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Background: Data on how respiratory syncytial virus (RSV) genotypes influence disease severity and host immune responses is limited. Here, we characterized the genetic variability of RSV during 5 seasons, and evaluated the role of RSV subtypes, genotypes, and viral loads in disease severity and host transcriptional profiles.Methods: A prospective, observational study was carried out, including a convenience sample of healthy infants hospitalized with RSV bronchiolitis. Nasopharyngeal samples for viral load quantitation, typing, and genotyping, and blood samples for transcriptome analyses were obtained within 24 hours of hospitalization. Multivariate models were constructed to identify virologic and clinical variables predictive of clinical outcomes.Results: We enrolled 253 infants (median age 2.1 [25%-75% interquartile range] months). RSV A infections predominated over RSV B and showed greater genotype variability. RSV A/GA2, A/GA5, and RSV B/BA were the most common genotypes identified. Compared to GA2 or BA, infants with GA5 infections had higher viral loads. GA5 infections were associated with longer hospital stay, and with less activation of interferon and increased overexpression of neutrophil genes.Conclusions: RSV A infections were more frequent than RSV B, and displayed greater variability. GA5 infections were associated with enhanced disease severity and distinct host immune responses. [ABSTRACT FROM AUTHOR]

Background. Respiratory syncytial virus (RSV) and influenza virus are common causes of infantile lower respiratory tract infection (LRTI). It is widely believed that both viral replication and inappropriately enhanced immune responses contribute to disease severity. In infants, RSV LRTI is known to be more severe than influenza virus LRTI. Methods. We compared cytokines and chemokines in secretions of infants surviving various forms of respiratory illness caused by RSV or influenza viruses, to determine which mediators were associated with more-severe illness. We analyzed lung tissue from infants with fatal cases of RSV and influenza virus LRTI to determine the types of inflammatory cells present. Autopsy tissues were studied for the lymphotoxin granzyme and the apoptosis marker caspase 3. Results. Quantities of lymphocyte-derived cytokines were minimal in secretions from infants with RSV infection. Concentrations of most cytokines were greater in influenza virus, rather than RSV, infection. Lung tissues from infants with fatal RSV and influenza virus LRTI demonstrated an extensive presence of viral antigen and a near absence of CD8-positive lymphocytes and natural killer cells, with marked expression of markers of apoptosis. Conclusions. Severe infantile RSV and influenza virus LRTI is characterized by inadequate (rather than excessive) adaptive immune responses, robust viral replication, and apoptotic crisis. [ABSTRACT FROM AUTHOR]

Purpose. Vancomycin dosages in overweight and obese children were evaluated. Methods. This retrospective study evaluated data for children who were age 2-17 years, received i.v. vancomycin, and were admitted to a children's hospital from September 1, 2007, through October 31, 2009. Patients were then stratified into two groups: normal-weight patients and overweight or obese patients. The primary objective was to compare the number of vancomycin regimens between groups with a trough concentration of 5-15 µg/mL. Secondary objectives included a comparison of dosage changes and toxicities. Multivariate, conditional logistic regression was performed to assess the relationship between attaining optimal vancomycin concentrations (5-15 µg/mL) and independent variables. Results. Data were collected for 232 courses of vancomycin, representing 187 patients. The mean ± S.D. initial dose for the normal-weight and overweight or obese groups differed significantly (461.3 ± 303.1 mg and 658.4 ± 389.6 mg, respectively; p < 0.01); the milligram-per-kilogram initial vancomycin dose did not. The multivariate analysis revealed that every-eight-hour regimens had increased odds of achieving therapeutic concentrations (p < 0.001), while obese children had decreased odds of achieving therapeutic concentrations (p = 0.037). Conclusion. A study of prescribing behavior in one hospital revealed no significant difference in the size of vancomycin doses (in milligrams per kilogram) given to normal-weight children compared with overweight or obese children. Regimens using every-eight-hour dosing were significantly more likely than other regimens to result in a vancomycin trough concentration of 5-15 µg/mL, and regimens for obese children, compared with regimens for nonobese children, were less likely to produce trough concentrations in the same range of 5-15 µg/mL. [ABSTRACT FROM AUTHOR]