Abstract
BackgroundThe aim of the study was to evaluate the composition and the temporal evolution of the oropharyngeal microbiome in antibiotic-naïve patients requiring mechanical ventilation and to gain new insights into the pathogenesis of ventilator-associated pneumonia (VAP).MethodsProspective, observational single-center nested case-control study. Patients with acute critical illness and anticipated duration of mechanical ventilation > 4 days were eligible. We took oropharyngeal swabs (and if available, tracheal secretions) daily, starting at the day of intubation. The microbiota was characterized by 16S rRNA high-throughput sequencing and compared between patients developing VAP versus controls.ResultsFive patients developed VAP. In three patient the causative pathogens were Enterobacteriaceae and in two Haemophilus influenzae. Locally weighted polynomial regression suggested that the within diversity (=alpha) was lower in Enterobacteriaceae VAP patients between days two to five of mechanical ventilation when compared to controls. Detection of Enterobacteriaceae in the oropharynx occurred on day two of follow-up and consisted of a single operational taxonomic unit in 2/3 patients with enterobacterial VAP.ConclusionsIn acutely-ill patients who developed enterobacterial VAP the causative pathogen gained access to the oropharynx early after starting mechanical ventilation and outgrew the commensal members of the microbiome. Whether a specific pattern of the oropharyngeal microbiome between days three to five of mechanical ventilation may predict VAP enterobacterial VAP has to be evaluated in further studies.
Highlights
The aim of the study was to evaluate the composition and the temporal evolution of the oropharyngeal microbiome in antibiotic-naïve patients requiring mechanical ventilation and to gain new insights into the pathogenesis of ventilator-associated pneumonia (VAP)
We addressed the potential bias of misclassifying cases into VAP and controls by having the diagnostic criteria validated by an independent study nurse
Five had a confirmed VAP between days 5–7 after inclusion (Fig. 2). Of these five VAP patients, a microbiological diagnosis was obtained by conventional culture methods in four subjects – and by microbiome analysis in one subject (Proteus vulgaris being the causative operational taxonomic unit)
Summary
The aim of the study was to evaluate the composition and the temporal evolution of the oropharyngeal microbiome in antibiotic-naïve patients requiring mechanical ventilation and to gain new insights into the pathogenesis of ventilator-associated pneumonia (VAP). Ventilator-associated pneumonia (VAP) is the most common hospital-acquired infection in intensive care units (ICU), and is associated with prolonged mechanical ventilation, increased mortality, higher costs, and increased antibiotic consumption [1,2,3,4]. Most measures to decrease VAP rates aim at preventing the transfer of pathogens from the oropharynx to the lungs [6]. The human lung microbiome and its role in health and disease has gained greater attention among researchers in the last. During influenza infection, the respiratory microbiome seems to undergo only very discrete changes [18]
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