Community-acquired pneumonia (CAP) is the leading cause of death in children < 5 years of age worldwide. It is also one of the most frequent infectious diseases in children, leading to large antibiotic use and hospitalization even in the industrialized countries. However, the optimal management of CAP in children is still not well defined. Currently, respiratory viruses are considered the most frequent etiologic agents, but detection of viruses in the upper respiratory tract does not guarantee causation of pneumonia, nor precludes the presence of a bacterial pathogen. In both the upper and lower respiratory tract, respiratory viruses and pathogenic bacteria interact. Emerging evidence indicates that dual viral–bacterial infections function synergistically in many cases and together likely enhance the severity of CAP. Therefore, new and advanced technologies capable of sensitively and specifically discriminating viral, bacterial, and viral–bacterial coinfections are needed. Instead of focusing on the pathogen, analysis of host immune transcriptome profiles from children with CAP can potentially offer diagnostic signatures, help to assess disease severity, and eventually, prognostic indicators. An optimized management strategy by using molecular pathogen testing and transcriptome profiling will facilitate prompt, more appropriate, and targeted therapies, which in turn will lead to improved clinical outcomes in children with CAP.

Background The role of nasopharyngeal bacteria on RSV disease has been underestimated. We measured the frequency and quantitative detection of potentially pathogenic bacteria in the upper respiratory tract of infants with RSV infection over seven respiratory seasons, and their impact on clinical outcomes. Methods Children &lt;2 years old with mild (outpatients; n=115) or severe (inpatients; n=566) RSV infection, and matched healthy controls (n=161) were prospectively enrolled. Nasopharyngeal samples were obtained for RSV, S. pneumoniae, S. aureus, M. catarrhalis, and H. influenzae detection and quantitation by PCR. Multivariable models were constructed to identify variables predictive of severe disease. Results S. pneumoniae, H. influenzae, and M. catarrhalis, but not S. aureus, were detected more frequently in RSV-infected children (84%) than healthy controls (46%; p&lt;0.001). Detection of S. pneumoniae and/or H. influenzae was associated with fever, more frequent antibiotic treatment, worse radiologic findings, and higher neutrophil counts (p&lt;0.01). In adjusted analyses S. pneumoniae/H. influenzae co-detection was associated with greater odds (OR; 95% CI) of hospitalization (2.25 [1.07-4.74), higher disease severity scores (1.93 [1.14-3.26]), prolonged oxygen administration (2.23 [1.01-4.91]), and longer hospitalization (2.53 [1.33-4.79]). Conclusions Nasopharyngeal co-detection of S. pneumoniae and H. influenzae in infants with RSV infection is associated with increased disease severity.

BackgroundPrevious studies suggest that RSV increases NP bacterial colonization and may facilitate infection. However, the role of NP colonization with potentially pathogenic bacteria (PPB) in the pathogenesis of RSV bronchiolitis is not well understood. We sought to determine the frequency, type, and density of NP PPB detection in infants with RSV infection compared with healthy controls (HC), and its association with clinical outcomes.MethodsSingle-center, prospective study of previously healthy infants with RSV infection and age-matched HC. Inpatients (IP) were enrolled within 24 hours of hospitalization, outpatients (OP) at the ED or primary clinics and HC at well-child visits. RSV infection and the following PPB: [S. pneumoniae, M. catarrhalis, H. influenzae, and S. aureus] were detected and quantified by PCR. We compared demographic, clinical characteristics, and outcomes of care according to NP PPB detection.ResultsFrom 2010 to 2018, we enrolled 815 infants: 664 with RSV infection [IP, 560; OP, 104] and 151 HC. RSV+ OP (6.1 [3.7–10.7] months) and HC (6.9 [3.8–10.8] months) were older than IP (2.5 [1.4–5.4] months; P < 0.001). Identification of ≥1 PPB was 89% in RSV+ infants [IP, 88%; OP, 90%] versus 63% of HC (P < 0.0001). While H. influenzae or >1 PPB detection was higher in RSV infection (P < 0.001), S. aureus detection predominated in HC (P < 0.05; Figure 1). Frequency of S. pneumoniae detection was comparable between groups; however, S. pneumoniae loads were one log higher in RSV+ infants versus HC (P = 0.001) adjusted for antibiotic use. Differences in colonization rates remained different in RSV+ infants versus HC across age ranges (<3, 3–6, >6–12, and >12–24 months; Figure 2). Last, RSV patients (both IP and OP) with S. pneumoniae or H. influenzae detection had fever more frequently (70%–74% vs. 25%–47%; P < 0.0001), higher clinical disease severity scores (P = 0.01), and higher blood neutrophil counts (34%–36% vs. 16%–19%; P < 0.001), versus those with M. catarrhalis, S. aureus detection or PCR negative. In addition, NP detection of H. influenzae in RSV children was associated with higher frequency of atelectasis/consolidation by chest X-ray (P < 0.005).ConclusionThese data suggest that NP colonization with PPB is high in infants with RSV infection independent of age, and that specific bacteria, namely S. pneumoniae and H. influenzae, are associated with enhanced clinical disease severity. Disclosures A. Leber, Nationwide Children’s Hospital: Research Contractor, Research support. O. Ramilo, Janssen Scientific Affairs, LLC: Consultant, Consulting fee. A. Mejias, Janssen: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Abbvie: CME talks, Speaker honorarium.

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Background Streptococcus pneumoniae is the most common pyogenic bacteria associated with CAP in children, but the proportion of cases might be underestimated because of the low sensitivity of current standard diagnostic methods. Nasopharyngeal (NP) carriage of pneumococcus commonly precedes the development of pneumococcal pneumonia, and facilitates pneumococcus interactions with other respiratory pathogens and the host immune response. This study investigated the relationship between pneumococcal carriage and the severity of CAP in children.MethodsWe conducted a prospective, multicenter, observational study for CAP among previously healthy children aged 2 months through 18 years in six children’s hospitals in Ohio. Blood, pleural fluid, and NP swabs were collected for pathogen detection by culture and/or polymerase chain reaction (PCR). S. pneumoniae was quantified in NP swabs by real-time PCR. Patient management followed the standard of care in each study site.ResultsAmong 441 children with radiologically confirmed CAP, 156 (35.4%) had no bacterial or viral pathogens identified as etiologic agents. NP pneumococcal carriage rate in this group was 34.6%. Children with CAP and pneumococcal carriage (53/156) were younger (5.9 vs. 9.6 years, P < 0.001) than those with no carriage (103/156). Median neutrophil counts and median procalcitonin concentrations were significantly higher in the pneumococcal carriage group (12,030 vs. 8,370 cells/mm3 and 1.0 vs. 0.5 mg/dl, respectively; P < 0.05 for both) than in the non-carriage group. Children with documented pneumococcal carriage received respiratory support more frequently (50.0% vs. 28.2%, p = 0.012) and had a longer duration of hospitalization (3.5 ± 3.8 vs. 2.1 ± 2.0 days, P = 0.026) than those without pneumococcal carriage. Age was not associated with any of the variables used to assess clinical disease severity.ConclusionPneumococcal carriage was associated with higher inflammatory markers and greater clinical disease severity in children with CAP in whom no pathogens were identified by standard diagnostics. This suggests that NP carriage of pneumococcus in children with CAP may modulate the host immune response and possibly influence clinical disease severity.DisclosuresOctavio Ramilo, MD, Bill & Melinda Gates Foundation: Research Grant; Janssen: Research Grant; Merck: Advisory Board; NIH: Research Grant; Ohio Children’s Hospital Association (OCHA): Research Grant; Pfizer: Advisory Board, Consultant, Lectures; Sanofi/Medimmune: Advisory Board.