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1. David S. Kim, MD* 2. Abiara V. Agwu, MD* 3. Carol J. Baker, MD* 1. *Department of Pediatrics, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth), Houston, TX An 8-week-old male infant presents to the emergency department with 5 days of constipation and recent onset of fussiness, decreased feeding, and a swelling in the right neck. No temperature abnormalities are reported. The medical history is significant for preterm birth at 30 5/7 weeks’ gestation (weight, 930 g) via cesarean delivery due to preeclampsia and partial placental abruption to a 33-year-old mother with an unknown group B Streptococcus (GBS) status. During his neonatal admission he received antibiotics for 48 hours after delivery for a sepsis evaluation and topical ciprofloxacin, which resolved an episode of undefined otorrhea. After an otherwise uneventful hospital course, he was discharged at age 6 weeks. On examination in the emergency department, the vital signs are as follows: temperature, 97°F (36.1°C); heart rate, 172 beats/min; respirations, 40 breaths/min; blood pressure, 94/58 mm Hg; oxygen saturation, 100%; and weight, 2,400 g. The infant is in mild distress. An approximately 1-cm tender mass is palpable in the right submandibular region without overlying erythema. The remainder of the physical examination findings are normal. He has a total leukocyte count of 10,100/µL (10.1×109/L) with 20% bands. The basic metabolic panel and urinalysis findings are normal. Ultrasonography of the neck demonstrates symmetrical enlargement of numerous lymph nodes bilaterally, measuring up to 7 mm in the short axis, and without a drainable fluid collection (Fig). An abdominal radiograph is normal. Fig. Ultrasonography of the neck performed at presentation highlighting two of the numerous enlarged lymph nodes that were present bilaterally. The size and number of lymph nodes were increased for age. A fluid bolus improves the heart rate and capillary refill. A single dose of clindamycin is administered for a presumptive diagnosis of bacterial lymphadenitis. Because the infant now appears well, clindamycin is discontinued. Sixteen hours later, the infant has increasing …

Identified in the 1970s as the leading cause of invasive bacterial disease in neonates and young infants, group B Streptococcus (GBS) is now also recognized as a significant cause of morbidity and mortality among adults with underlying medical conditions and the elderly. Concomitant with the increasing incidence of GBS invasive disease in adults is the rise of resistance among GBS isolates to second line antibiotics. Previous research shows that among serotype V GBS, one of the most common capsular types causing adult invasive disease, sequence type 1 (ST1), accounts for an overwhelming majority of adult invasive disease isolates and frequently harbors macrolide resistance. In this study, using whole-genome sequencing data from strains isolated in the United States and Canada over a 45-year period, we examined the association of antimicrobial resistance with the emergence of invasive serotype V ST1 GBS. Our findings show a strong temporal association between increased macrolide resistance and the emergence of serotype V ST1 GBS subpopulations that currently co-circulate to cause invasive disease in adults and young infants. ST1 GBS subpopulations are defined, in part, by the presence of macrolide resistance genes in mobile genetic elements. Increased frequency of macrolide resistance-encoding mobile genetic elements among invasive GBS ST1 strains suggests the presence of such elements contributes to GBS virulence. Our work provides a foundation for the investigation of genetic features contributing to the increasing prevalence and pathogenesis of serotype V GBS in adult invasive disease.

Group B Streptococcus (GBS) is an asymptomatic colonizer of the female reproductive tract but can cause maternal and neonatal infections and adverse pregnancy outcomes. Here, we closed the genome sequence of strain CJB111, a neonatal GBS clinical isolate from a case of late-onset bacteremia without focus (Houston, TX; 1990).

Highlights • There is a major public health need for GBS vaccines for maternal immunization. • Important obstacles lie in the way of a pivotal clinical efficacy trial for licensure. • A vaccine development pathway based on an immune correlate of protection is envisaged. • Key considerations and priority activities for success are presented, based on WHO consultations., The development of a group B Streptococcus (GBS) vaccine for maternal immunization constitutes a global public health priority, to prevent GBS-associated early life invasive disease, stillbirth, premature birth, maternal sepsis, adverse neurodevelopmental consequences, and to reduce perinatal antibiotic use. Sample size requirements for the conduct of a randomized placebo-controlled trial to assess vaccine efficacy against the most relevant clinical endpoints, under conditions of appropriate ethical standards of care, constitute a significant obstacle on the pathway to vaccine availability. Alternatively, indirect evidence of protection based on immunologic data from vaccine and sero-epidemiological studies, complemented by data from opsonophagocytic in vitro assays and animal models, could be considered as pivotal data for licensure, with subsequent confirmation of effectiveness against disease outcomes in post-licensure evaluations. Based on discussions initiated by the World Health Organization we present key considerations about the potential role of correlates of protection towards an accelerated pathway for GBS vaccine licensure and wide scale use. Priority activities to support progress to regulatory and policy decision are outlined.

Background Group B Streptococcus (GBS) frequently colonizes pregnant women and can cause sepsis and meningitis in young infants. If colonization was prevented through maternal immunization, a reduction in perinatal GBS disease might be possible. A GBS type III capsular polysaccharide (CPS)-tetanus toxoid conjugate (III-TT) vaccine was evaluated for safety and efficacy in preventing acquisition of GBS colonization. Methods Healthy, nonpregnant women aged 18–40 years and screened to be GBS III vaginal and rectal culture negative were randomized to receive III-TT conjugate or tetanus diphtheria toxoid vaccine in a multicenter, observer-blinded trial. GBS vaginal and rectal cultures and blood were obtained bimonthly over 18 months. Serum concentrations of GBS III CPS-specific antibodies were determined using enzyme-linked immunosorbent assay. Results Among 1525 women screened, 650 were eligible for the intent-to-treat analysis. For time to first acquisition of vaginal GBS III, vaccine efficacy was 36% (95% confidence interval [CI], 1%–58%; P = .044), and for first rectal acquisition efficacy was 43% (95% CI, 11% to 63%; P = .014). Two months post-immunization, geometric mean concentrations of serum GBS type III CPS-specific immunoglobulin G were 12.6 µg/mL (95% CI, 9.95 to 15.81) in GBS III-TT recipients, representing a 4-fold increase from baseline in 95% of women, which persisted. Both vaccines were well tolerated. Conclusions GBS CPS III-TT conjugate vaccine significantly delayed acquisition of vaginal and rectal GBS III colonization. In addition to its use for maternal immunization to passively protect infants with maternally derived antibodies, a multivalent vaccine might also serve to reduce fetal and neonatal exposure to GBS. Clinical Trials Registration NCT00128219.

Importance Immunization with tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in the United States during weeks 27 through 36 of pregnancy to prevent life-threatening infant pertussis. The optimal gestation for immunization to maximize concentrations of neonatal pertussis toxin antibodies is unknown. Objective To determine pertussis toxin antibody concentrations in cord blood from neonates born to women immunized and unimmunized with Tdap vaccine in pregnancy and optimal gestational age for immunization to maximize concentrations of neonatal antibodies. Design, Setting, and Participants Prospective, observational, cohort study of term neonates in Houston, Texas (December 2013-March 2014). Exposures Tdap immunization during weeks 27 through 36 of pregnancy or no Tdap immunization. Main Outcomes and Measures Primary outcome was geometric mean concentrations (GMCs) of pertussis toxin antibodies in cord blood of Tdap-exposed and Tdap-unexposed neonates and proportions of Tdap-exposed and Tdap-unexposed neonates with pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher, cutoffs representing quantifiable antibodies or levels that may be protective until the infant immunization series begins. Secondary outcome was the optimal gestation for immunization to achieve maximum pertussis toxin antibodies. Results Six hundred twenty-six pregnancies (mean maternal age, 29.7 years; 41% white, 27% Hispanic, 26% black, 5% Asian, 1% other; mean gestation, 39.4 weeks) were included. Three hundred twelve women received Tdap vaccine at a mean gestation of 31.2 weeks (range, 27.3-36.4); 314 were unimmunized. GMC of neonatal cord pertussis toxin antibodies from the Tdap-exposed group was 47.3 IU/mL (95% CI, 42.1-53.2) compared with 12.9 IU/mL (95% CI, 11.7-14.3) in the Tdap-unexposed group, for a GMC ratio of 3.6 (95% CI, 3.1-4.2;P Conclusions and Relevance Immunization with Tdap vaccine during the third trimester of pregnancy, compared with no immunization, was associated with higher neonatal concentrations of pertussis toxin antibodies. Immunization early in the third trimester was associated with the highest concentrations.

Complications of preterm birth are the leading cause of deaths in children aged, Background Preterm birth complications are the leading cause of deaths among children

Background Early-onset group B streptococcal disease (EOGBS) occurs in neonates (days 0–6) born to pregnant women who are rectovaginally colonized with group B Streptococcus (GBS), but the risk of EOGBS from vertical transmission has not been systematically reviewed. This article, the seventh in a series on the burden of GBS disease, aims to estimate this risk and how it varies with coverage of intrapartum antibiotic prophylaxis (IAP), used to reduce the incidence of EOGBS. Methods We conducted systematic reviews (Pubmed/Medline, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups on maternal GBS colonization and neonatal outcomes. We included articles with ≥200 GBS colonized pregnant women that reported IAP coverage. We did meta-analyses to determine pooled estimates of risk of EOGBS, and examined the association in risk of EOGBS with IAP coverage. Results We identified 30 articles including 20328 GBS-colonized pregnant women for inclusion. The risk of EOGBS in settings without an IAP policy was 1.1% (95% confidence interval [CI], .6%–1.5%). As IAP increased, the risk of EOGBS decreased, with a linear association. Based on linear regression, the risk of EOGBS in settings with 80% IAP coverage was predicted to be 0.3% (95% CI, 0–.9). Conclusions The risk of EOGBS among GBS-colonized pregnant women, from this first systematic review, is consistent with previous estimates from single studies (1%–2%). Increasing IAP coverage was linearly associated with decreased risk of EOGBS disease.

Background Neonatal encephalopathy (NE) is a leading cause of child mortality and longer-term impairment. Infection can sensitize the newborn brain to injury; however, the role of group B streptococcal (GBS) disease has not been reviewed. This paper is the ninth in an 11-article series estimating the burden of GBS disease; here we aim to assess the proportion of GBS in NE cases. Methods We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups reporting GBS-associated NE. Meta-analyses estimated the proportion of GBS disease in NE and mortality risk. UK population-level data estimated the incidence of GBS-associated NE. Results Four published and 25 unpublished datasets were identified from 13 countries (N = 10436). The proportion of NE associated with GBS was 0.58% (95% confidence interval [CI], 0.18%–.98%). Mortality was significantly increased in GBS-associated NE vs NE alone (risk ratio, 2.07 [95% CI, 1.47–2.91]). This equates to a UK incidence of GBS-associated NE of 0.019 per 1000 live births. Conclusions The consistent increased proportion of GBS disease in NE and significant increased risk of mortality provides evidence that GBS infection contributes to NE. Increased information regarding this and other organisms is important to inform interventions, especially in low- and middle-resource contexts.

Many healthcare providers are not familiar with the Food and Drug Administration (FDA) vaccine licensure process, the Advisory Committee on Immunization Practices (ACIP) vaccine recommendation process, and how FDA vaccine licensure and ACIP recommendations are related. Vaccines for use in the United States military and civilian populations are licensed by the FDA by several potential pathways but use of licensed vaccines in the civilian population should be based on recommendations made by the ACIP. In performing these distinct activities, FDA and ACIP function under different mandates. In this article, we discuss whether the FDA licensure pathways used to approve a vaccine impacts ACIP recommendation categories for vaccines licensed from 2006 to 2016.

Hypervirulent disease due to group A Streptococcus (GAS) can result from strains with mutations that enhance virulence gene expression but reduce subsequent transmission. We used whole-genome sequencing to investigate intrafamilial spread among 4 siblings of infection due to a hypervirulent GAS strain that resulted in a fatality. All invasive and pharyngeal GAS isolates had an identical mutation in a gene encoding a key regulatory protein that yielded a hyperinvasive phenotype. These data challenge the prevailing theory of reduced transmission induced by mutations that lead to hypervirulent GAS by showing that spread of hypervirulent GAS may lead to clusters of invasive disease.

Background Kinetics of Tdap-induced maternally-derived antibodies in infants are poorly understood. Pre-Tdap era data suggest that maternal pertussis antibodies in infants have a half-life of approximately 5–6 weeks. Methods 34 mother-infant pairs had blood collected before maternal Tdap vaccination, 4 weeks later, at delivery (maternal and cord), and at infant ages 3 and 6 weeks from June 2014-March 2015. Immunoglobulin G (IgG) to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbrial proteins (FIM) and pertactin (PRN) was quantified by multiplex luminex assay (IU/ml). Geometric mean concentrations (GMCs) with 95% confidence intervals (C.I.) and half-life of pertussis antibodies were calculated. Results Tdap was administered to 34 women (mean age 31.1 years) at mean gestation 30.7 weeks (28–32.7). Mean neonatal gestation was 39.1 weeks (36–41.1) and mean birthweight was 3379 g (2580–4584). Four weeks post-Tdap vaccination, maternal pertussis-specific IgG GMCs increased ≥4-fold in 59%, 41%, 29% and 44% of women for PT, FHA, FIM and PRN, respectively, and then waned. The transplacental transport ratio of pertussis antibodies was 1.35 for PT, 1.41 for FHA, 1.31 for FIM and 1.36 for PRN. Between birth and age 6 weeks, infant serum GMC for PT-specific IgG decreased from 55.1 IU/mL (38.6–78.6) to 21.1 IU/ml (14.7–30.2), and the proportion of infants with PT levels ≥10 IU/ml fell from 97% to 67%. Half-life of pertussis-specific IgG in infants in days was 29.4 (95% CI 27.3–31.7) for PT, 29.8 (95% CI 27.7–32.2) for FHA, 31.2 (95% CI 28.9–33.7) for PRN, and 35.8 (95% CI 30.1–44.3) for FIM. Conclusion The half-life of pertussis-specific antibodies in infants induced by maternal Tdap vaccination (29–36 days) is shorter than previously reported. Understanding how the durability of passively-acquired antibodies impacts infant susceptibility to pertussis and response to primary vaccination is critical to refine prevention strategies.

Group B Streptococcus (GBS) is an important cause of disease in young infants, stillbirths, pregnant and post-partum women. GBS vaccines for maternal immunization are in development aiming to reduce this burden. Standardisation of case definitions and ascertainment methodologies for GBS disease is needed to support future trials of maternal GBS vaccines. Considerations presented here may also serve to promote consistency in observational studies and surveillance, to better establish disease burden. The World Health Organization convened a working group to provide consensus guidance for case ascertainment and case definitions of GBS disease in stillbirths, infants, pregnant and post-partum women, with feedback sought from external stakeholders. In intervention studies, case capture and case ascertainment for GBS disease should be based on antenatal recruitment of women, with active follow-up, systematic clinical assessment, standardised sampling strategies and optimised laboratory methods. Confirmed cases of invasive GBS disease in stillbirths or infants should be included in a primary composite endpoint for vaccine efficacy studies, with GBS cultured from a usually sterile body site (may be post-mortem). For additional endpoints, or observational studies, confirmed cases of GBS sepsis in pregnant and post-partum women should be assessed. Culture independent diagnostic tests (CIDTs) may detect additional presumed cases, however, the use of these diagnostics needs further evaluation. Efficacy of vaccination against maternal and neonatal GBS colonisation, and maternal GBS urinary tract infection could be included as additional, separate, endpoints and/or in observational studies. Whilst the focus here is on specific GBS disease outcomes, intervention studies also present an opportunity to establish the contribution of GBS across adverse perinatal outcomes, including all-cause stillbirth, preterm birth and neonatal encephalopathy.

Group B streptococcus (GBS) is a leading cause of young infant mortality and morbidity globally, with vaccines being developed for over four decades but none licensed to date. A serocorrelate of protection against invasive disease in young infants is being considered to facilitate vaccine early licensure, followed by demonstration of efficacy assessed postlicensure. In this Review, we synthesise the available scientific evidence to define an immune correlate associated with GBS disease risk reduction on the basis of studies of natural infection. We summarise studies that have investigated GBS serum anticapsular or anti-protein antibodies, and studies measuring the association between antibody function and disease risk reduction. We highlight how knowledge on the development of correlates of protection from existing vaccines could be harnessed to facilitate GBS vaccine development. These lessons include aggregation of serocorrelates of protection for individual serotypes, understanding the relationship between immunity derived from natural exposure of adults and vaccine-induced immunity, or using extrapolation of protection from in-vitro immunoassay results. We also highlight key considerations for the assessment of the role of antibodies to derive a serocorrelate of risk reduction in future seroepidemiological studies of GBS disease.

OBJECTIVES: The presence of methicillin-resistant Staphylococcus aureus (MRSA) in cystic fibrosis (CF) patients' sputa is associated with a decline in pulmonary function and increased mortality. Vancomycin is the preferred treatment for MRSA pneumonia in children. No published studies have evaluated the vancomycin dose needed to achieve goal vancomycin trough concentrations (VTCs; 15–20 mg/L) in pediatric patients with CF. The primary objective is to determine whether a vancomycin dosage of 60 mg/kg/day achieves a goal VTC in pediatric CF patients. Secondary objectives include determining the average dosage required to reach a goal VTC and the impact of achieving a goal VTC on estimated glomerular filtration rate (eGFR) and pulmonary function. METHODS: A retrospective review of pediatric patients with CF who received vancomycin was conducted. RESULTS: A total of 90 vancomycin treatment courses were analyzed. Standard vancomycin dosing (60 mg/kg/day) achieved goal VTC in 11 courses (12.2%). The mean dosage required to achieve a goal VTC for all courses was 70.6 ± 16.7 mg/kg/day. Patients who achieved goal VTCs were more often older, weighed more, and had higher serum creatinine concentrations at therapy initiation. On average, a dosage of 70.6 mg/kg/day was required to achieve a goal VTC. Despite dosages up to 120 mg/kg/day, no significant changes in renal function occurred. Achieving a goal VTC had no significant impact on eGFR or pulmonary function during therapy. CONCLUSIONS: Vancomycin dosing of 60 mg/kg/day does not reliably achieve a VTC of 15 to 20 mg/L in pediatric CF patients. Younger CF patients may require higher vancomycin doses.

Background Acellular pertussis (aP) vaccines replaced whole cell pertussis (wP) vaccines for the recommended childhood primary series in the United States in 1997. As women primed with aP vaccines in childhood enter reproductive age, it is unknown how maternal aP-priming will impact pertussis protection conferred to infants through Tdap (tetanus toxoid, reduced diphtheria toxoid and acellular pertussis) vaccination during pregnancy. Methods Infants born at term to women who had been vaccinated with Tdap at 27-36 weeks’ gestation and ≥ 14 days prior to delivery were included. Geometric mean concentrations (GMC) of pertussis-specific antibodies (measured in IU/mL) in umbilical cord blood of infants born to women born after 1997 (aP vaccine primed) were compared with those born to women born before 1992 (wP vaccine primed). Results 253 and 506 neonates born to aP- and wP-primed women, respectively, were included. Compared with wP-primed women, aP-primed women were younger (19.3 v. 24.5 years), more likely to be Hispanic or non-Hispanic black and to have infants with lower birthweight (3264 v. 3392 grams, p< 0.01 for all). Gestation at Tdap receipt, gestational age at delivery, and interval between Tdap administration and delivery were not statistically different. Antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) were significantly lower among neonates born to aP-primed versus wP-primed mothers (PT: 17.3 v. 36.4, GMC ratio 0.475 (0.408 – 0.552) (Figure); FHA: 104.6 v. 121.4, GMC ratio 0.861 (0.776 – 0.958)). No significant differences were observed between the aP and wP-primed groups for anti- fimbriae (FIM) or anti-pertactin (PRN) antibodies ((FIM: 469.6 v. 577.2, GMC ratio 0.81 (CI 0.65 – 1.01); PRN 338.8 v. 292.6, GMC ratio 1.16 (CI 0.99 – 1.35)). Figure. Distribution of anti-PT antibody levels in cord blood in infants born to women who were primed with whole cell pertussis compared with acellular pertussis vaccines in childhood.* Conclusion The type of pertussis vaccine a woman received during childhood significantly impacted her response to Tdap vaccination during pregnancy; the largest reduction was in anti-PT antibodies thought to be most important in preventing severe infection in infants. These findings suggest that infants born to aP-primed women who received Tdap during pregnancy may have less passive protection against pertussis during the first months of life than those born to wP-primed women. Disclosures All Authors: No reported disclosures

Importance Early-onset sepsis (EOS) remains a potentially fatal newborn condition. Ongoing surveillance is critical to optimize prevention and treatment strategies. Objective To describe the current incidence, microbiology, morbidity, and mortality of EOS among a cohort of term and preterm infants. Design, setting, and participants This prospective surveillance study included a cohort of infants born at a gestational age (GA) of at least 22 weeks and birth weight of greater than 400 g from 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from April 1, 2015, to March 31, 2017. Data were analyzed from June 14, 2019, to January 28, 2020. Main outcomes and measures Early-onset sepsis defined by isolation of pathogenic species from blood or cerebrospinal fluid culture within 72 hours of birth and antibiotic treatment for at least 5 days or until death. Results A total of 235 EOS cases (127 male [54.0%]) were identified among 217 480 newborns (1.08 [95% CI, 0.95-1.23] cases per 1000 live births). Incidence varied significantly by GA and was highest among infants with a GA of 22 to 28 weeks (18.47 [95% CI, 14.57-23.38] cases per 1000). No significant differences in EOS incidence were observed by sex, race, or ethnicity. The most frequent pathogens were Escherichia coli (86 [36.6%]) and group B streptococcus (GBS; 71 [30.2%]). E coli disease primarily occurred among preterm infants (68 of 131 [51.9%]); GBS disease primarily occurred among term infants (54 of 104 [51.9%]), with 24 of 45 GBS cases (53.3%) seen in infants born to mothers with negative GBS screening test results. Intrapartum antibiotics were administered to 162 mothers (68.9%; 110 of 131 [84.0%] preterm and 52 of 104 [50.0%] term), most commonly for suspected chorioamnionitis. Neonatal empirical antibiotic treatment most frequently included ampicillin and gentamicin. All GBS isolates were tested, but only 18 of 81 (22.2%) E coli isolates tested were susceptible to ampicillin; 6 of 77 E coli isolates (7.8%) were resistant to both ampicillin and gentamicin. Nearly all newborns with EOS (220 of 235 [93.6%]) displayed signs of illness within 72 hours of birth. Death occurred in 38 of 131 infected infants with GA of less than 37 weeks (29.0%); no term infants died. Compared with earlier surveillance (2006-2009), the rate of E coli infection increased among very low-birth-weight (401-1500 g) infants (8.68 [95% CI, 6.50-11.60] vs 5.07 [95% CI, 3.93-6.53] per 1000 live births; P = .008). Conclusions and relevance In this study, EOS incidence and associated mortality disproportionately occurred in preterm infants. Contemporary cases have demonstrated the limitations of current GBS prevention strategies. The increase in E coli infections among very low-birth-weight infants warrants continued study. Ampicillin and gentamicin remained effective antibiotics in most cases, but ongoing surveillance should monitor antibiotic susceptibilities of EOS pathogens.

The molecular mechanisms underlying pathogen emergence in humans is a critical but poorly understood area of microbiologic investigation. Serotype V group B Streptococcus (GBS) was first isolated from humans in 1975, and rates of invasive serotype V GBS disease significantly increased starting in the early 1990s. We found that 210 of 229 serotype V GBS strains (92%) isolated from the bloodstream of nonpregnant adults in the United States and Canada between 1992 and 2013 were multilocus sequence type (ST) 1. Elucidation of the complete genome of a 1992 ST-1 strain revealed that this strain had the highest homology with a GBS strain causing cow mastitis and that the 1992 ST-1 strain differed from serotype V strains isolated in the late 1970s by acquisition of cell surface proteins and antimicrobial resistance determinants. Whole-genome comparison of 202 invasive ST-1 strains detected significant recombination in only eight strains. The remaining 194 strains differed by an average of 97 SNPs. Phylogenetic analysis revealed a temporally dependent mode of genetic diversification consistent with the emergence in the 1990s of ST-1 GBS as major agents of human disease. Thirty-one loci were identified as being under positive selective pressure, and mutations at loci encoding polysaccharide capsule production proteins, regulators of pilus expression, and two-component gene regulatory systems were shown to affect the bacterial phenotype. These data reveal that phenotypic diversity among ST-1 GBS is mainly driven by small genetic changes rather than extensive recombination, thereby extending knowledge into how pathogens adapt to humans.

Group B Streptococcus (GBS) is associated with invasive disease in utero and stillbirth. We estimated that 1% of all stillbirths in developed countries and 4% in Africa were associated with GBS., Background There are an estimated 2.6 million stillbirths each year, many of which are due to infections, especially in low- and middle-income contexts. This paper, the eighth in a series on the burden of group B streptococcal (GBS) disease, aims to estimate the percentage of stillbirths associated with GBS disease. Methods We conducted systematic literature reviews (PubMed/Medline, Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde, World Health Organization Library Information System, and Scopus) and sought unpublished data from investigator groups. Studies were included if they reported original data on stillbirths (predominantly ≥28 weeks’ gestation or ≥1000 g, with GBS isolated from a sterile site) as a percentage of total stillbirths. We did meta-analyses to derive pooled estimates of the percentage of GBS-associated stillbirths, regionally and worldwide for recent datasets. Results We included 14 studies from any period, 5 with recent data (after 2000). There were no data from Asia. We estimated that 1% (95% confidence interval [CI], 0–2%) of all stillbirths in developed countries and 4% (95% CI, 2%–6%) in Africa were associated with GBS. Conclusions GBS is likely an important cause of stillbirth, especially in Africa. However, data are limited in terms of geographic spread, with no data from Asia, and cases worldwide are probably underestimated due to incomplete case ascertainment. More data, using standardized, systematic methods, are critical, particularly from low- and middle-income contexts where the highest burden of stillbirths occurs. These data are essential to inform interventions, such as maternal GBS vaccination.

Group B Streptococcus is associated with multiple adverse pregnancy outcomes, yet previous epidemiology and interventions have mainly focused on neonatal invasive disease in high-income settings. We describe the rationale and approach for the first worldwide estimates of all relevant outcomes., Improving maternal, newborn, and child health is central to Sustainable Development Goal targets for 2030, requiring acceleration especially to prevent 5.6 million deaths around the time of birth. Infections contribute to this burden, but etiological data are limited. Group B Streptococcus (GBS) is an important perinatal pathogen, although previously focus has been primarily on liveborn children, especially early-onset disease. In this first of an 11-article supplement, we discuss the following: (1) Why estimate the worldwide burden of GBS disease? (2) What outcomes of GBS in pregnancy should be included? (3) What data and epidemiological parameters are required? (4) What methods and models can be used to transparently estimate this burden of GBS? (5) What are the challenges with available data? and (6) How can estimates address data gaps to better inform GBS interventions including maternal immunization? We review all available GBS data worldwide, including maternal GBS colonization, risk of neonatal disease (with/without intrapartum antibiotic prophylaxis), maternal GBS disease, neonatal/infant GBS disease, and subsequent impairment, plus GBS-associated stillbirth, preterm birth, and neonatal encephalopathy. We summarize our methods for searches, meta-analyses, and modeling including a compartmental model. Our approach is consistent with the World Health Organization (WHO) Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER), published in The Lancet and the Public Library of Science (PLoS). We aim to address priority epidemiological gaps highlighted by WHO to inform potential maternal vaccination.

Group B Streptococcus is an important cause of disease in pregnant women, stillbirth, and infants. These first estimates show the magnitude and the potential impact of maternal vaccination., Background We aimed to provide the first comprehensive estimates of the burden of group B Streptococcus (GBS), including invasive disease in pregnant and postpartum women, fetal infection/stillbirth, and infants. Intrapartum antibiotic prophylaxis is the current mainstay of prevention, reducing early-onset infant disease in high-income contexts. Maternal GBS vaccines are in development. Methods For 2015 live births, we used a compartmental model to estimate (1) exposure to maternal GBS colonization, (2) cases of infant invasive GBS disease, (3) deaths, and (4) disabilities. We applied incidence or prevalence data to estimate cases of maternal and fetal infection/stillbirth, and infants with invasive GBS disease presenting with neonatal encephalopathy. We applied risk ratios to estimate numbers of preterm births attributable to GBS. Uncertainty was also estimated. Results Worldwide in 2015, we estimated 205000 (uncertainty range [UR], 101000–327000) infants with early-onset disease and 114000 (UR, 44000–326000) with late-onset disease, of whom a minimum of 7000 (UR, 0–19000) presented with neonatal encephalopathy. There were 90000 (UR, 36000–169000) deaths in infants

There is heterogeneity in intrapartum antibiotic use and implementation of policy varies widely. Global strategies to enhance the prevention of group B streptococcal disease that may include maternal vaccination are needed., Background Intrapartum antibiotic chemoprophylaxis (IAP) prevents most early-onset group B streptococcal (GBS) disease. However, there is no description of how IAP is used around the world. This article is the sixth in a series estimating the burden of GBS disease. Here we aimed to review GBS screening policies and IAP implementation worldwide. Methods We identified data through (1) systematic literature reviews (PubMed/Medline, Embase, Literature in the Health Sciences in Latin America and the Caribbean [LILACS], World Health Organization library database [WHOLIS], and Scopus) and unpublished data from professional societies and (2) an online survey and searches of policies from medical societies and professionals. We included data on whether an IAP policy was in use, and if so whether it was based on microbiological or clinical risk factors and how these were applied, as well as the estimated coverage (percentage of women receiving IAP where indicated). Results We received policy information from 95 of 195 (49%) countries. Of these, 60 of 95 (63%) had an IAP policy; 35 of 60 (58%) used microbiological screening, 25 of 60 (42%) used clinical risk factors. Two of 15 (13%) low-income, 4 of 16 (25%) lower-middle–income, 14 of 20 (70%) upper-middle–income, and 40 of 44 (91%) high-income countries had any IAP policy. The remaining 35 of 95 (37%) had no national policy (25/33 from low-income and lower-middle–income countries). Coverage varied considerably; for microbiological screening, median coverage was 80% (range, 20%–95%); for clinical risk factor–based screening, coverage was 29% (range, 10%–50%). Although there were differences in the microbiological screening methods employed, the individual clinical risk factors used were similar. Conclusions There is considerable heterogeneity in IAP screening policies and coverage worldwide. Alternative global strategies, such as maternal vaccination, are needed to enhance the scope of global prevention of GBS disease.

Background Maternal rectovaginal colonization with group B Streptococcus (GBS) is the most common pathway for GBS disease in mother, fetus, and newborn. This article, the second in a series estimating the burden of GBS, aims to determine the prevalence and serotype distribution of GBS colonizing pregnant women worldwide. Methods We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus), organized Chinese language searches, and sought unpublished data from investigator groups. We applied broad inclusion criteria to maximize data inputs, particularly from low- and middle-income contexts, and then applied new meta-analyses to adjust for studies with less-sensitive sampling and laboratory techniques. We undertook meta-analyses to derive pooled estimates of maternal GBS colonization prevalence at national and regional levels. Results The dataset regarding colonization included 390 articles, 85 countries, and a total of 299924 pregnant women. Our adjusted estimate for maternal GBS colonization worldwide was 18% (95% confidence interval [CI], 17%–19%), with regional variation (11%–35%), and lower prevalence in Southern Asia (12.5% [95% CI, 10%–15%]) and Eastern Asia (11% [95% CI, 10%–12%]). Bacterial serotypes I–V account for 98% of identified colonizing GBS isolates worldwide. Serotype III, associated with invasive disease, accounts for 25% (95% CI, 23%–28%), but is less frequent in some South American and Asian countries. Serotypes VI–IX are more common in Asia. Conclusions GBS colonizes pregnant women worldwide, but prevalence and serotype distribution vary, even after adjusting for laboratory methods. Lower GBS maternal colonization prevalence, with less serotype III, may help to explain lower GBS disease incidence in regions such as Asia. High prevalence worldwide, and more serotype data, are relevant to prevention efforts.

Group B streptococcal rectovaginal colonization prevalence in women of Indian descent living in the United States was 24.7% comparable with US rates but higher than rates reported from India. The capsular polysaccharide types were distinct in that type V was most common and 33% of group B streptococcal strains were nontypeable.

Group B streptococcus and respiratory syncytial virus are leading causes of infant morbidity and mortality worldwide. No licensed vaccines are available for either disease, but vaccines for both are under development. Severe respiratory syncytial virus disease can be prevented by passively administered antibody. The presence of maternal IgG antibody specific to respiratory syncytial virus is associated with reduced prevalence and severity of respiratory syncytial virus disease in the first few weeks of life, whereas maternal serotype-specific anticapsular antibody is associated with protection against both early-onset and late-onset group B streptococcus disease. Therefore, vaccination in pregnancy might protect infants against both diseases. This report describes what is known about immune protection against group B streptococcus and respiratory syncytial virus, identifies knowledge gaps regarding the immunobiology of both diseases, and aims to prioritise research directions in maternal immunisation.

Recent outbreaks of serogroup B invasive meningococcal disease on US college campuses have heightened awareness about the gap in available vaccines to protect against this serious and sometimes fatal infection. Federal agencies, college health authorities, public health officials, and consum

Group B protective surface protein (BPS) is expressed on the cell surface of some group B streptococcal (GBS) (Streptococcus agalactiae) strains and adds to the identification by capsular polysaccharide (CPS), and c or R proteins. We investigated the prevalence of BPS among GBS clinical isolates (303 invasive, 4122 colonizing) collected over 11 years in four American cities. Hot HCl cell extracts were tested by immunoprecipitation in agarose with rabbit antisera to BPS; the alpha (α) and beta (β) components of c protein; R1, R3, and R4 species of R protein; and CPS serotypes Ia-VIII. BPS was found in 155 isolates (seven invasive, 148 colonizing). Of these, 87 were Ia, 37 II, 20 V; none were III. BPS was expressed usually with another protein: a species of R by 87 or a component of c by 39. The predominant CPS/protein profiles with BPS were Ia/R1,BPS and II/c(α + β),BPS. Thus, along with CPS serotype and other surface proteins, BPS can be a valuable marker for precise strain characterization of unique GBS clinical isolates with complex surface protein profiles.

BACKGROUND: Little is known about duration of protection after the infant primary series of hepatitis B (HB) vaccine in settings of low HB endemicity. This study sought to determine the proportion of adolescents immunized as infants who had protective titers of antibody to hepatitis B surface antigen (anti-HBs) before and after a challenge dose of vaccine. METHODS: US-born 16- through 19-year-olds who received a recombinant HB vaccine 3-dose series initiated within 7 days of birth (group 1) or at ≥4 weeks of age (group 2) and completed by 12 months of age were enrolled. Participants had serologic testing before and 2 weeks after randomization to receive a challenge dose of 10 µg or 20 µg of Engerix-B. Baseline and postchallenge levels of anti-HBs were compared by group, challenge dosage, and demographic and behavioral characteristics. RESULTS: At baseline, 24% had protective anti-HBs levels of ≥10 IU/mL; 92% achieved protective levels after challenge dose. Although group 1 had a lower proportion of seroprotection at baseline, group and challenge dosage were not associated with postchallenge proportion of seroprotection. Being in group 2, higher test dosage, higher baseline geometric mean titer, and nonwhite race were associated with significantly higher geometric mean titer after challenge dose. CONCLUSIONS: More than 90% of study participants immunized against HB as infants exhibited a seroprotective response to a challenge dose of vaccine. Duration of protection from the primary infant HB vaccine series extended through the adolescent years in the setting of low HB endemicity.

Background Maternal immunization with tetanus, diphtheria, acellular pertussis vaccine (Tdap) in the third trimester reduces infant pertussis, but data are lacking on how this strategy impacts pertussis antibody levels in large cohorts of preterm infants Methods We collected paired maternal delivery-cord sera from infants of women who received Tdap ≥7 days before birth. IgG to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbrial proteins (FIM) and pertactin (PRN) was quantified by Luminex assay (IU/mL). Geometric mean concentrations (GMC) with 95% confidence intervals (CI) for pertussis antibodies were calculated. Four infant groups were compared by weeks of gestation: very ( Results 344 preterm and 688 term mother-infant pairs were included. Among preterm infants, mean maternal age was 31.2 years (range 15.1–39.3); 37% were white, 37% Hispanic, 17% Black, 8% Asian and 1% other. Fifty-six were very preterm infants (16%, mean gestation 30.5 weeks), 82 moderate (24%, 33.1 weeks), and 206 late (60%, 35.4 weeks); 17 (5%) were born at Conclusion Although levels are lower than in term infants, maternal immunization with Tdap results in substantial pertussis-specific antibodies in most preterm infants, especially late preterm infants. Disclosures All Authors: No reported Disclosures.

Background Since 1970 group B Streptococcus (GBS) has been a frequent cause of sepsis or meningitis in young infants. Capsular polysaccharide type V was first recognized in 1990 and has increased to the point where it now causes ~15% of GBS infections. GBS type V strains are almost entirely sequence type 1 (ST1) in adult infections. To understand the emergence of type V GBS, we compared infant strains before 1990 to more contemporary isolates from young infants and adults. Methods Thirty-five strains isolated from blood or CSF of infants Results The majority (29/35) of Houston young infant strains were ST1. Type V GBS strains isolated prior to 1990 were more likely to be of ST-2 or ST-26 (5/10) compared with those from 1990 or later (24/25 and 14/14 CDC infant invasive type V). Tetracycline resistance was identified in 83% (29/35) while macrolide resistance (MR) occurred in only 23% (8/35) of the strains. Compared with early neonatal isolates, MR was significantly more frequent among contemporary neonatal (12/14, 86%, P < 0.0001) and adult (502/710, 71%, P < 0.0001) ST1 GBS. Phylogenetic analysis showed two distinct clades defined, in part, by MR. A high-frequency MR (340/360, 94%) clade was defined by the presence of erm(B) on Tn3872 while the low-frequency MR clade (159/350, 45%) was more diverse in mobile elements contributing to MR. The majority (27/29) of early neonatal ST1 GBS strains were observed in the low-frequency MR clade. Conclusion Infant invasive disease due to type V GBS before 1990 consisted of more diverse STs but is now almost exclusively ST1. Differences in the frequency of MR between early neonatal and contemporary type V ST1 GBS suggest MR may, at least in part, have driven the expansion of type V ST1 GBS. Disclosures All Authors: No reported Disclosures.

Background. Further reduction in the group B streptococcal (GBS) disease burden in neonates in the United States awaits an additional prevention strategy, such as maternal immunization. Methods. We performed a prospective, multicenter, case-control study of 33 mothers delivering neonates with early onset GBS infection (cases), and 99 age- and ethnicity-matched mothers colonized with the same capsular polysaccharide (CPS) types delivering healthy neonates (controls). Relative risk and absolute risk were calculated for early onset disease associated with concentrations of type Ia, III, or V CPS-specific antibody in maternal serum. Results. For GBS types Ia and III, maternal CPS–specific antibody concentrations of ≥0.5 µg/mL were associated with a relative risk of approximately 0.1 (95% confidence intervals [CIs], .01–.74 and 0–.72, respectively; P = .02 for each), corresponding to a 90% risk reduction (by logistic regression). For type V, the relative risk was 0.3 (95% CI, .01–3.1), corresponding to a 70% risk reduction. By Bayesian modeling, the risk of early onset disease would decrease by 70% if maternal CPS-specific antibody concentrations for these 3 GBS types were ≥1 µg/mL. Conclusions. Maternal CPS-specific antibody serum concentrations of ≥1 μg/mL at the time of delivery appear to protect most neonates from early onset GBS type Ia and III disease.

Background. We assessed vaccine effectiveness (VE) for RotaTeq (RV5; 3 doses) and Rotarix (RV1; 2 doses) at reducing rotavirus acute gastroenteritis (AGE) inpatient and emergency department (ED) visits in US children. Methods. We enrolled children

Group B Streptococcus (GBS) is a leading cause of invasive disease in infants, causing mortality and neurodevelopmental impairment (NDI) in survivors. This article estimates the percentage of survivors of infant GBS disease with NDI., Background Survivors of infant group B streptococcal (GBS) disease are at risk of neurodevelopmental impairment (NDI), a burden not previously systematically quantified. This is the 10th of 11 articles estimating the burden of GBS disease. Here we aimed to estimate NDI in survivors of infant GBS disease. Methods We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data on the risk of NDI after invasive GBS disease in infants

Background Trichosporonosis is an emerging and often fatal opportunistic fungal infection in immunocompromised patients, particularly those with hematologic malignancy, but data in children are lacking. Methods We report here 3 cases of invasive infection caused by Trichosporon asahii in pediatric patients with acute lymphoblastic leukemia at Texas Children's Hospital in Houston, Texas. We also conducted a literature review and identified 16 additional reports of pediatric patients with invasive T asahii infection and an underlying malignant or nonmalignant hematologic disorder. Results Of the 19 cases of invasive T asahii infection, the most commonly reported underlying hematologic disorder was acute lymphoblastic leukenia (47%), followed by acute myelogenous leukemia (21%). Most of the patients (94%) had neutropenia, defined as an absolute neutrophil count of

Antibodies to capsular polysaccharides and pilus proteins develop in recovering adults., Immunization of nonpregnant adults could help prevent invasive group B Streptococcus (GBS) infections, but adult immune responses have not been investigated. We defined capsular polysaccharide (CPS) and pilus island (PI) surface antigen distribution and expression and immune responses to GBS infection in nonpregnant adults. Prospective surveillance from 7 hospitals in Houston, Texas, USA, identified 102 adults with GBS bacteremia; 43% had skin/soft tissue infection, 16% bacteremia without focus, and 12% osteomyelitis. CPS-specific IgG was determined by ELISA and pilus-specific IgG by multiplex immunoassay. CPS types were Ia (24.5%), Ib (12.7%), II (9.8%), III (16.7%), IV (13.7%), and V (12.7%); 9.8% were nontypeable by serologic methods. Pili, expressed by 89%, were most often PI-2a. CPS and pilus-specific IgG increased during convalescence among patients with strains expressing CPS or PI. All GBS expressed CPS or PI; 79% expressed both. Increased antibodies to CPS and PI during recovery suggests that GBS bacteremia in adults is potentially vaccine preventable.

Globally, group BStreptococcus(GBS) remains the leading cause of sepsis and meningitis in young infants, with its greatest burden in the first 90 days of life. Intrapartum antibiotic prophylaxis (IAP) for women at risk of transmitting GBS to their newborns has been effective in reducing, but not eliminating, the young infant GBS disease burden in many high income countries. However, identification of women at risk and administration of IAP is very difficult in many low and middle income country (LMIC) settings, and is not possible for home deliveries. Immunization of pregnant women with a GBS vaccine represents an alternate pathway to protecting newborns from GBS disease, through the transplacental antibody transfer to the fetus in utero. This approach to prevent GBS disease in young infants is currently under development, and is approaching late stage clinical evaluation.This manuscript includes a review of the natural history of the disease, global disease burden estimates, diagnosis and existing control options in different settings, the biological rationale for a vaccine including previous supportive studies, analysis of current candidates in development, possible correlates of protection and current status of immunogenicity assays. Future potential vaccine development pathways to licensure and use in LMICs, trial design and implementation options are discussed, with the objective to provide a basis for reflection, rather than recommendations.

Streptococcus agalactiae (Group B Streptococcus, GBS) causes life-threatening infections in newborns and adults with chronic medical conditions. Serotype IV strains are emerging both among carriers and as cause of invasive disease and recent studies revealed two main Sequence Types (STs), ST-452 and ST-459 assigned to Clonal Complexes CC23 and CC1, respectively. Whole genome sequencing of 70 type IV GBS and subsequent phylogenetic analysis elucidated the localization of type IV isolates in a SNP-based phylogenetic tree and suggested that ST-452 could have originated through genetic recombination. SNPs density analysis of the core genome confirmed that the founder strain of this lineage originated from a single large horizontal gene transfer event between CC23 and the hypervirulent CC17. Indeed, ST-452 genomes are composed by two parts that are nearly identical to corresponding regions in ST-24 (CC23) and ST-291 (CC17). Chromosome mapping of the major GBS virulence factors showed that ST-452 strains have an intermediate yet unique profile among CC23 and CC17 strains. We described unreported large recombination events, involving the cps IV operon and resulting in the expansion of serotype IV to CC23. This work sheds further light on the evolution of GBS providing new insights on the recent emergence of serotype IV.

Background Group A rotaviruses (RVA) are a significant cause of pediatric gastroenteritis worldwide. The New Vaccine Surveillance Network (NVSN) has conducted active surveillance for RVA at pediatric hospitals and emergency departments at 3-7 geographically diverse sites in the United States since 2006. Methods Over 6 consecutive years, from 2008 to 2013, 1523 samples from NVSN sites that were tested positive by a Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention for genotyping. Results In the 2009, 2010, and 2011 seasons, genotype G3P[8] was the predominant genotype throughout the network, with a 46%-84% prevalence. In the 2012 season, G12P[8] replaced G3P[8] as the most common genotype, with a 70% prevalence, and this trend persisted in 2013 (68.0% prevalence). Vaccine (RotaTeq; Rotarix) strains were detected in 0.6%-3.4% of genotyped samples each season. Uncommon and unusual strains (eg, G8P[4], G3P[24], G2P[8], G3P[4], G3P[6], G24P[14], G4P[6], and G9P[4]) were detected sporadically over the study period. Year, study site, and race were found to be significant predictors of genotype. Conclusions Continued active surveillance is needed to monitor RVA genotypes in the United States and to detect potential changes since vaccine licensure.

BACKGROUND Pertussis booster vaccine (Tdap) recommendations assume that pertussis-specific antibodies in women immunized preconception, during, or after previous pregnancies persist at sufficient levels to protect newborn infants. METHODS Pertussis-specific immunoglobulin G (IgG) was measured by IgG-specific enzyme-linked immunosorbent assay (ELISA) in maternal-umbilical cord serum pairs where mothers received Tdap during the prior 2 years. Geometric mean concentrations (GMCs) of pertussis antibodies and cord-maternal GMC ratios were calculated. RESULTS One hundred five mothers (mean age, 25.3 years [range, 15.3-38.4 years]; mean gestation, 39 weeks [range, 37-43 weeks]) immunized with Tdap vaccine a mean of 13.7 months (range, 2.3-23.9 months) previously were included; 72 (69%) had received Tdap postpartum, 31 at a routine healthcare visit and 2 as contacts of another newborn. There was no difference in GMCs for pertussis-specific IgG in maternal delivery or infant cord sera for women immunized before (n = 86) or during (n = 19) early pregnancy. Placental transport of antibodies was 121%-186% from mothers immunized before and during pregnancy, respectively. Estimated GMC of IgG to pertussis toxin was

OBJECTIVE:Group B Streptococcus (GBS) is the leading cause of meningitis in young infants. We evaluated long-term outcomes among GBS meningitis survivors. We hypothesized that despite reduced mortality, GBS meningitis would remain a significant cause of morbidity among GBS survivors.METHODS:Ninety term and near-term infants diagnosed with GBS meningitis from 1998 through 2006 were identified from 2 children’s hospitals. Five died acutely, and 5 died at 6 months to 3 years of age. Forty-three survivors (54%; mean age 6.8, range 3–12 years) were consented for evaluation and underwent physical and neurologic examinations, hearing and vision screening, and standardized developmental assessments. Associations among presenting features, laboratory parameters, neurologic status at hospital discharge, and later developmental outcomes were explored by using descriptive statistics and logistic regression.RESULTS:Twenty-four of 43 (56%) children evaluated demonstrated age-appropriate development, 11 (25%) had mild-to-moderate impairment, and 8 (19%) had severe impairment. Admission features associated with death after hospital discharge or severe impairment included lethargy (P = .003), respiratory distress (P = .022), coma or semicoma (P = .022), seizures (P = .015), bulging fontanel (P = .034), leukopenia (P = .026), acidosis (P = .024), cerebrospinal fluid protein >300 mg/dL (P = .006), cerebrospinal fluid glucose CONCLUSIONS:Survivors of GBS meningitis continue to have substantial long-term morbidity, highlighting the need for ongoing developmental follow-up and prevention strategies such as maternal immunization.

To characterize true coagulase-negative Staphylococcus (CoNS) infections in infants receiving neonatal intensive care.Retrospective cohort study of neonatal intensive care unit (NICU) infants with clinical sepsis and CoNS isolated from ≥ 2 blood cultures (BCs) or one BC and a sterile site (proved infection) or CoNS isolated from one BC and deemed significant after blinded data review (probable infection).In all, 98% of 40 proved and 96% of 55 probable infections occurred in infants with birth weight (BW)2000 g and gestation34 weeks. Total central lines (CLs) placed, but not CL duration or presence in situ, predicted proved (odds ratio (OR) 3.5, 95% confidence interval (CI) 1.4 to 8.3; P=0.005) and probable infection (OR 2.7, 95% CI 1.3 to 5.6; P=0.007) by multivariate analysis as did lethargy and gastric residuals.True CoNS infection is unlikely in infants with BW2000 g and gestation34 weeks. Total CL required for care, lethargy and gastric residuals predicted true CoNS infection.

Background Mothers often are the source of pertussis illness in young infants. The Centers for Disease Control and Prevention recommend tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine for postpartum women before hospital discharge. In January 2008, this recommendation was implemented in a predominantly Hispanic, medically underserved population at Ben Taub General Hospital (BTGH) in Houston (hereafter the intervention population). Methods A cross-sectional study compared preintervention (July 2000 through December 2007) and postintervention (January 2008 through May 2009) periods. Pertussis diagnosis was determined using International Classification of Diseases, Ninth Revision (ICD-9) codes and microbiology reports from 4 major children's hospitals in Houston. Only those infants ≤6 months of age with laboratory-confirmed pertussis illness were included. The proportions of pertussis-infected infants born at BTGH in the pre- and postintervention periods were compared. Results Of 514 infants with pertussis, 378 (73.5%) were identified during preintervention and 136 (26.5%) during postintervention years. These groups were similar in age (mean, 79.3 vs 72 days; P = .08), sex (males, 55% vs 52%; P = .48), length of hospitalization (mean, 9.7 vs 10.7 days; P = .62), mortality (2 deaths each; P = .29) and hospital of pertussis diagnosis. After adjustment for age, sex, and ethnicity, the proportions of pertussis-infected infants born at BTGH and potentially protected through maternal postpartum Tdap immunization were similar for the 2 periods (6.9% vs 8.8%; odds ratio, 1.06; 95% confidence interval, 0.5-2.2; P = .87). Conclusions Immunizing only postpartum mothers with Tdap vaccine did not reduce pertussis illness in infants ≤6 months of age. Efforts should be directed at immunizing all household and key contacts of newborns with Tdap, not just mothers.

We report an outbreak ofBacillusbacteremia among premature infants during a construction project. Our investigation revealed potential environmental sources. After replacement of air filters, cleaning of the unit, emphasis on hand hygiene, and relocation of the loading dock for linen and supply delivery, no further cases were detected.