Background Intensive studies have failed to identify an etiologic agent in >50% cases of community-acquired pneumonia (CAP). Bacterial pneumonia follows aspiration of recognized bacterial pathogens (RBPs) such as Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus after they have colonize the nasopharynx. We hypothesized that aspiration of normal respiratory flora (NRF) might also cause CAP. Methods We studied 120 patients hospitalized for CAP who provided a high-quality sputum specimen at, or soon after admission, using Gram stain, quantitative sputum culture, bacterial speciation by matrix-assisted laser desorption ionization time-of-flight, and viral polymerase chain reaction. Thresholds for diagnosis of bacterial infection were ≥105 colony-forming units (cfu)/mL sputum for RBPs and ≥106 cfu for NRF. Results Recognized bacterial pathogens were found in 68 of 120 (56.7%) patients; 14 (20.1%) of these had a coinfecting respiratory virus. Normal respiratory flora were found in 31 (25.8%) patients; 10 (32.2%) had a coinfecting respiratory virus. Infection by ≥2 RBPs occurred in 10 cases and by NRF together with RBPs in 13 cases. Among NRF, organisms identified as Streptococcus mitis, which share many genetic features of S pneumoniae, predominated. A respiratory virus alone was found in 16 of 120 (13.3%) patients. Overall, an etiologic diagnosis was established in 95.8% of cases. Conclusions Normal respiratory flora, with or without viral coinfection, appear to have caused one quarter of cases of CAP and may have played a contributory role in an additional 10.8% of cases caused by RBPs. An etiology for CAP was identified in >95% of patients who provided a high-quality sputum at, or soon after, the time of admission.

No abstract

No abstract

Background The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure. Methods We profiled 127 hospitalized patients with COVID-19 (n = 79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites. Results Forty-eight species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or “long COVID,” suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with classifying whether stool was obtained from patients with severe vs. moderate COVID-19, a finding that was externally validated in an independent cohort. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease. Conclusions Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to expand upon these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention.

BackgroundIntensive studies have failed to identify an etiologic agent in >50% of patients (patients) who are hospitalized for community-acquired pneumonia (CAP). Gram stain and culture of sputum samples frequently yield “normal respiratory flora” (NRF). We hypothesized that careful study might (1) increase the yield of recognized pathogens; and (2) show, in some patients, an etiologic role for NRF.MethodsWe studied a convenience sample of adults hospitalized for CAP at a VA Medical Center if they met four criteria: (1) clinical syndrome consistent with pneumonia; (2) newly recognized pulmonary infiltrate; (3) sputum with > 10 WBC per epithelial cell; and (4) < 18 hours antibiotic treatment. For quantification of bacteria, sputum was liquefied in 2% N-acetyl cysteine and diluted serially. Other studies in nearly all patients included blood cultures, urine for pneumococcal (Spn) and Legionella antigen, procalcitonin, B-natriuretic protein and PCR for 13 respiratory viruses, Mycoplasma and Chlamydia. >106 bacteria/mL and a consistent Gram stain indicated a bacterial cause, positive viral PCR indicated a viral cause, and both indicated coinfection.Results119 patients met study criteria. Recognized bacterial pathogens alone were identified in 47 (40%) cases led by Spn 17 (14%), Haemophilus 17 (14%) and S. aureus 6 (5%). A virus alone was identified in 17 (15%) and coinfection in 11 (9%). We applied these same criteria for NRF. NRF alone were found in 22 (19%) patients with S. mitis predominating. NRF and a respiratory virus were coinfecting in 10 (8%) patients. In total, with the inclusion of NRF, an etiologic agent was found in 95% of patients.ConclusionOur high yield is attributable to selection criteria. With a good-quality sputum and absent prolonged antibiotics, a bacterial cause for CAP was found in 59% of patients, a viral cause in 15%, and coinfection in 17%. Bacterial CAP due to recognized pathogen follows microaspiration of colonizing bacteria from the upper airways. Aspiration of a sufficient inoculum of so-called NRF, especially in older adults or those with damaged clearance mechanisms, might well do the same. Careful microbiologic study of patients who are able to provide a valid sputum sample before prolonged antibiotics enables a microbiologic diagnosis in nearly all cases and shows a potential etiologic role for NRF in about 20%. Disclosures All authors: No reported disclosures.

No abstract

No abstract

The airway microbiome in persons with cystic fibrosis (pwCF) is correlated with lung function and disease severity. Supplemental oxygen use is common in more advanced CF, yet its role in perturbing airway microbial communities is unknown.