Evaluating the clinical utility of Aspergillus, Mucorales, and Nocardia bronchoalveolar PCRs for the diagnosis of invasive pulmonary infections in patients with hematological malignancies.

Abstract

Invasive pulmonary infections are a significant cause of morbidity and mortality in patients with hematological malignancies and hematopoietic stem cell transplantation (HCT) recipients. A delay in identifying a causative agent may result in late initiation of appropriate treatment and adverse clinical outcomes. We examine the diagnostic utility of PCR-based assays in evaluating invasive pulmonary infections from bronchoalveolar lavage (BAL). Patients with hematological malignancies and HCT recipients who underwent bronchoscopy with BAL from January 2020 to January 2024 for unexplained pulmonary infiltrates and had ≥1 PCR targeting Aspergillus, Mucorales, or Nocardia (Eurofins-Viracor, KS) were reviewed. Testing for microbiology and pathology except BAL PCRs to identify the etiology of pulmonary infiltrate was defined as standard-of-care. Invasive fungal diseases were defined as per European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) 2020 guidelines. Pulmonary nocardiosis was defined by a combination of clinical, radiographic, and microbiologic criteria. Of 134 patients, 77 were HCT recipients, and 70% were on antifungal agents. Thirty-two were diagnosed with infection with one of the three target pathogens, including 20 with probable or proven invasive pulmonary aspergillosis (IPA), seven with mucormycosis, and three with nocardiosis. For IPA, 19 were diagnosed by standard-of-care, and one (5%) was solely diagnosed by Aspergillus PCR. Mucorales PCR was positive in three of seven cases of proven mucormycosis, but the cultures were negative in all. All three nocardiosis cases were detected by PCR and culture. In our cohort, PCR targeting Mucorales and Nocardia can improve the early detection of invasive pulmonary infection, whereas Aspergillus PCR has a low added value when done in conjunction with standard-of-care, including BAL galactomannan.IMPORTANCEInvasive pulmonary infections are a significant cause of morbidity and mortality in immunocompromised patients. Timely diagnosis of invasive pulmonary infection reduces the time to targeted treatment initiation and improves clinical outcomes. The recent European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) update included the addition of serum or bronchoalveolar lavage (BAL) PCR as a method to determine probable Aspergillus disease. This reflects an increased utilization of PCR-based assays in the diagnosis of fungal diseases. Although PCR assays for Aspergillus diagnosis have been well characterized in the literature, their additive clinical utility in conjunction with BAL galactomannan index measurements remains unclear. Moreover, only a few reports characterize the analytic and clinical performance of Mucorales and Nocardia PCR.