SUMMARY Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS.

Palivizumab was licensed in June 1998 by the Food and Drug Administration for the reduction of serious lower respiratory tract infection caused by respiratory syncytial virus (RSV) in children at increased risk of severe disease. Since that time, the American Academy of Pediatrics has updated its guidance for the use of palivizumab 4 times as additional data became available to provide a better understanding of infants and young children at greatest risk of hospitalization attributable to RSV infection. The updated recommendations in this policy statement reflect new information regarding the seasonality of RSV circulation, palivizumab pharmacokinetics, the changing incidence of bronchiolitis hospitalizations, the effect of gestational age and other risk factors on RSV hospitalization rates, the mortality of children hospitalized with RSV infection, the effect of prophylaxis on wheezing, and palivizumab-resistant RSV isolates. This policy statement updates and replaces the recommendations found in the 2012 Red Book. Pediatrics 2014;134:415-420 Policy statements from the American Academy of Pediatrics (AAP) are designed to provide updated guidance for child health care topics, with an emphasis on evidence-based recommendations whenever possible. Policy statements are reviewed at least every 3 years and updated when appropriate. In following this procedure, the AAP Committee on Infectious Diseases (COID) has undertaken a systematic review of all recent and older peer-reviewed literature relating to the burden of respiratory syncytial virus (RSV) disease in infants and children, focusing on publications that delineate children at greatest risk of serious RSV disease and studies that define pharmacokinetics, safety, and efficacy. Detailed input regarding this guidance has been solicited from 21 committees, councils, sections, and advisory groups within the AAP, as well as organizations outside the AAP. Outside groups include the

Group B streptococci (GBS), a leading cause of neonatal sepsis and meningitis, are transferred to neonates from colonized mothers during childbirth. Prior studies using multilocus sequence typing (MLST) have found specific GBS clones (e.g., sequence type 17 [ST-17]) to be associated with neonatal disease in several geographic locations. Few population-based studies, however, have been conducted to determine the frequency of disease caused by specific GBS clones. MLST was used to assess the genetic diversity of 192 GBS strains from neonates and young children identified by population-based surveillance in Alberta, Canada, from 1993 to 2002. Comparisons were made to 232 GBS strains collected from colonized pregnant women, and all strains were characterized for one of nine capsule (cps) genotypes. A total of 47 STs were identified, and more than 80% of GBS strains were represented by 7 STs that have been shown to predominate in other populations. ST-17 and ST-19 were more prevalent in strains causing early onset disease (EOD) and late onset disease (LOD) than from pregnant women, whereas STs 1, 12, and 23 were more common in pregnant women. In addition, ST-17 strains and close relatives more frequently caused meningitis than sepsis and LOD versus EOD in this population of neonates. Further research is required to better understand why strains belonging to the ST-17 phylogenetic lineage are more likely to cause both LOD and meningitis and may provide clues into the pathogenesis of these conditions.

Guidance from the American Academy of Pediatrics (AAP) for the use of palivizumab prophylaxis against respiratory syncytial virus (RSV) was first published in a policy statement in 1998. Guidance initially was based on the result from a single randomized, placebo-controlled clinical trial conducted in 1996–1997 describing an overall reduction in RSV hospitalization rate from 10.6% among placebo recipients to 4.8% among children who received prophylaxis. The results of a second randomized, placebo-controlled trial of children with hemodynamically significant heart disease were published in 2003 and revealed a reduction in RSV hospitalization rate from 9.7% in control subjects to 5.3% among prophylaxis recipients. Because no additional controlled trials regarding efficacy were published, AAP guidance has been updated periodically to reflect the most recent literature regarding children at greatest risk of severe disease. Since the last update in 2012, new data have become available regarding the seasonality of RSV circulation, palivizumab pharmacokinetics, the changing incidence of bronchiolitis hospitalizations, the effects of gestational age and other risk factors on RSV hospitalization rates, the mortality of children hospitalized with RSV infection, and the effect of prophylaxis on wheezing and palivizumab-resistant RSV isolates. These data enable further refinement of AAP guidance to most clearly focus on those children at greatest risk.

Although most GBS-positive pregnant women were stably colonized during the peripartum period, we detected changes in capsule expression and recolonization with antigenically distinct GBS clones over time by applying MLST. Combining the epidemiologic and molecular typing data revealed host factors and clones associated with persistent colonization, as well as a clone that was more readily lost. This knowledge is useful for the development of prevention and intervention strategies to reduce the likelihood of maternal GBS colonization.

Enteroviruses are the major causes of aseptic meningitis. The major focus of diagnosis remains ruling out bacterial infection or confirming enteroviral etiology of infection. Properly implemented nucleic acid tests have the potential to reduce cost and unnecessary treatment.

One patient in 20 admitted to Calgary Health Region intensive care units acquires bloodstream infection and suffers longer intensive care unit stay and increased mortality rates. In our region, multiple antibiotic-resistant organisms are uncommon causes of bloodstream infections, suggesting that it may be safe to use narrower spectrum empirical treatment regimens than current guidelines recommend.

In a cohort study of 1207 pregnant women in Alberta, Canada, the serotype distributions of vaginal-rectal group B Streptococcus (GBS) isolates were compared with all isolates from neonates with invasive GBS disease identified by population-based surveillance. Serum concentrations of Ia, Ib, II, III, and V capsular polysaccharide (CPS)-specific IgG also were determined, according to serotype of the vaginal-rectal colonizing GBS strain. GBS colonization was detected in 19.5% (235 of 1207) of women. Serotype III accounted for 20.6% (48 of 233) of colonizing strains available for typing but for 37% (27 of 73) of invasive isolates from neonates (P<.01). Maternal colonization with type III was least likely to be associated with moderate concentrations of III CPS-specific IgG. Serotype III GBS is more invasive than other serotypes in this population; this may be due, at least in part, to poor maternal type III CPS-specific antibody response.