Thirty-five children <2 years of age mechanically ventilated for respiratory syncytial virus (RSV) infection were randomized to receive an intravenous infusion of 15 mg/kg MEDI-493 or placebo. RSV concentration was measured in tracheal secretions by plaque assay before and at 24-h intervals after treatment. The reduction in tracheal RSV concentration from day 0 to day 1 (-1.7+/-0.28 vs. -0. 6+/-0.21 log10 pfu/mL; P=.004) and from day 0 to day 2 (-2.5+/-0.26 vs. -1.0+/-0.41 log10 pfu/mL; P=.012) was significantly greater in the MEDI-493 group than in the placebo group. RSV concentration in nasal aspirates did not differ significantly between the groups. No significant differences were observed in the tracheal aspirate white blood cell count, or myeloperoxidase or eosinophilic cationic protein concentration, or in measures of disease severity between the groups. Thus, treatment with 15 mg/kg MEDI-493 intravenously was well-tolerated and significantly reduced RSV concentration in tracheal aspirates of children with respiratory failure due to RSV.

Inflammatory mediators play a major role in the pathogenesis of respiratory syncytial virus (RSV) infection. The objective of this study was to evaluate the effect of i.v. dexamethasone on cytokine concentrations in tracheal aspirates (TA) of children with severe RSV disease and to correlate them with disease severity. Twenty-five cytokines were measured in TA obtained from children <2 yr old intubated for severe RSV disease, and enrolled in a double-blind study of i.v. dexamethasone (0.5 mg/kg; n = 22) vs. placebo (n = 19). Cytokine concentrations, measured at baseline and days 1 and 5 post-randomization using a multiplex assay, were compared within both treatment groups and correlated with: (i) tracheal white blood cell counts, (ii) tracheal RSV loads by culture and (iii) parameters of disease severity, including number of days of requirement for mechanical ventilation, intensive care unit (ICU), and hospitalization. At baseline interleukin (IL)-13 and IL-15 concentrations were significantly higher in the dexamethasone treatment group. On day 1 post-treatment, only MCP-1, eotaxin and IL-6 concentrations were significantly different but higher in the placebo group. On day 5: IL-13, IL-7, IL-8 and MIP-1alpha concentrations were higher in dexamethasone-treated patients. In both groups MIP-1beta inversely correlated with the days of ventilator support; MIP-1alpha, MIP-1beta and eotaxin inversely correlated with ICU days; and IL-6 inversely correlated with hospitalization regardless of the treatment assigned. Systemic administration of dexamethasone did not have a consistent effect on TA concentrations of pro-inflammatory cytokines. This may help explain, at least in part, the lack of clinical benefit of steroid treatment in children with severe RSV bronchiolitis.

We report a reduction in susceptibility to linezolid among Enterococcus isolates (98% in 2007 vs. 46% in 2014) in parallel with a 5-fold increase in linezolid use. A direct association could not be established as the majority of patients with linezolid nonsusceptible isolates did not have prior linezolid exposure. Nosocomial transmission of the nonsusceptible isolates could certainly have contributed.

Infection is a major cause of CSF shunt failure that places the patient at risk of intellectual impairment, development of loculated CSF compartments, and death. The purpose of this article is to review the published literature related to vancomycin for treatment of pediatric CSF shunt infections. Fifty percent of shunt infections appear within 2 months of shunt placement or revision; 90% occur within 6 months. Ninety percent of organisms infecting CSF shunting devices are Staphylococcus and Streptococcus species. The emergence of methicillin-resistant strains of staphylococci has made vancomycin the antibiotic of choice for these infections. The usual intravenous regimen is 60 mg/kg/day divided every 6 hours. Intraventricular vancomycin should be considered for most patients, starting with 10 mg daily. CSF vancomycin concentrations should be monitored and dosing adjustments made as needed to maintain CSF trough vancomycin concentrations between 5 and 20 mg/L.