Microbiologic Diagnostic Workup of Acute Respiratory Failure with Pulmonary Infiltrates after Allogeneic Hematopoietic Stem Cell Transplantation: Findings in the Era of Molecular- and Biomarker-Based Assays

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) recipients frequently develop acute respiratory failure (ARF) with pulmonary infiltrates. Molecular- and biomarker-based assays enhance pathogen detection, but data on their yield in this population are scarce. This was a retrospective single-center study of 156 consecutive HSCT recipients admitted to the intensive care unit (ICU) between May 2013 and July 2017. Findings from a microbiologic diagnostic workup using currently available methods on bronchoalveolar lavage (BAL) and blood samples from 66 patients (age, 58 years [range, 45 to 64]; HSCT to ICU, 176 days [range, 85 to 407]) with ARF and pulmonary infiltrates were analyzed. In 47 patients (71%) a causative pathogen was identified (fungal, n = 28; viral, n = 26; bacterial, n = 18). Polymicrobial findings involving several pathogen groups occurred in 20 patients (30%). Culture (12/16, 75%), galactomannan (13/15, 87%), and Aspergillus-PCR (8/9, 89%) from BAL but not serum galactomannan (6/14, 43%) helped to diagnose invasive aspergillosis (n = 16, 24%). Aspergillus-PCR detected azole resistance in 2 cases. Mucorales was found in 7 patients (11%; BAL culture, n = 6; Mucorales-PCR, n = 1). Patients with identified pathogens had higher Simplified Acute Physiology Score II scores (P = .049) and inferior ICU survival (6% versus 37%, P < .01), which largely related to the presence of an invasive fungal infection. Eight patients (12%) had 1 or more viruses with uncertain lung pathogenicity as the sole microbiologic finding. A diagnostic microbiologic workup incorporating molecular- and biomarker-based assays identified pathogens in most HSCT recipients with ARF and pulmonary infiltrates admitted to the ICU. Implications of polymicrobial infection and pathogen patterns in these patients warrant further investigation.

Keywords: Acute respiratory failure; HSCT; Hematopoietic stem cell transplantation; ICU; Intensive care unit.

Figure 1

Patient flowchart.

Figure 2

Pathogen distribution among patients. Numbers of patients according to pathogen distribution are plotted against the horizontal axis. The following pathogens were observed in each group: Fungal + Bacterial + Viral: Talaromyces (n = 1), Aspergillus (n = 4), Stenotrophomonas (n = 3), Pseudomonas (n = 1), Escherichia coli (n = 1), CMV (n = 4), parainfluenza virus (n = 1); Fungal + Viral: Aspergillus (n = 4), Mucorales (n = 3), pneumocystis (n = 2), CMV (n = 5), influenza (n = 1), human metapneumovirus (n = 1); Fungal + Bacterial: Aspergillus (n = 4), Mucor (n = 1) pneumocystis (n = 1), Stenotrophomonas (n = 2), Klebsiella (n = 2), Pseudomonas (n = 1), Hemophilus influenzae (n = 1); Bacterial + Viral: CMV (n = 1), respiratory syncytial virus (n = 1), influenza (n = 1), Pseudomonas (n = 1), Enterobacter (n = 1), Legionella (n = 1); Fungal only: Aspergillus (n = 8), Mucorales (n = 3), pneumocystis, (n = 2); Viral only: CMV (n = 9), respiratory syncytial virus (n = 1), influenza (n = 1); Bacterial only: E. coli (n = 2), Staphylococcus aureus (n = 1), Klebsiella (n = 1), Pseudomonas (n = 1); Virus of uncertain lung pathogenicity: AdV (n = 4), HHV-6 (n = 3), HRV (n = 2), human bocavirus (n = 2), varicella zoster virus (n = 1), herpes simplex virus type 1 (n = 1). Only pathogen findings with established pathogenicity as outlined in Methods section were included in the first 7 groups.

Figure 3

Sensitivity of diagnostic tests in 16 patients with a documented diagnosis of probable invasive aspergillosis. Number of positive tests: BAL culture, 12 of 16 (sensitivity 75%; specificity 98%, PPV 92%, NPV 92%); BAL galactomannan, 13 of 15 (sensitivity 87%, specificity 92%, PPV 76%, NPV 96%); BAL PCR, 8 of 9 (sensitivity 89%, specificity 100%, PPV 100%, NPV 97%); and serum galactomannan, 6 of 14 (sensitivity 43%, specificity 92%, PPV 86%, NPV 86%). NPV indicates negative predictive value; PPV, positive predictive value.