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

• Published in: Biology of blood and marrow transplantation Vol. 24; no. 8; pp. 1707 - 1714
• Main Authors: Wohlfarth, Philipp, Turki, Amin T., Steinmann, Joerg, Fiedler, Melanie, Steckel, Nina K., Beelen, Dietrich W., Liebregts, Tobias
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2018; American Society for Blood and Marrow Transplantation
• Subjects: Acute Disease; Acute respiratory failure; Allografts; Aspergillus - isolation & purification; Blood - microbiology; Bronchoalveolar Lavage Fluid - microbiology; Disease Transmission, Infectious; Hematopoietic stem cell transplantation; Hematopoietic Stem Cell Transplantation - adverse effects; HSCT; Humans; ICU; Intensive care unit; Intensive Care Units; Middle Aged; Mucorales - isolation & purification; Respiratory Insufficiency - diagnosis; Respiratory Insufficiency - etiology; Respiratory Insufficiency - microbiology; Retrospective Studies; Transplant Recipients; Acute respiratory failure; ICU; HSCT; Intensive care unit; Hematopoietic stem cell transplantation
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2018.03.007

•A broad molecular- and biomarker-based microbiologic workup identified causative pathogens in 70% of HSCT recipients with acute respiratory failure admitted to the intensive care unit.•Fungi were the most frequently detected pathogens (42%), followed by viruses (40%) and bacteria (27%). Polymicrobial findings involving several pathogen groups occurred in 30% of patients.•Bronchoalveolar lavage may enhance pathogen detection and therapy guidance in settings of high prevalence of invasive mold infections including non-Aspergillus strains and emerging azole resistance. 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.