Abstract
BackgroundLower respiratory tract infection (LRTI) is a major contributor to respiratory failure requiring intubation and mechanical ventilation. LRTI also occurs during mechanical ventilation, increasing the morbidity and mortality of intubated patients. We sought to understand the dynamics of respiratory tract microbiota following intubation and the relationship between microbial community structure and infection.ResultsWe enrolled a cohort of 15 subjects with respiratory failure requiring intubation and mechanical ventilation from the medical intensive care unit at an academic medical center. Oropharyngeal (OP) and deep endotracheal (ET) secretions were sampled within 24 h of intubation and every 48–72 h thereafter. Bacterial community profiling was carried out by purifying DNA, PCR amplification of 16S ribosomal RNA (rRNA) gene sequences, deep sequencing, and bioinformatic community analysis. We compared enrolled subjects to a cohort of healthy subjects who had lower respiratory tract sampling by bronchoscopy. In contrast to the diverse upper respiratory tract and lower respiratory tract microbiota found in healthy controls, critically ill subjects had lower initial diversity at both sites. Diversity further diminished over time on the ventilator. In several subjects, the bacterial community was dominated by a single taxon over multiple time points. The clinical diagnosis of LRTI ascertained by chart review correlated with low community diversity and dominance of a single taxon. Dominant taxa matched clinical bacterial cultures where cultures were obtained and positive. In several cases, dominant taxa included bacteria not detected by culture, including Ureaplasma parvum and Enterococcus faecalis.ConclusionsLongitudinal analysis of respiratory tract microbiota in critically ill patients provides insight into the pathogenesis and diagnosis of LRTI. 16S rRNA gene sequencing of endotracheal aspirate samples holds promise for expanded pathogen identification.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-016-0151-8) contains supplementary material, which is available to authorized users.
Highlights
Lower respiratory tract infection (LRTI) is a major contributor to respiratory failure requiring intubation and mechanical ventilation
Our goals were to (1) define the dynamics of the respiratory tract bacterial microbiome during mechanical ventilation, (2) identify features of bacterial community structure associated with LRTI, (3) assess the correlation between LRTI pathogens identified by clinical culture and 16S ribosomal RNA (rRNA) gene sequencing, and (4) detect dominant bacterial species that may not be not recognized by culture
Four subjects were given the clinical diagnosis of ventilator-associated pneumonia (VAP), and two subjects were suspected of having recurrent aspiration during the course of mechanical ventilation
Summary
Lower respiratory tract infection (LRTI) is a major contributor to respiratory failure requiring intubation and mechanical ventilation. We sought to understand the dynamics of respiratory tract microbiota following intubation and the relationship between microbial community structure and infection. 7.6 % of patients admitted to the hospital with community-acquired pneumonia (CAP) develop respiratory failure requiring mechanical ventilation [1, 2]. Similar proportions of patients who acquire pneumonia during hospitalization (HAP) require mechanical ventilation (5.9 %) [3]. The dynamics of the full microbial populations in the respiratory tract of intubated patient remain poorly understood. Routine clinical culture identifies only a subset of the respiratory tract community members. Culture-based analysis has limited sensitivity for fastidious organisms and anaerobes
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