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Respiratory Tract Dysbiosis Is Associated with Worse Outcomes in Mechanically Ventilated Patients.

ABSTRACT: Rationale: Host inflammatory responses have been strongly associated with adverse outcomes in critically ill patients, but the biologic underpinnings of such heterogeneous responses have not been defined.Objectives: We examined whether respiratory tract microbiome profiles are associated with host inflammation and clinical outcomes of acute respiratory failure.Methods: We collected oral swabs, endotracheal aspirates (ETAs), and plasma samples from mechanically ventilated patients. We performed 16S ribosomal RNA gene sequencing to characterize upper and lower respiratory tract microbiota and classified patients into host-response subphenotypes on the basis of clinical variables and plasma biomarkers of innate immunity and inflammation. We derived diversity metrics and composition clusters with Dirichlet multinomial models and examined our data for associations with subphenotypes and clinical outcomes.Measurements and Main Results: Oral and ETA microbial communities from 301 mechanically ventilated subjects had substantial heterogeneity in α and β diversity. Dirichlet multinomial models revealed a cluster with low α diversity and enrichment for pathogens (e.g., high Staphylococcus or Pseudomonadaceae relative abundance) in 35% of ETA samples, associated with a hyperinflammatory subphenotype, worse 30-day survival, and longer time to liberation from mechanical ventilation (adjusted P < 0.05), compared with patients with higher α diversity and relative abundance of typical oral microbiota. Patients with evidence of dysbiosis (low α diversity and low relative abundance of "protective" oral-origin commensal bacteria) in both oral and ETA samples (17%, combined dysbiosis) had significantly worse 30-day survival and longer time to liberation from mechanical ventilation than patients without dysbiosis (55%; adjusted P < 0.05).Conclusions: Respiratory tract dysbiosis may represent an important, modifiable contributor to patient-level heterogeneity in systemic inflammatory responses and clinical outcomes.

SUBMITTER: Kitsios GD

PROVIDER: S-EPMC7737572 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Potential interactions between the SARS-CoV-2 virus and the human oral microbiota are currently investigated widely. Patients with COVID-19 requiring mechanical ventilation in an intensive care unit (ICU) setting are at high risk of developing severe complications, including ventilator-associated pneumonia, thus making oral health management important. The aim of this study was to evaluate the oral health status and assess the dysbiosis of cultivable oral bacteriota in COVID-19 patients hospitalized in an ICU with acute respiratory distress within 36 h following intubation. In this prospective cohort study, we recruited 56 adult COVID-19 patients that qualified for mechanical ventilation in the Temporary ICU for COVID-19 Patients of the University Hospital in Krakow. On admission to the ICU, oral health of patients was assessed using the modified Beck Oral Assessment Score (BOAS). Four oral habitats were sampled, namely the buccal mucosa, tongue, buccal dental surface and gingival pocket. Microorganisms were identified by MALDI/TOF mass spectrometry. The mean age of the study population was 66.5 ± 12.7 years, there were 24 (42.9%) females. All patients included in this study were intubated and ventilated in the ICU, with a corresponding high mortality rate (76.8%). On admission to ICU, 76.8% subjects scored 11-20 on the BOAS scale (median 12 [IQR 10-14]), indicating moderate or severe dysfunction of oral health. Potentially pathogenic bacteria were identified in the oral microbiota samples, including Acinetobacter baumannii, Enterococcus faecalis, Escherichia coli and Klebsiella pneumoniae in 23.2%, 39.3%, 17.9%, and 19.6% of patients, respectively. Lactobacillus spp. were present in 57.1% subjects. The mean CFU counts of all bacteria strains in dental brushes were 9.3E+5 (1.4E+6) and in gingival pockets 7.6E+5 (1.4E+6). The highest CFU counts were observed for Enterococcus spp. and, Lactobacillus spp., although these did not differ significantly from CFU counts of Streptococcus spp. and Staphylococcus spp. In this report we comprehensively characterized the oral health condition and cultivable oral bacteriota in COVID-19 patients hospitalized in an ICU with acute respiratory distress within 36 h following intubation. The oral bacteriota showed significant qualitative and quantitative dysbiosis. Hospitalization in an ICU and mechanical ventilation are important factors leading to oral dysbiosis in SARS-CoV-2 patients.

Project description:Staphylococcus aureus is a commensal and frequent colonizer of the upper respiratory tract. When mechanical ventilation disrupts natural defenses, S. aureus is frequently isolated from the lower airways, but distinguishing between colonization and infection is difficult. The objectives of this study were (1) to investigate the bacterial genome sequence in consecutive isolates in order to identify changes related to the pathological adaptation to the lower respiratory tract and (2) to explore the relationship between specific phenotypic and genotypic features with the patient's study group, persistence of the clinical isolate and clinical outcome. A set of 94 clinical isolates were selected and corresponded to 34 patients that were classified as having pneumonia (10), tracheobronchitis (11) and bronchial colonization (13). Clinical strains were phenotypically characterized by conventional identification and susceptibility testing methods. Isolates underwent whole genome sequencing using Illumina HiSeq4000. Genotypic characterization was performed with an in-house pipeline (BacterialTyper). Genomic variation arising within-host was determined by comparing mapped sequences and de novo assemblies. Virulence factors important in staphylococcal colonization and infection were characterized using previously established functional assays. (1) Toxin production was assessed using a THP-1 cytotoxicity assay, which reports on the gross cytotoxicity of individual isolates. In addition, we investigated the expression of the major virulence factor, alpha-toxin (Hla) by Western blot. (2) Adhesion to the important extracellular matrix molecule, fibronectin, was determined using a standardized microtitre plate assay. Finally, invasion experiments using THP-1 and A539 cell lines and selected clinical strains were also performed. Repeated isolation of S. aureus from endotracheal aspirate usually reflects persistence of the same strain. Within-host variation is detectable in this setting, but it shows no evidence of pathological adaptation related to virulence, resistance or niche adaptations. Cytotoxicity was variable among isolates with 14 strains showing no cytotoxicity, with these latter presenting an unaltered Fn binding capacity. No changes on cytotoxicity were reported when comparing study groups. Fn binding capacity was reported for almost all strains, with the exception of two strains that presented the lowest values. Strains isolated from patients with pneumonia presented a lower capacity of adhesion in comparison to those isolated during tracheobronchitis (p = 0.002). Hla was detected in 71 strains (75.5%), with most of the producer strains in pneumonia and bronchial colonization group (p = 0.06). In our cohort, Hla expression (presence or absence) in sequential isolates was usually preserved (70%) although in seven cases the expression varied over time. No relationship was found between low cytotoxicity and intracellular persistence in invasion experiments. In our study population, persistent S. aureus isolation from airways in ventilated patients does not reflect pathological adaptation. There is an important diversity of sequence types. Cytotoxicity is variable among strains, but no association with study groups was found, whereas isolates from patients with pneumonia had lower adhesion capability. Favorable clinical outcome correlated with increased bacterial adhesion in vitro. Most of the strains isolated from the lower airways were Hla producers and no correlation with an adverse outcome was reported. The identification of microbial factors that contribute to virulence is relevant to optimize patient management during lower respiratory tract infections.

Project description:RATIONALE:Physicians are increasingly being held accountable for patient outcomes, yet their specific contribution to the outcomes remains uncertain. OBJECTIVES:To determine variation in outcomes of mechanically ventilated patients among intensivists, as well as associations between intensivist experience and patient outcomes. METHODS:We performed a retrospective cohort study of mechanically ventilated Medicare fee-for-service patients in acute care hospitals in Pennsylvania using administrative, clinical, and physician data from Centers for Medicare and Medicaid Services and the American Medical Association from 2008 and 2009. We identified intensivists by training background, board certification, and claims for services provided to patients admitted to an intensive care unit. We assigned patients to intensivists for outcome attribution based on submitted claims for critical care and in-patient services. We estimated the physician-specific adjusted odds ratios (ORs) for 30-day mortality using a hierarchical model with a random effect for physician, adjusted for patient and hospital characteristics. We tested for independent association of physician experience with patient outcomes using mixed-effects regression for the primary outcome of 30-day mortality. We defined physician experience in two ways: years since training completion ("duration") and annual number of mechanically ventilated patients ("volume"). RESULTS:We assigned 345 physicians to 11,268 patients. The 30-day mortality was 43% and median hospital length of stay was 11 days (interquartile range = 6-18). The physician adjusted OR varied from 0.72 to 1.64 (median = 0.99; interquartile range = 0.92-1.09). A total of 48% of physicians was outliers, with an adjusted OR significantly different from 1. However, among intensivists, physician experience was not associated with 30-day mortality (duration OR = 1.00 per additional year; 95% confidence interval = 1.00-1.01; volume OR = 1.00 per additional patient; 95% confidence interval = 1.00-1.00). CONCLUSIONS:Intensivists independently contribute to outcomes of Medicare patients who undergo mechanical ventilation, as evidenced by the variation in risk-adjusted mortality across intensivists. However, physician experience does not underlie this relationship between intensivists, suggesting the need to identify modifiable physician factors to improve outcomes.

Project description:BackgroundHerpes simplex virus (HSV) is frequently detected in the respiratory tract of mechanically ventilated patients. The aim of this study was to assess current evidence to determine whether antiviral therapy is associated with better outcomes in these patients.MethodsMEDLINE, ISI Web of Science, Cochrane Database and ClinicalTrials.gov were searched from inception to 25 May 2020. All clinical studies investigating the effects of antiviral therapy on the outcome of mechanically ventilated ICU patients in whom HSV was detected in the respiratory tract were eligible for inclusion, regardless of study design, publication status or language. Titles and abstracts were reviewed independently by two authors. If the articles seemed eligible, full-text articles were reviewed and data extracted. We performed a random-effects meta-analysis to estimate relative risks (RRs) with corresponding 95% confidence intervals (CIs). The primary endpoint was hospital all-cause mortality.ResultsNine studies were included in the meta-analysis (one randomized controlled trial, eight cohort studies). Antiviral treatment was associated with lower hospital mortality (with antiviral treatment, 40.6% (189 out of 465 patients); without, 52.7% (193 out of 366 patients); RR 0.74 [0.64, 0.85]; eight studies, low quality of evidence). Furthermore, antiviral treatment was associated with lower 30-day mortality (RR 0.75 [0.59, 0.94]; three studies, very low quality of evidence). We did not observe evidence for differences in ICU mortality (RR 0.73 [0.51, 1.05]; three studies, very low quality of evidence).ConclusionsThis meta-analysis of the available data shows that antiviral therapy might result in lower hospital and 30-day all-cause mortality in mechanically ventilated ICU patients who are positive for HSV in the respiratory tract. However, this result must be interpreted with great caution due to the high risk of bias and limited number of patients. Large, well-designed randomized controlled clinical trials are urgently needed.Trial registrationThe study was registered in advance on International Prospective Register of Systematic Reviews (CRD42020180053) .

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Respiratory Tract Dysbiosis Is Associated with Worse Outcomes in Mechanically Ventilated Patients.

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