAL PCR from the initial admission was finalized as positive for P. jirovecii. Despite initiation of high-dose trimethoprim-sulfamethoxazole and adjunctive corticosteroids, the patient’s respiratory failure progressed and ultimately passed. Discussion This case illustrates the diagnostic complexity of diffuse lung injury in non-HIV hosts. While PCR is sensitive, it cannot differentiate colonization from infection. However, the patient’s failure to improve with corticosteroids (for pneumonitis) and antibiotics (for HCAP), alongside radiologic and clinical decline, supported active PJP. False-negative BDG results—especially in non-HIV patients—are well documented, with reported sensitivities as low as 60-70% (Del Corpo et al., 2020). Low fungal burden and limited alveolar permeability may explain persistently sub-threshold BDG levels. Conclusion Negative BDG does not exclude PJP in non-HIV hosts. In high-risk patients with fibrotic ILD and new diffuse opacities, early invasive testing and empiric treatment are critical—even with negative BDG. This abstract is funded by: None
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Alnabulsi et al. (2026) studied this question.
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