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Metabolomic profiling of microbial disease etiology in community-acquired pneumonia.

ABSTRACT: Diagnosis of microbial disease etiology in community-acquired pneumonia (CAP) remains challenging. We undertook a large-scale metabolomics study of serum samples in hospitalized CAP patients to determine if host-response associated metabolites can enable diagnosis of microbial etiology, with a specific focus on discrimination between the major CAP pathogen groups S. pneumoniae, atypical bacteria, and respiratory viruses. Targeted metabolomic profiling of serum samples was performed for three groups of hospitalized CAP patients with confirmed microbial etiologies: S. pneumoniae (n = 48), atypical bacteria (n = 47), or viral infections (n = 30). A wide range of 347 metabolites was targeted, including amines, acylcarnitines, organic acids, and lipids. Single discriminating metabolites were selected using Student's T-test and their predictive performance was analyzed using logistic regression. Elastic net regression models were employed to discover metabolite signatures with predictive value for discrimination between pathogen groups. Metabolites to discriminate S. pneumoniae or viral pathogens from the other groups showed poor predictive capability, whereas discrimination of atypical pathogens from the other groups was found to be possible. Classification of atypical pathogens using elastic net regression models was associated with a predictive performance of 61% sensitivity, 86% specificity, and an AUC of 0.81. Targeted profiling of the host metabolic response revealed metabolites that can support diagnosis of microbial etiology in CAP patients with atypical bacterial pathogens compared to patients with S. pneumoniae or viral infections.

SUBMITTER: den Hartog I

PROVIDER: S-EPMC8177549 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe etiology of community-acquired pneumonia (CAP) has evolved since the beginning of the antibiotic era. Recent guidelines encourage immediate empiric antibiotic treatment once a diagnosis of CAP is made. Concerns about treatment recommendations, on the one hand, and antibiotic stewardship, on the other, motivated this review of the medical literature on the etiology of CAP.MethodsWe conducted a systematic review of English-language literature on the etiology of CAP using methods defined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed using a combination of the keywords 'pneumonia', 'CAP', 'etiology', 'microbiology', 'bacteriology', and 'pathogen'. We examined articles on antibiotics that were develop to treat pneumonia. We reviewed all 'related articles' as well as studies referenced by those that came up in the search. After we excluded articles that did not give sufficient microbiological data or failed to meet other predetermined criteria, 146 studies remained. Data were stratified into diagnostic categories according to the microbiologic studies that were done; results are presented as the percentage in each category of all cases in which an etiology was established.ResultsStreptococcus pneumoniae remains the most common cause of CAP although declining in incidence; this decline has been greater in the US than elsewhere. Haemophilus influenzae is the second most common cause of CAP, followed by Staphylococcus aureus and Gram negative bacilli. The incidence of all bacteria as causes of CAP has declined because, with routine use of PCR for viruses, the denominator, cases with an established etiology, has increased. Viruses were reported on average in about 10% of cases, but recent PCR-based studies identified a respiratory virus in about 30% of cases of CAP, with substantial rates of viral/bacterial coinfection.ConclusionThe results of this study justify current guidelines for initial empiric treatment of CAP. With pneumococcus and Haemophilus continuing to predominate, efforts at antibiotic stewardship might be enhanced by greater attention to the routine use of sputum Gram stain and culture. Because viral/bacterial coinfection is relatively common, the identification of a virus by PCR does not, by itself, allow for discontinuation of the antibiotic therapy.

Project description:BackgroundChildhood community acquired pneumonia (CAP) is a significant problem in developing countries, and confirmation of microbial etiology is important for individual, as well as public health. However, there is paucity of data from a large cohort, examining multiple biological specimens for diverse pathogens (bacteria and viruses). The Community Acquired Pneumonia Etiology Study (CAPES) was designed to address this knowledge gap.MethodsWe enrolled children with CAP (based on WHO IMCI criteria of tachypnea with cough or breathing difficulty) over 24 consecutive months, and recorded presenting symptoms, risk factors, clinical signs, and chest radiography. We performed blood and nasopharyngeal aspirate (NPA) bacterial cultures, and serology (Mycoplasma pneumoniae, Chlamydophila pneumoniae). We also performed multiplex PCR for 25 bacterial/viral species in a subgroup representing 20% of the cohort. Children requiring endotracheal intubation underwent culture and PCR of bronchoalveolar lavage (BAL) specimens.FindingsWe enrolled 2345 children. NPA and blood cultures yielded bacteria in only 322 (13.7%) and 49 (2.1%) children respectively. In NPA, Streptococcus pneumoniae (79.1%) predominated, followed by Haemophilus influenzae (9.6%) and Staphylococcus aureus (6.8%). In blood, S. aureus (30.6%) dominated, followed by S. pneumoniae (20.4%) and Klebsiella pneumoniae (12.2%). M. pneumoniae and C. pneumoniae serology were positive in 4.3% and 1.1% respectively. Multiplex PCR in 428 NPA specimens identified organisms in 422 (98.6%); of these 352 (82.2%) had multiple organisms and only 70 (16.4%) had a single organism viz. S. pneumoniae: 35 (50%), Cytomegalovirus (CMV): 13 (18.6%), Respiratory Syncytial Virus (RSV): 9 (12.9%), other viruses: 6 (8.7%), S. aureus: 5 (7.1%), and H. influenzae: 2 (2.9%). BAL PCR (n?=?30) identified single pathogens in 10 (S. pneumoniae-3, CMV-3, S. aureus-2, H. influenzae-2) and multiple pathogens in 18 children. There were 108 (4.6%) deaths. The pattern of pathogens identified did not correlate with pneumonia severity or mortality.ConclusionsThe majority of children with CAP have multiple pathogens (bacteria and viruses). S. pneumoniae and S. aureus predominate in NPA and blood respectively. CMV and RSV were the dominant respiratory viruses in NPA and BAL. The presence of multiple pathogens, especially organisms associated with nasopharyngeal carriage, precludes confirmation of a causal relationship in most cases.

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Metabolomic profiling of microbial disease etiology in community-acquired pneumonia.

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