Bacterial pneumonia is a major cause of morbidity and mortality in elderly. We hypothesize that dysbiosis between regular residents of the upper respiratory tract (URT) microbiome, that is balance between commensals and potential pathogens, is involved in pathogen overgrowth and consequently disease. We compared oropharyngeal microbiota of elderly pneumonia patients (n = 100) with healthy elderly (n = 91) by 16S-rRNA-based sequencing and verified our findings in young adult pneumonia patients (n = 27) and young healthy adults (n = 187). Microbiota profiles differed significantly between elderly pneumonia patients and healthy elderly (PERMANOVA, Po0.0005). Highly similar differences were observed between microbiota profiles of young adult pneumonia patients and their healthy controls. Clustering resulted in 11 (sub)clusters including 95% (386/405) of samples. We observed three microbiota profiles strongly associated with pneumonia (Po0.05) and either dominated by lactobacilli (n = 11), Rothia (n = 51) or Streptococcus (pseudo)pneumoniae (n = 42). In contrast, three other microbiota clusters (in total n = 183) were correlated with health (Po0.05) and were all characterized by more diverse profiles containing higher abundances of especially Prevotella melaninogenica, Veillonella and Leptotrichia. For the remaining clusters (n = 99), the association with health or disease was less clear. A decision tree model based on the relative abundance of five bacterial community members in URT microbiota showed high specificity of 95% and sensitivity of 84% (89% and 73%, respectively, after cross-validation) for differentiating pneumonia patients from healthy individuals. These results suggest that pneumonia in elderly and young adults is associated with dysbiosis of the URT microbiome with bacterial overgrowth of single species and absence of distinct anaerobic bacteria. Whether the observed microbiome changes are a cause or a consequence of the development of pneumonia or merely coincide with disease status remains a question for future research.
Current diagnostics for community-acquired pneumonia (CAP) include testing for a wide range of pathogens, which is costly and not always informative. We compared clinical and laboratory parameters of patients with CAP caused by different groups of pathogens to evaluate the potential for targeted diagnostics and directed treatment. In a prospective study, conducted between April 2008 and April 2009, adult patients with CAP were tested for the presence of a broad range of possible respiratory pathogens using bacterial cultures, PCR, urinary antigen testing and serology. Of 408 patients with CAP, pathogens were detected in 263 patients (64.5 %). Streptococcus pneumoniae and influenza A virus were the most frequently identified bacterial and viral pathogens, respectively. Age had a significant effect on the prediction of aetiology (P50.054), with an increase in the relative contribution of viruses with advancing age. Multivariate analyses further showed that the presence of cough increased the likelihood of detecting a viral pathogen [odds ratio (OR) 5.536, 95 % confidence interval (CI) 2.130-14.390], the presence of immunodeficiency decreased the likelihood of detecting a bacterial pathogen (OR 0.595,) and an increase in pneumonia severity index score increased the likelihood of detecting a pathogen in general. Although several variables were independently associated with the detection of a pathogen group, substantial overlap meant there were no reliable clinical predictors to distinguish aetiologies. Therefore, testing for common respiratory pathogens is still necessary to optimize treatment.
BackgroundAcute respiratory tract infections are an important public health problem. Sensitive and rapid diagnostic techniques have been developed and are used in daily clinical practice. Here we evaluate the clinical relevance of detecting 20 common respiratory pathogens by molecular methods in a general pediatric clinic.MethodsNasopharynx samples of children < 18 years of age with respiratory symptoms referred to a general pediatric clinic were tested for the presence of 19 viruses and Mycoplasma pneumoniae, using real-time polymerase chain reaction.ResultsOf 177 patients included in this retrospective study, 73% were positive for at least one virus. Respiratory syncytial virus (36.6%) and human rhinovirus (24%) were most frequently detected. Patients in whom a respiratory virus or Mycoplasma pneumoniae was detected, were younger (6 versus 24 months; p < 0.001) and more often hospitalized (116 versus 34; p = 0.001) than patients in whom no respiratory pathogen was detected. Also they were more likely to present with feeding problems, dyspnea, rhinorrhea and wheezing (all p < 0.05) than patients without a respiratory pathogen.In the majority of cases, clinicians did not change their antibiotic management after detecting a viral respiratory pathogen. No difference in mean Ct value was found between patients with one respiratory pathogen and those with >1 respiratory pathogen (30.5 versus 31.2; p = 0.573).ConclusionRoutine testing of common respiratory pathogens could lead to a better understanding of their role in disease in children with respiratory symptoms.
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