Group B Streptococcus Meningitis Research Articles

Group B Streptococcus meningitis following subarachnoid hemorrhage suspicions: a case report

BackgroundBacterial meningitis is a life-threatening disease associated with high morbidity and mortality. Subarachnoid hemorrhage (SAH) can accompany bacterial meningitis in adult patients in <1% of cases and significantly worsens the patient’s prognosis.Case reportA 58-year-old man presented to the emergency department complaining of a 5-day history of progressive abdominal pain, when he suddenly developed “the worst headache of his life” and suffered a 4-minute seizure. Computed tomography head showed SAH. An emergent cerebral angiogram was negative for any bleeding source, and attention shifted to meningoencephalitis. Ultimately, the patient was found to have Group B Streptococcus (GBS) meningitis on cerebrospinal fluid polymerase chain reaction.ConclusionTo the best of our knowledge, this patient’s presentation of GBS meningitis, masked by a classic aneurysmal SAH presentation, represents a rare and acute presentation of an underlying disease complication. Increasing awareness of this presentation can support more rapid diagnosis, earlier treatment, and improved outcomes for affected patients.

Stillbirths and Neonatal Deaths Caused by Group B Streptococcus in Africa and South Asia Identified Through Child Health and Mortality Prevention Surveillance (CHAMPS).

Invasive Group B Streptococcus (GBS) is a common cause of early-onset neonatal sepsis and is also associated with stillbirth. This study aimed to determine the proportion of stillborn infants and infants who died between 0 and 90 days attributable to GBS using postmortem minimally invasive tissue sampling (MITS) in 7 low- and middle-income countries (LMICs) participating in Child Health and Mortality Prevention Surveillance (CHAMPS). Deaths that occurred between December 2016 and December 2021 were investigated with MITS, including culture for bacteria of blood and cerebrospinal fluid (CSF), multipathogen polymerase chain reaction on blood, CSF, and lung tissue and histopathology of lung, liver, and brain. Data collection included clinical record review and verbal autopsy. Expert panels reviewed all information and assigned causes of death. We evaluated 2966 deaths, including stillborn infants (n = 1322), infants who died during first day of life (0 to <24 hours, n = 597), early neonatal deaths (END) (1 day to <7 days; END; n = 593), and deaths from 7 to 90 days (n = 454). Group B Streptococcus was determined to be in the causal pathway of death for 2.7% of infants (79 of 2, 966; range, 0.3% in Sierra Leone to 7.2% in South Africa), including 2.3% (31 of 1322) of stillbirths, 4.7% (28 of 597) 0 to <24 hours, 1.9% (11 of 593) END, and 2.0% (9 of 454) of deaths from 7 to 90 days of age. Among deaths attributed to GBS with birth weight data available, 61.9% (39 of 63) of decedents weighed <2500 grams at birth. Group B Streptococcus sepsis was the postmortem diagnosis for 100% (31 of 31) of stillbirths. For deaths <90 days, postmortem diagnoses included GBS sepsis (83.3%, 40 of 48), GBS meningitis (4.2%, 2 of 48), and GBS pneumonia (2.1%, 1 of 48). Our study reveals significant heterogeneity in the contribution of invasive GBS disease to infant mortality across different countries, emphasizing the need for tailored prevention strategies. Moreover, our findings highlight the substantial impact of GBS on stillbirths, shedding light on a previously underestimated aspect in LMICs.

The Group B Streptococcal Adhesin BspC Interacts with Host Cytokeratin 19 To Promote Colonization of the Female Reproductive Tract.

ABSTRACTStreptococcus agalactiae, otherwise known as Group B Streptococcus (GBS), is an opportunistic pathogen that vaginally colonizes approximately one third of healthy women. During pregnancy, this can lead to in utero infection, resulting in premature rupture of membranes, chorioamnionitis, and stillbirths. Furthermore, GBS causes serious infection in newborns, including sepsis, pneumonia, and meningitis. Previous studies have indicated that GBS antigen (Ag) I/II family proteins promote interaction with vaginal epithelial cells; thus, we hypothesized that the Ag I/II Group B streptococcal surface protein C (BspC) contributes to GBS colonization of the female reproductive tract (FRT). Here, we show that a ΔbspC mutant has decreased bacterial adherence to vaginal, ecto-, and endocervical cells, as well as decreased auto-aggregation and biofilm-like formation on cell monolayers. Using a murine model of vaginal colonization, we observed that the ΔbspC mutant strain exhibited a significant fitness defect compared to wild-type (WT) GBS and was less able to ascend to the cervix and uterus in vivo, resulting in reduced neutrophil chemokine signaling. Furthermore, we determined that BspC interacts directly with the host intermediate filament protein cytokeratin 19 (K19). Surface localization of K19 was increased during GBS infection, and interaction was mediated by the BspC variable (V) domain. Finally, mice treated with a drug that targets the BspC V-domain exhibited reduced bacterial loads in the vaginal lumen and reproductive tissues. These results demonstrate the importance of BspC in promoting GBS colonization of the FRT and that it may be targeted therapeutically to reduce GBS vaginal persistence and ascending infection.

Comparison of Neurodevelopmental Outcomes in Children With Group B Streptococcal Sepsis and Meningitis.

To theEditor—We read with interest the Clinical Infectious Diseases supplement by Professor Lawn et al [1] describing findings from a series of studies assessing neurodevelopmental outcomes following invasive group B streptococcal (GBS) disease in infancy. These important studies from South Africa, Mozambique, India, The Netherlands, and Denmark begin to fill an important evidence gap regarding the long-term outcomes of GBS sepsis and meningitis in infancy, including data from low- and middle-income countries [1]. We have previously shown that GBS is the leading cause of sepsis and meningitis in infants <3 months of age in the United Kingdom (UK) [2], yet the burden of neurodevelopmental sequelae following GBS disease, particularly sepsis, is largely unquantified. Thus, we undertook an observational study to describe the neurodevelopmental outcomes of survivors of young infant (<3 months of age) GBS sepsis or of bacterial meningitis (any pathogen) in the UK. Participants were recruited via 2 sources: (1) Parents/carers of children who participated in a meningitis surveillance study conducted in 2010–2013 (n = 661) were contacted and invited to participate [3]; (2) infants <90 days of age with GBS cultured from a normally sterile site born between January 2011 and May 2014 were identified from the UK Health Security Agency national surveillance database used by laboratories to report clinically significant infections electronically [4].

Streptococcus agalactiae meningitis presenting with cerebral infarction in an adult patient: Clinical case and review

Bacterial meningitis is an inflammation of the meninges associated with the invasion of bacteria. The etiologic agents vary by age group. Bacterial meningitis due to group B streptococcus (GBS) is common for the neonatal period but is deemed to be rare in adult patients. Since 2000, more than two-thirds of all cases occur in adults, which is becoming a growing problem worldwide. We present a rare case of GBS meningitis presented with cerebral infarction in an adult patient and briefly review the etiology and incidence of GBS infections in adults. There is an increasing incidence of cases in elderly patients, particularly in those with more medical comorbidities. Cerebral infarction as an adverse effect in bacterial meningitis is both a sign of severity and a predictor of a poor clinical outcome with a high mortality rate. Early recognition of the infection, a search for deep-seated infection, and early antimicrobial therapy are vital moments for successful management of the GBS disease.

Epidemiology and bacterial characteristics of invasive group B streptococcus disease: a population-based study in Japan in 2010-2020.

This is the first report on a population-based prospective study of invasive group B streptococcus (GBS) disease among children aged <15 years conducted over a period of 11 years in Japan. This study investigated the incidence and clinical manifestations of invasive GBS disease in children in Chiba Prefecture, Japan, and analysed the serotypes and drug susceptibility of GBS strains isolated during the study period. Overall, 127 episodes of invasive GBS disease were reported in 123 patients. Of these, 124 were observed in 120 patients aged <1 year, and the remaining three episodes were reported in a 9-year-old child and two 14-year-old children with underlying disease. For patients aged <1 year, the incidence rate per 1000 live births was 0.24 (0.15-0.36). The incidences of early-onset disease and late-onset disease were 0.04 (0.0-0.09) and 0.17 (0.08-0.25), respectively. The rate of meningitis was 45.2%, and the incidence of GBS meningitis was higher than that of other invasive diseases among children in Japan. Of the 109 patients for whom prognosis was available, 7 (6.4%) died and 21 (19.3%) had sequelae. In total, 68 strains were analysed. The most common were serotype III strains (n = 42, 61.8%), especially serotype III/ST17 strains (n = 22, 32.4%). This study showed that the incidence of invasive GBS disease among Japanese children was constant during the study period. Because of the high incidence of meningitis and disease burden, new preventive strategies, such as GBS vaccine, are essential.

Epidemiology and Trends of Infective Meningitis in Neonates and Infants Less than 3 Months Old in Hong Kong

ObjectivesMeningitis in neonates and young infants leads to significant morbidity and mortality worldwide. This study aimed to investigate pathogens, antibiotic resistance and secular change of incidence in Hong Kong. MethodsA retrospective search was performed on meningitis in neonates and infants aged <3 months in three Hong Kong public hospitals from 2004 to 2019. Medical charts were reviewed, with focus on the identification and antibiotic resistance of the pathogens. ResultsA total of 200 cases of meningitis were identified (67% were bacterial). Group B Streptococcus (GBS) and Escherichia coli (E. coli) were the commonest bacterial pathogens. The annual rates of early-onset GBS meningitis decreased after the implementation of universal GBS screening and intrapartum antibiotic prophylaxis (IAP) in 2012, while that of late-onset GBS meningitis remained similar. A significant portion of E. coli isolates were resistant to ampicillin and/or gentamicin. ConclusionGBS and E. coli were the most common bacteria for meningitis in this age group. The annual rate of bacterial meningitis in Hong Kong has declined in recent years, which has been attributed to the decline in early-onset GBS meningitis due to universal GBS screening and IAP. Antimicrobial-resistant bacterial strains that cause meningitis require further clinical and public health attention.

Neonatal susceptibility to meningitis results from the immaturity of epithelial barriers and gut microbiota.

Neonates are highly susceptible to bacterial meningitis as compared to children and adults. Group B streptococcus (GBS) is a major cause of neonatal meningitis. Neonatal meningitis can result from GBS intestinal colonization and translocation across the intestinal barrier (IB). Here, we show that the immaturity of the neonatal intestinal microbiota leads to low resistance to GBS intestinal colonization and permissiveness of the gut-vascular barrier. Moreover, the age-dependent but microbiota-independent Wnt activity in intestinal and choroid plexus (CP) epithelia results in a lower degree of cell-cell junctions' polarization, which favors bacterial translocation. This study thus reveals that neonatal susceptibility to GBS meningitis results from the age-dependent immaturity of the intestinal microbiota and developmental pathways associated with neonatal tissue growth, which both concur to GBS gut colonization, systemic dissemination, and neuroinvasion. Whereas the activation of developmental pathways is intrinsic to neonates, interventions aimed at maturing the microbiota may help prevent neonatal meningitis.

Therapeutic development of group B Streptococcus meningitis by targeting a host cell signaling network involving EGFR

Group B Streptococcus (GBS) remains the most common Gram‐positive bacterium causing neonatal meningitis and GBS meningitis continues to be an important cause of mortality and morbidity. In this study, we showed that GBS penetration into the brain occurred initially in the meningeal and cortex capillaries, and exploits a defined host cell signaling network comprised of S1P2, EGFR, and CysLT1. GBS exploitation of such network in penetration of the blood–brain barrier was demonstrated by targeting S1P2, EGFR, and CysLT1 using pharmacological inhibition, gene knockout and knockdown cells, and gene knockout animals, as well as interrogation of the network (up‐ and downstream of each other). More importantly, counteracting such targets as a therapeutic adjunct to antibiotic therapy was beneficial in improving the outcome of animals with GBS meningitis. These findings indicate that investigating GBS penetration of the blood–brain barrier provides a novel approach for therapeutic development of GBS meningitis.

Identification of Zinc-Dependent Mechanisms Used by Group B Streptococcus To Overcome Calprotectin-Mediated Stress.

Nutritional immunity is an elegant host mechanism used to starve invading pathogens of necessary nutrient metals. Calprotectin, a metal-binding protein, is produced abundantly by neutrophils and is found in high concentrations within inflammatory sites during infection. Group B Streptococcus (GBS) colonizes the gastrointestinal and female reproductive tracts and is commonly associated with severe invasive infections in newborns such as pneumonia, sepsis, and meningitis. Although GBS infections induce robust neutrophil recruitment and inflammation, the dynamics of GBS and calprotectin interactions remain unknown. Here, we demonstrate that disease and colonizing isolate strains exhibit susceptibility to metal starvation by calprotectin. We constructed a mariner transposon (Krmit) mutant library in GBS and identified 258 genes that contribute to surviving calprotectin stress. Nearly 20% of all underrepresented mutants following treatment with calprotectin are predicted metal transporters, including known zinc systems. As calprotectin binds zinc with picomolar affinity, we investigated the contribution of GBS zinc uptake to overcoming calprotectin-imposed starvation. Quantitative reverse transcriptase PCR (qRT-PCR) revealed a significant upregulation of genes encoding zinc-binding proteins, adcA, adcAII, and lmb, following calprotectin exposure, while growth in calprotectin revealed a significant defect for a global zinc acquisition mutant (ΔadcAΔadcAIIΔlmb) compared to growth of the GBS wild-type (WT) strain. Furthermore, mice challenged with the ΔadcAΔadcAIIΔlmb mutant exhibited decreased mortality and significantly reduced bacterial burden in the brain compared to mice infected with WT GBS; this difference was abrogated in calprotectin knockout mice. Collectively, these data suggest that GBS zinc transport machinery is important for combatting zinc chelation by calprotectin and establishing invasive disease.IMPORTANCE Group B Streptococcus (GBS) asymptomatically colonizes the female reproductive tract but is a common causative agent of meningitis. GBS meningitis is characterized by extensive infiltration of neutrophils carrying high concentrations of calprotectin, a metal chelator. To persist within inflammatory sites and cause invasive disease, GBS must circumvent host starvation attempts. Here, we identified global requirements for GBS survival during calprotectin challenge, including known and putative systems involved in metal ion transport. We characterized the role of zinc import in tolerating calprotectin stress in vitro and in a mouse model of infection. We observed that a global zinc uptake mutant was less virulent than the parental GBS strain and found calprotectin knockout mice to be equally susceptible to infection by wild-type (WT) and mutant strains. These findings suggest that calprotectin production at the site of infection results in a zinc-limited environment and reveals the importance of GBS metal homeostasis to invasive disease.

Ampicillin Dose for Early and Late-Onset Group B Streptococcal Disease in Neonates.

Ampicillin is frequently used in neonates for early- and late-onset group B streptococcal (GBS) disease. In 2019, the American Academy of Pediatrics (AAP) published guidelines for GBS which included updated dosing recommendations for ampicillin for bacteremia and provided specific dosing recommendations for meningitis. The dosing recommendations in the guidelines were based off the 2018 Report of the Committee on Infectious Diseases (i.e., Red Book), which differed from the 2015 Red Book. For bacteremia, no dosing changes were recommended for ampicillin dosing in neonates ≤ 7 days of postnatal age (PNA), but less frequent dosing intervals were recommended for neonates > 7 days PNA. For meningitis, increased dosing recommendations were provided in the update. However, the rationale and supporting evidence for these changes were not provided. A literature search was performed to review articles pertaining to the pharmacokinetics (PK), pharmacodynamics (PD) and safety of ampicillin in neonates. The ampicillin dosing recommendations in the AAP guidelines were mainly supported by a 2014 publication that evaluated the PK and PD of ampicillin in neonates with gestational age (GA) of 24 to 41 weeks and PNA of 0 to 25 days. The proposed dosing from this study for bacteremia is included in the 2018 Red Book and 2019 guidelines. For meningitis, no supporting evidence was identified for the dosing recommendations in the 2018 Red Book and 2019 guidelines. Only one study has evaluated ampicillin concentrations in cerebrospinal fluid, but proposed dosing from this study was much lower than that included in the guidelines. The high ampicillin doses for GBS meningitis should be used with caution, as high ampicillin concentrations have been associated with seizures and no studies have evaluated efficacy of this dosing strategy. The purpose of this review is to identify key pieces of literature regarding dosing recommendations and safety of ampicillin in neonates. KEY POINTS: · Recent guidelines provide dosing recommendations for ampicillin, but the supporting evidence is not included.. · Literature supporting evidence for ampicillin dosing for bacteremia is available, but not for dosing for meningitis.. · Recommended meningitis dose may result in supratherapeutic concentrations and increase seizure risk..

&lt;p&gt;Group B Streptococcal Meningitis in a Healthy Young Woman: A Case Report&lt;/p&gt;

Group B streptococcus (GBS) is a rare cause of meningitis in adults that commonly affects patients with multiple underlying comorbidities. Although it is uncommon, it typically progresses very rapidly and has a high mortality rate as compared to other causes of bacterial meningitis. Here, we report a patient with GBS meningitis who had no underlying medical illness and presented with multiple episodes of seizure within hours of developing fever. Cerebrospinal fluid analysis results were consistent with bacterial meningitis, and blood cultures grew GBS. She was treated with intravenous ceftriaxone for 2 weeks and made a great recovery without any sequalae. In conclusion, although GBS meningitis is uncommon in adults, it is a serious medical disease and associated with a high mortality rate. To the best of our knowledge, this patient represents one of the few reported cases of GBS meningitis in a previously healthy young adult.

Multidimensional Proteome Profiling of Blood-Brain Barrier Perturbation by Group B Streptococcus.

Group B Streptococcus (GBS) remains the leading cause of neonatal meningitis, a disease associated with high rates of adverse neurological sequelae. The in vivo relationship between GBS and brain tissues remains poorly characterized, partly because past studies had focused on microbial rather than host processes. Additionally, the field has not capitalized on systems-level technologies to probe the host-pathogen relationship. Here, we use multiplexed quantitative proteomics to investigate the effect of GBS infection in the murine brain at various levels of tissue complexity, beginning with the whole organ and moving to brain vascular substructures. Infected whole brains showed classical signatures associated with the acute-phase response. In isolated brain microvessels, classical blood-brain barrier proteins were unaltered, but interferon signaling and leukocyte recruitment proteins were upregulated. The choroid plexus showed increases in peripheral immune cell proteins. Proteins that increased in abundance in the vasculature during GBS invasion were associated with major histocompatibility complex (MHC) class I antigen processing and endoplasmic reticulum dysfunction, a finding which correlated with altered host protein glycosylation profiles. Globally, there was low concordance between the infection proteome of whole brains and isolated vascular tissues. This report underscores the utility of unbiased, systems-scale analyses of functional tissue substructures for understanding disease.IMPORTANCE Group B Streptococcus (GBS) meningitis remains a major cause of poor health outcomes very early in life. Both the host-pathogen relationship leading to disease and the massive host response to infection contributing to these poor outcomes are orchestrated at the tissue and cell type levels. GBS meningitis is thought to result when bacteria present in the blood circumvent the selectively permeable vascular barriers that feed the brain. Additionally, tissue damage subsequent to bacterial invasion is mediated by inflammation and by immune cells from the periphery crossing the blood-brain barrier. Indeed, the vasculature plays a central role in disease processes occurring during GBS infection of the brain. Here, we employed quantitative proteomic analysis of brain vascular substructures during invasive GBS disease. We used the generated data to map molecular alterations associated with tissue perturbation, finding widespread intracellular dysfunction and punctuating the importance of investigations relegated to tissue type over the whole organ.

Neurodevelopmental Impairment at 1 Year of Age in Infants With Previous Invasive Group B Streptococcal Sepsis and Meningitis.

Invasive group B streptococcal (GBS) disease causes considerable morbidity and mortality in young infants, and 18% of GBS-meningitis survivors have moderate-to-severe neurodevelopmental impairment. However, there is a paucity of data regarding neurologic impairment following GBS sepsis. A case-control study was undertaken in infants at 3 secondary-tertiary hospitals in Johannesburg, South Africa. Neurodevelopmental assessments were done at 1 year of age using the Denver II Developmental screening tool. A case was defined as isolation of GBS from blood or cerebrospinal fluid in infants less than 90 days of age. Three healthy controls (range: 1-6) were matched to maternal age, maternal HIV-infection status, gestational age and timing of enrollment. Of 122 invasive GBS cases, 78 (63.9%) had sepsis and 44 (36.1%) meningitis. Twenty-two (18%) invasive GBS cases (17 of 78; 21.8% with sepsis and 5 of 44; 11.4% with meningitis) died during the course of hospitalization, and a further 2 (1.6%; 1 sepsis and 1 meningitis case) died by 1 year of age. Five (1.1%) of 449 controls died by 1 year of age. Of the 45 GBS sepsis cases and 141 matched controls followed through to 1 year of age, 11 (24.4%) cases (3 with moderate-to-severe impairment) and 10 (7.1%) controls had an abnormal Denver score with an adjusted (for gender) odds ratio of 3.51; 95% confidence interval (CI): 1.23-10.04; P = 0.019. Four (20%) of the 20 GBS meningitis cases compared with 1 (1.5%) control had neurologic impairment at 1-year of age (aOR: 8.29; 95% CI: 0.88-78.3; P = 0.065) CONCLUSION:: In this setting, invasive GBS disease is associated with a high mortality. Infant survivors of invasive GBS sepsis compared with controls had 3.5-fold greater odds of neurologic impairment by 1 year of age. This corroborates the need for strategies to prevent invasive GBS disease.

Neonatal Susceptibility to Meningitis Results from the Immaturity of Epithelial Barriers and Gut Microbiota

Neonates are highly susceptible to bacterial meningitis as compared to children and adults. Group B streptococcus (GBS) is a major cause of neonatal meningitis. Neonatal meningitis can result from GBS intestinal colonization and translocation across the intestinal barrier (IB). Here, we show that the immaturity of the neonatal intestinal microbiota results in low resistance to GBS intestinal colonization and higher permissiveness of the gut vascular barrier. Additionally, the age-dependent but microbiota-independent Wnt activity in intestinal and choroid plexus (CP) epithelia results in a lower degree of cell-cell junctions’ polarization which favors bacterial translocation. This study reveals that neonatal susceptibility to GBS meningitis results from the age-dependent immaturity of the microbiota and developmental pathways associated with neonatal tissue growth, which concur to GBS gut colonization, systemic dissemination and neuroinvasion. Whereas the activation of developmental pathways is intrinsic to neonates, interventions aimed at maturing the microbiota may help prevent neonatal meningitis.

Perinatal hormones favor CC17 group B Streptococcus intestinal translocation through M cells and hypervirulence in neonates.

Group B Streptococcus (GBS) is the leading cause of invasive bacterial neonatal infections. Late-onset diseases (LOD) occur between 7 and 89 days of life and are largely due to the CC17 GBS hypervirulent clone. We studied the impact of estradiol (E2) and progesterone (P4), which impregnate the fetus during pregnancy, on GBS neonatal infection in cellular and mouse models of hormonal exposure corresponding to concentrations found at birth (E2-P4 C0) and over 7 days old (E2-P4 C7). Using representative GBS isolates, we show that E2-P4 C7 concentrations specifically favor CC17 GBS meningitis following mice oral infection. CC17 GBS crosses the intestinal barrier through M cells. This process mediated by the CC17-specific surface protein Srr2 is enhanced by E2-P4 C7 concentrations which promote M cell differentiation and CC17 GBS invasiveness. Our findings provide an explanation for CC17 GBS responsibility in LOD in link with neonatal gastrointestinal tract maturation and hormonal imprint.

Clinical analysis of children with group B streptococcal meningitis in 2013-2017 in a single center

Objective: To explore the clinical features, the risk factors of mortality and drug resistance of the isolates in patients with group B streptococcus (GBS) meningitis. Methods: A retrospective analysis was performed in 96 children with GBS meningitis (46 males and 50 females) at Beijing Children's Hospital Affiliated to Capital Medical University from January 2013 to October 2017. The clinical characteristics, prognosis and drug resistance were reviewed and analyzed. According to the onset time, the patients were divided into early onset disease (EOD, 0-6 days), late onset disease (LOD, 7-89 days) and very late onset disease (VLOD, 90 days-16 years), the clinical features were compared. According to the results of cranial imaging examination, the patients were divided into two groups: those with neurological complications and those without neurological complications. The influencing factors of neurological complications were analyzed. According to the outcome of 28 days after discharge, patients were divided into death group and survival group. The risk factors of mortality were analyzed by multivariate Logistic regression analysis. Non-numeric variables were analyzed with χ(2) test or Fisher's exact test. Numeric variable between groups were compared with nonparametric test. Results: A total of 96 patients were enrolled, including 18 (19%) EOD, 71 (74%) LOD and 7 (7%) VLOD cases. The median age of EOD cases was 2 days, with a range from 0 to 6 days. The median age of LOD cases was 31 days, with a range from 7 to 81 days. The median age of VLOD cases was 153 days, with a range from 95 to 214 days. Before the onset of the disease, the mother had mastitis in 6 cases and premature rupture of membranes in 6 cases. The common clinical manifestations of patients were fever (95%, 91/96), anorexia (65%, 62/96), seizure (56%, 54/96), and consciousness changes (36%, 35/96). The differences were statistically significant in gender (13/18 vs. 28/71 vs. 5/7, χ(2)=7.705, P=0.024), the number of cases who was admitted to intensive care unit (ICU) (5/18 vs. 31/71 vs. 0, χ(2)=6.065, P=0.042) and peripheral blood leukocyte (12(4, 18)×10(9)/L vs. 6(3, 11)×10(9)/L vs. 13(6, 17)×10(9)/L, H=9.885, P=0.007) in EOD group, LOD group and VLOD group. Cranial imaging was performed in 94 patients, 60 patients (64%) developed neurological complications, including subdural effusion (31/94, 33%), followed by intracranial hemorrhage (26/94, 28%), cerebral softening (19/94, 20%), cerebral atrophy (15/94, 16%), ependinitis (8/94, 9%) and hydrocephalus (4/94, 4%). By univariate χ(2) test analysis, seizure (63% (38/60) vs.41% (14/34), χ(2)=4.310, P=0.038) was a risk factor of neurological complications. Within 28 days after discharge, 88 patients survived and 8 patients died, with a fatality rate of 8%. The independent risk factors for the death were septic shock (OR: 9.548, 95% CI 1.439-63.356, P=0.019) and respiratory failure (OR: 7.053, 95% CI 1.160-42.888, P=0.034). All of isolates were susceptible to penicillin (68/68), ceftriaxone (47/47), cefepime (50/50), vancomycin (60/60) and linezolid (54/54), while the rates of resistance to tetracycline, levofloxacin, clindamycin and erythromycin were 5/12, 17/45, 38/46 and 32/37, respectively. Conclusions: The main type of GBS meningitis is late onset cases. The incidence of neurological complications was high. The independent risk factors for death were septic shock and respiratory failure. The strains were severely resistant to clindamycin and erythromycin.

Disease burden of neonatal invasive Group B Streptococcus infection in the Netherlands.

BackgroundGroup B Streptococcus (GBS) is the leading cause of neonatal sepsis and meningitis worldwide. We aimed to estimate the current burden of neonatal invasive GBS disease in the Netherlands, as a first step in providing an evidence base for policy makers on the potential benefits of a future maternal GBS vaccine.MethodsSurveillance of neonatal invasive GBS occurs at the National Reference Laboratory for Bacterial Meningitis, where culture isolates from cerebrospinal fluid and blood are sent by diagnostic laboratories. From the number of cultures we estimated the incidence of neonatal (age 0–90 days) GBS meningitis and sepsis. We constructed a disease progression model informed by literature and expert consultation to estimate the disease burden of neonatal invasive GBS infection. As many neonates with a probable GBS sepsis are never confirmed by blood culture, we further estimated the disease burden of unconfirmed cases of probable GBS sepsis in sensitivity analyses.ResultsAn estimated 97 cases and 6.5 deaths occurred in the Netherlands in 2017 due to culture positive neonatal invasive GBS infection. This incidence comprised 15 cases of meningitis and 42 cases of sepsis per 100.000 births, with an estimated mortality of 3.8 per 100.000 live births. A disease burden of 780 disability-adjusted life years (DALY) (95% CI 650–910) or 460 DALY per 100.000 live births was attributed to neonatal invasive GBS infection. In the sensitivity analysis including probable neonatal GBS sepsis the disease burden increased to 71 cases and 550 DALY (95% CI 460–650) per 100.000 live births.ConclusionIn conclusion, neonatal invasive GBS infection currently causes a substantial disease burden in the Netherlands. However, important evidence gaps are yet to be filled. Furthermore, cases of GBS sepsis lacking a positive blood culture may contribute considerably to this burden potentially preventable by a future GBS vaccine.

Etiology and Clinical Features of Full-Term Neonatal Bacterial Meningitis: A Multicenter Retrospective Cohort Study.

Objective: Neonatal bacterial meningitis is a severe infectious disease with a high risk of neurodevelopmental sequelae. The causative pathogens may be related to specific clinical features of the disease. Therefore, this study aimed at determining the pathogen-specific and clinical features of bacterial meningitis in full-term neonates.Methods: We enrolled neonates from the Shanghai Neonate Meningitis Cohort (2005–2017), which is a multicenter retrospective cohort that recruits almost all full-term neonates in Shanghai who underwent lumbar puncture. Patient history and clinical examination results were extracted from the computer-documented information systems of four hospitals. The trends of pathogen distribution were analyzed and differences in the clinical manifestations, treatment, and clinical outcomes at discharge were compared according to the causative pathogen. Logistic regression was used to evaluate the pathogen-specific risk of neurological complications.Results: In total, 518 cases of neonatal meningitis, including 189 proven cases, were included. Group B Streptococcus (GBS) and Escherichia coli (E. coli) were the leading pathogens in proven cases of early-onset and late-onset neonatal meningitis, respectively. The proportion of early-onset and late-onset GBS and late-onset E. coli meningitis cases increased gradually. GBS meningitis had the highest risk of neurological complications, whereas the overall incidence of hydrocephalus and brain abscess in E. coli was higher than that in GBS.Conclusions: Rates of neonatal GBS and E. coli meningitis were high in 2005–2017 in Shanghai, and the risk of neurological complications was also high. Therefore, active prevention, rational use of antibiotics, and continuous monitoring of GBS and E. coli in neonates should be initiated in Shanghai.

Brain imaging can predict neurodevelopmental outcome of Group B streptococcal meningitis in neonates.

The association between cranial ultrasound (CUS) or magnetic resonance imaging (MRI) lesions and neonatal Group B streptococcal (GBS) meningitis outcome has not been studied in detail. This retrospective study assessed CUS, cranial MRI and neurodevelopmental outcome in 50 neonates with GBS meningitis admitted to three neonatal intensive care units in the Netherlands between 1992 and 2014. Death, cognitive outcome and motor outcome below -1 SD were considered as adverse outcomes. CUS was available in all and MRIs in 31 infants (62%) with 28 CUS (56%) and 27 MRIs (87%) being abnormal. MRI lesions were multifocal (n=10, 37%), bilateral (n=22; 82%) and extensive (n=11; 41%). A total of 10 died in the neonatal period. Median age at assessment was 24months. Among survivors, abnormal cognitive outcome and motor outcome were seen in 23 and 20 patients, respectively. Abnormal CUS [odds ratio (OR) 5.3, p=0.017], extensive bilateral deep grey lesions (OR 6.7, p=0.035) and white matter lesions (OR 14.0, p=0.039) correlated with abnormal motor outcome. Extensive bilateral deep grey matter lesions correlated with abnormal cognitive outcome (OR 8.1, p=0.029). Abnormal CUS and the most severely affected MRIs were associated with poor neurodevelopmental outcome in neonatal GBS meningitis.