High-risk Escherichia coli clones that cause neonatal meningitis and association with recrudescent infection.

Neonatal meningitis is a devastating disease associated with high mortality and neurological sequelae. Escherichia coli is the second most common cause of neonatal meningitis in full-term infants (herein NMEC) and the most common cause of meningitis in preterm neonates. Here, we investigated the genomic relatedness of a collection of 58 NMEC isolates spanning 1974-2020 and isolated from seven different geographic regions. We show NMEC are comprised of diverse sequence types (STs), with ST95 (34.5%) and ST1193 (15.5%) the most common. No single virulence gene profile was conserved in all isolates; however, genes encoding fimbrial adhesins, iron acquisition systems, the K1 capsule, and O antigen types O18, O75, and O2 were most prevalent. Antibiotic resistance genes occurred infrequently in our collection. We also monitored the infection dynamics in three patients that suffered recrudescent invasive infection caused by the original infecting isolate despite appropriate antibiotic treatment based on antibiogram profile and resistance genotype. These patients exhibited severe gut dysbiosis. In one patient, the causative NMEC isolate was also detected in the fecal flora at the time of the second infection episode and after treatment. Thus, although antibiotics are the standard of care for NMEC treatment, our data suggest that failure to eliminate the causative NMEC that resides intestinally can lead to the existence of a refractory reservoir that may seed recrudescent infection.

Coverage gaps in empiric antibiotic regimens used to treat serious bacterial infections in neonates and children in Southeast Asia and the Pacific.

Background: High levels of antimicrobial resistance (AMR) are propagating deaths due to neonatal and paediatric infections globally. This is of particular concern in Southeast Asia and the Pacific, where healthcare resources are constrained and access to newer agents to treat multidrug-resistant pathogens is limited. Methods: To assess the coverage provided by commonly prescribed empiric antibiotic regimens for children in low- and middle-income countries in Southeast Asia and the Pacific, we built a weighted incidence syndromic combination antibiogram (WISCA), parameterised using data obtained from a systematic review of published literature incorporating WHO-defined SEARO and WPRO regions in Ovid MEDLINE, EMBASE, Global Health and PubMed. Susceptibility data for bacterial pathogens were extracted to provide coverage estimates for pre-specified antibiotics (aminopenicillins, gentamicin, third-generation cephalosporins and carbapenems), reported at the regional level. Findings: 6648 bacterial isolates from 11 countries across 86 papers were included in the Bayesian WISCA model, which weighted bacterial incidence and antimicrobial susceptibility of relevant isolates. Coverage provided by aminopenicillins in neonatal sepsis/meningitis was 26% (80% credible interval: 16-49) whilst gentamicin coverage was 45% (29-62). Third-generation cephalosporin coverage was only 29% (16-49) in neonatal sepsis/meningitis, 51% (38-64) in paediatric sepsis and 65% (51-77) in paediatric meningitis. Carbapenems were estimated to provide the highest coverage: 81% (65-90) in neonatal sepsis/meningitis, 83% (72-90) in paediatric sepsis and 79% (62-91) in paediatric meningitis. Interpretation: These findings reveal alarmingly high rates of resistance to commonly prescribed empirical therapies for neonatal and paediatric sepsis and meningitis in the Asia-Pacific region. Funding: This research was funded in whole, or in part, by the Wellcome Trust [220211]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. PCMW is supported by a National Health and Medical Research Council (NHMRC) Investigator Grant. NHMRC had no involvement in the design or conduct of the research.

Cerebrospinal fluid inflammatory markers to differentiate between neonatal bacterial meningitis and sepsis: A prospective study of diagnostic accuracy.

OBJECTIVES: We evaluated the diagnostic accuracy of cerebrospinal fluid (CSF) inflammatory markers for diagnosing bacterial meningitis in neonates with sepsis and/or meningitis. METHODS: Cases were identified from a prospective multicenter study including patients aged 0-3 months with Group B Streptococcal (GBS) or Escherichia coli culture positive sepsis/meningitis. CSF CXCL10, MDC, IL-6, IL-8, IL-10, TNF- α, MIF, IL-1RA, CXCL13, IL-1ß, CRP and procalcitonin concentrations were measured with Luminex technology. RESULTS: In 61/373 patients (17%) residual CSF from the lumbar puncture was available, of whom 16 (26%) had definitive meningitis, 15 (25%) probable meningitis and 30 (49%) had sepsis. All biomarkers were detectable in CSF and showed significantly higher concentrations in definitive meningitis versus sepsis patients and six biomarkers in probable meningitis versus sepsis patients. Discrimination between definitive meningitis and sepsis was excellent for IL-1RA (area under the receiver operating characteristic curve [AUC] 0.93), TNF-α (AUC 0.92), CXCL10 (AUC 0.90), IL-1ß (AUC 0.92), IL-6 (AUC 0.94), IL-10 (AUC 0.93) and a combination of IL-1RA, TNF-α, CXCL-10 and CSF leukocyte count (AUC 0.95). CSF leukocyte count remained the predictor with the highest diagnostic accuracy (AUC 0.96). CONCLUSION: CSF inflammatory markers can be used to differentiate between neonatal sepsis and meningitis.

Relevancia de los enterovirus en la meningitis neonatal / Relevance of enteroviruses in neonatal meningitis

Introducción: Las infecciones por enterovirus (EV) constituyen las infecciones más frecuentes en el periodo neonatal y provocan en muchos casos el ingreso hospitalario del recién nacido (RN). El objetivo del estudio es conocer la incidencia de los EV en la etiología de las meningitis neonatales y definir qué características clínicas presentan los RN con meningitis por EV. Material y método: Estudio observacional retrospectivo de cohortes. Incluye 91 RN con meningitis y edad gestacional mayor de 34 semanas (SG) atendidos en nuestro centro durante un periodo de 16 años. Resultados: El porcentaje de RN con meningitis por EV fue superior al de RN con meningitis bacteriana y representó el 78% (n=71). La mitad de los RN con infección por EV presentó antecedentes de ambiente epidémico entre sus cuidadores. La fiebre apareció en el 96% de los casos como signo clínico y, en general, las alteraciones del sensorio representaron las principales alteraciones neurológicas. Un 71,4% de los pacientes con infección por EV recibió antibióticos. La detección de EV en muestras de LCR mostró una elevada sensibilidad para el diagnóstico de meningitis por EV. Los tipos de EV más frecuentemente implicados fueron echovirus 11, coxsackievirus B5, echovirus 18, 25 y 7. Conclusiones: Los resultados de esta serie muestran que la infección por enterovirus es una causa común de meningitis neonatal. Estos datos subrayan la importancia de realizar pruebas de detección rápida de EV en lactantes con sospecha de meningitis. Ello permite obtener un diagnóstico precoz y reducir el tratamiento antibiótico, el tiempo de hospitalización y los costes relacionados.(AU)

Introduction: Enterovirus (EV) infections are the most frequent infections in the neonatal period and in many cases lead to hospital admission of the newborn (NB). The aim of this study was to determine the incidence of EV in the etiology of neonatal meningitis and to define the clinical characteristics of newborns with EV meningitis. Material and method: Retrospective observational cohort study. Including 91 NBs with meningitis and gestational age greater than 34 weeks gestational age (GA) attended in our center over a period of 16 years. Results: The percentage of NBs with EV meningitis was higher than that of NBs with bacterial meningitis (BM) and accounted for 78% (n=71). Half of the NBs with EV infection had a history of epidemic environment among their caregivers. Fever was present in 96% of cases as a clinical sign and, in general, sensory disturbances represented the main neurological alterations. Antibiotics (ATB) were given to 71.4% of patients with EV infection. Detection of EV in CSF samples showed a high sensitivity for the diagnosis of EV meningitis. The most frequently implicated EV types were echovirus 11, coxsackievirus B5, echovirus 18, 25 and 7. Conclusions: The results of this series show that enterovirus infection is a common cause of neonatal meningitis. These data underline the importance of rapid EV testing of infants with suspected meningitis. This allows early diagnosis and reduces antibiotic treatment, hospitalization time and related costs.(AU)

Relevance of enteroviruses in neonatal meningitis.

INTRODUCTION: Enterovirus (EV) infections are the most frequent infections in the neonatal period and in many cases lead to hospital admission of the newborn (NB). The aim of this study was to determine the incidence of EV in the etiology of neonatal meningitis and to define the clinical characteristics of newborns with EV meningitis. MATERIAL AND METHOD: Retrospective observational cohort study. Including 91 NBs with meningitis and gestational age greater than 34 weeks gestational age (GA) attended in our center over a period of 16 years. RESULTS: The percentage of NBs with EV meningitis was higher than that of NBs with bacterial meningitis (BM) and accounted for 78% (n=71). Half of the NBs with EV infection had a history of epidemic environment among their caregivers. Fever was present in 96% of cases as a clinical sign and, in general, sensory disturbances represented the main neurological alterations. Antibiotics (ATB) were given to 71.4% of patients with EV infection. Detection of EV in CSF samples showed a high sensitivity for the diagnosis of EV meningitis. The most frequently implicated EV types were echovirus 11, coxsackievirus B5, echovirus 18, 25 and 7. CONCLUSIONS: The results of this series show that enterovirus infection is a common cause of neonatal meningitis. These data underline the importance of rapid EV testing of infants with suspected meningitis. This allows early diagnosis and reduces antibiotic treatment, hospitalization time and related costs.

Waterhouse-Friderichsen Syndrome and Central Diabetes Insipidus Due to Escherichia coli Meningitis.

Waterhouse-Friderichsen syndrome and central diabetes insipidus are uncommon but potentially fatal endocrine and metabolic diseases. Waterhouse-Friderichsen syndrome is defined as adrenal insufficiency caused by adrenal hemorrhage, which is typically bilateral and most frequently due to meningococcal infection. It is usually diagnosed by necropsy. Central diabetes insipidus in children is often caused by trauma, intracranial lesions, autoimmune diseases, and infections. In addition, it can be caused by mutations in the AVP-NPII gene, although this occurs typically later in childhood rather than in the neonatal period. This report describes a term infant who developed Escherichia coli meningitis, which resulted in septic shock and disseminated intravascular coagulation. Abdominal ultrasound led to an early diagnosis of bilateral adrenal hemorrhage and appropriate treatment with corticosteroids. Symptomatic central diabetes insipidus developed a few days after the onset of meningitis. Intravenous vasopressin was effective in resolving hemodynamic instability. In conclusion, sepsis and meningitis may have severely affected the endocrine system in this patient. Early diagnosis and appropriate treatment for both diseases may have resulted in better clinical outcomes for this patient.

The Clinical and Genetic Characteristics of Streptococcus agalactiae Meningitis in Neonates.

Streptococcus agalactiae (Group B Streptococcus, GBS) is an important pathogen of bacterial meningitis in neonates. We aimed to investigate the clinical and genetic characteristics of neonatal GBS meningitis. All neonates with GBS meningitis at a tertiary level medical center in Taiwan between 2003 and 2020 were analyzed. Capsule serotyping, multilocus sequence typing, antimicrobial resistance, and whole-genome sequencing (WGS) were performed on the GBS isolates. We identified 48 neonates with GBS meningitis and 140 neonates with GBS sepsis. Neonates with GBS meningitis had significantly more severe clinical symptoms; thirty-seven neonates (77.8%) had neurological complications; seven (14.6%) neonates died; and 17 (41.5%) survivors had neurological sequelae at discharge. The most common serotypes that caused meningitis in neonates were type III (68.8%), Ia (20.8%), and Ib (8.3%). Sequence type (ST) is highly correlated with serotypes, and ST17/III GBS accounted for more than half of GBS meningitis cases (56.3%, n = 27), followed by ST19/Ia, ST23/Ia, and ST12/Ib. All GBS isolates were sensitive to ampicillin, but a high resistance rates of 72.3% and 70.7% to erythromycin and clindamycin, respectively, were noted in the cohort. The virulence and pilus genes varied greatly between different GBS serotypes. WGS analyses showed that the presence of PezT; BspC; and ICESag37 was likely associated with the occurrence of meningitis and was documented in 60.4%, 77.1%, and 52.1% of the GBS isolates that caused neonatal meningitis. We concluded that GBS meningitis can cause serious morbidity in neonates. Further experimental models are warranted to investigate the clinical and genetic relevance of GBS meningitis. Specific GBS strains that likely cause meningitis requires further investigation and clinical attention.

Microbial signatures of neonatal bacterial meningitis from multiple body sites.

As a common central nervous system infection in newborns, neonatal bacterial meningitis (NBM) can seriously affect their health and growth. However, although metagenomic approaches are being applied in clinical diagnostic practice, there are some limitations for whole metagenome sequencing and amplicon sequencing in handling low microbial biomass samples. Through a newly developed ultra-sensitive metagenomic sequencing method named 2bRAD-M, we investigated the microbial signatures of central nervous system infections in neonates admitted to the neonatal intensive care unit. Particularly, we recruited a total of 23 neonates suspected of having NBM and collected their blood, cerebrospinal fluid, and skin samples for 2bRAD-M sequencing. Then we developed a novel decontamination method (Reads Level Decontamination, RLD) for 2bRAD-M by which we efficiently denoised the sequencing data and found some potential biomarkers that have significantly different relative abundance between 12 patients that were diagnosed as NBM and 11 Non-NBM based on their cerebrospinal fluid (CSF) examination results. Specifically, we discovered 11 and 8 potential biomarkers for NBM in blood and CSF separately and further identified 16 and 35 microbial species that highly correlated with the physiological indicators in blood and CSF. Our study not only provide microbiological evidence to aid in the diagnosis of NBM but also demonstrated the application of an ultra-sensitive metagenomic sequencing method in pathogenesis study.

Case report: A rare multidrug-resistant Escherichia coli causes fatal neonatal meningoencephalitis.

Neonatal meningitis is rare but devastating disease. Multidrug-resistant (MDR, multi-drug resistant) bacteria are a major global health risk. We report an Escherichia coli meningitis isolate with multiple resistance patterns and unusual serotype (O75) that caused sudden neonatal death. The isolate was resistant to antibiotics other than cefoperazone/sulbactam and imipenem, challenging the combination of antibiotics commonly used in the empirical treatment of neonatal sepsis. Despite aggressive symptomatic and supportive treatment of the infant based on laboratory tests and clinical practice, the infant eventually died. This is the first case of meningoencephalitis due to serotype O75 reported in China. The presence of highly pathogenic multidrug-resistant microorganisms isolated in neonates underscores the need to implement rapid resistance diagnostic methods and should prompt consideration of alternatives to empiric treatment of neonatal bacterial meningitis.

Improved Diagnostics in Bacterial Neonatal Meningitis Using a Next-Generation Sequencing Platform.

INTRODUCTION: Bacterial meningitis in infants is an infrequent but life-threatening condition. Empiric therapy should begin as soon as meningitis is thought likely. Consequently, the causative microorganisms may not always be detected using culturing techniques, as cerebrospinal fluid (CSF) cultures are influenced by antibiotics. Nucleic acid amplification tests, such as polymerase chain reaction (PCR) (multiplex panels), may overcome this limitation but require a priori knowledge of the likely pathogen present within the sample. With this in mind, we investigated to what extent a culture-free, broad-range 16S rRNA gene next-generation sequencing (NGS) platform (MYcrobiota) could add to the microbiological diagnosis of meningitis. METHODS: Retrospective cohort study at level III neonatal intensive care unit. Included were all infants with suspected meningitis admitted between 10 November 2017 and 31 December 2020. A comparison was made of the bacterial pathogen detection rate between MYcrobiota and conventional bacterial culture. RESULTS: In a 3-year period, 37 CSF samples (diagnostic and follow-up) from 35 infants with proven or possible meningitis were available for MYcrobiota testing. MYcrobiota detected the presence of bacterial pathogens in 11 samples (30%), in contrast with the conventional CSF culture, which detected bacteria in 2 of 36 samples (5.6%). CONCLUSION: Addition of 16S rRNA sequencing to conventional culturing greatly improved the identification of the aetiology of bacterial meningitis compared to culturing of CSF samples alone.

Cost-effectiveness analysis of maternal vaccination against Group B streptococcus in Japan.

Background: Group B Streptococcus (GBS) is a leading pathogen causing life-threatening bacterial infections in neonates (early- or late-onset) and infants, and is associated with preterm and stillbirth. Japan introduced national guidelines to reduce early-onset neonatal GBS disease, with universal prenatal screening and intrapartum antimicrobial prophylaxis (IAP). However, screening/IAP does not prevent GBS associated late-onset disease, preterm or stillbirth. Maternal GBS vaccines in development are targeted at infant GBS disease but may provide benefit across perinatal outcomes. We aimed to assess cost-effectiveness of a future maternal GBS vaccine, for a base case prevention of infant GBS disease in combination with screening/IAP compared to screening/IAP alone. Methods: We used a decision tree model to estimate cases of infant GBS disease, deaths, and neuro-developmental impairment (NDI), GBS-related stillbirths, and the associated costs and loss in Quality-Adjusted Life Years (QALYs). We calculate the threshold price at which a vaccine would be cost-effective assuming a cost-effectiveness threshold of ¥5 million/QALY. We explored the potential benefit of a maternal GBS vaccine that also prevents preterm birth in a scenario analysis. Results: Maternal GBS vaccination in Japan could prevent an additional 142 infant GBS cases annually, including 5 deaths and 21 cases of NDI, and 13 stillbirths compared to screening/IAP alone. The incremental cost-effectiveness ratio (ICER) was ¥3.78 million/QALY with a vaccine cost of ¥5,000/dose. If the QALY lost for stillbirth is included, the ICER is reduced to ¥1.78 million/QALY. Median threshold vaccine price was ¥6,900 per dose (95 % uncertainty interval ¥5,100 to ¥9,200 per dose). If maternal GBS vaccination also prevented half of GBS-associated preterm, the ICER would be reduced to ¥1.88 million/QALY. Conclusions: An effective maternal GBS vaccine is likely to be considered cost-effective in Japan at a price of ¥5,000/dose. Effectiveness against other adverse perinatal outcomes would increase health benefits and cost-effectiveness.

A case of bacteremia and meningitis in a neonate infected with Group B Streptococcus via breastfeeding who survived without neurological sequelae: A case report.

Invasive neonatal infection with Group B Streptococcus (GBS) is a disease of concern that can lead to neurological sequelae. Guidelines for preventing mother-to-child transmission have been introduced to reduce the incidence of early-onset infection, but guidelines for controlling the late-onset form are lacking. Recently, the trans-breastfeeding route of transmission has been highlighted as an example of late-onset infection, but no consensus on how to manage such infections has been reached. In this report, we describe a case of late-onset bacteremia/meningitis in a neonate suspected to have been infected with GBS via breastfeeding. A vaginal culture test of the mother at 35 weeks' gestation was negative for GBS. Since she had symptoms of mastitis, breast milk and nipple cultures were also tested and found to be positive for the strain of GBS identified in the neonate on genetic analysis. Diagnosis of trans-mammary GBS infection is challenging because breastfeeding-related events are difficult to identify. In our case, the diagnosis was based on the mother's history of mastitis, and the patient was treated without escalation to sequelae. When a neonate develops a fever, physicians should consider GBS infection and examine the mother's medical history to facilitate accurate diagnosis, especially if the history includes mastitis. A breast milk culture should be performed if the mother has mastitis, especially in cases of infection in preterm infants and in recurrent cases.

Neonatal Meningitis-Causing Escherichia coli Induces Microglia Activation which Acts as a Double-Edged Sword in Bacterial Meningitis.

Bacterial meningitis is a devastating disease occurring worldwide, with up to half of survivors left with permanent neurological sequelae. Neonatal meningitis-causing Escherichia coli (NMEC) is the most common Gram-negative bacillary organism that causes meningitis, particularly during the neonatal period. Here, RNA-seq transcriptional profiles of microglia in response to NMEC infection show that microglia are activated to produce inflammatory factors. In addition, we found that the secretion of inflammatory factors is a double-edged sword that promotes polymorphonuclear neutrophil (PMN) recruitment to the brain to clear the pathogens but, at the same time, induces neuronal damage, which may be related to the neurological sequelae. New neuroprotective therapeutic strategies must be developed for the treatment of acute bacterial meningitis. We found that transforming growth factor-ß (TGF-ß) may be a strong candidate in the treatment of acute bacterial meningitis, as it shows a therapeutic effect on bacterial-meningitis-induced brain damage. Prevention of disease and early initiation of the appropriate treatment in patients with suspected or proven bacterial meningitis are the key factors in reducing morbidity and mortality. Novel antibiotic and adjuvant treatment strategies must be developed, and the main goal for new therapies will be dampening the inflammatory response. Based on this view, our findings may help develop novel strategies for bacterial meningitis treatment.

A high-throughput sequencing approach identifies immunotherapeutic targets for bacterial meningitis in neonates.

BACKGROUND: Worldwide, Escherichia coli is the leading cause of neonatal Gram-negative bacterial meningitis, but full understanding of the pathogenesis of this disease is not yet achieved. Moreover, to date, no vaccine is available against bacterial neonatal meningitis. METHODS: Here, we used Transposon Sequencing of saturated banks of mutants (TnSeq) to evaluate E. coli K1 genetic fitness in murine neonatal meningitis. We identified E. coli K1 genes encoding for factors important for systemic dissemination and brain infection, and focused on products with a likely outer-membrane or extra-cellular localization, as these are potential vaccine candidates. We used in vitro and in vivo models to study the efficacy of active and passive immunization. RESULTS: We selected for further study the conserved surface polysaccharide Poly-ß-(1-6)-N-Acetyl Glucosamine (PNAG), as a strong candidate for vaccine development. We found that PNAG was a virulence factor in our animal model. We showed that both passive and active immunization successfully prevented and/or treated meningitis caused by E. coli K1 in neonatal mice. We found an excellent opsonophagocytic killing activity of the antibodies to PNAG and in vitro these antibodies were also able to decrease binding, invasion and crossing of E. coli K1 through two blood brain barrier cell lines. Finally, to reinforce the potential of PNAG as a vaccine candidate in bacterial neonatal meningitis, we demonstrated that Group B Streptococcus, the main cause of neonatal meningitis in developed countries, also produced PNAG and that antibodies to PNAG could protect in vitro and in vivo against this major neonatal pathogen. INTERPRETATION: Altogether, these results indicate the utility of a high-throughput DNA sequencing method to identify potential immunotherapy targets for a pathogen, including in this study a potential broad-spectrum target for prevention of neonatal bacterial infections. FUNDINGS: ANR Seq-N-Vaq, Charles Hood Foundation, Hearst Foundation, and Groupe Pasteur Mutualité.

Ureaplasma-Driven Neonatal Neuroinflammation: Novel Insights from an Ovine Model.

Ureaplasma species (spp.) are considered commensals of the adult genitourinary tract, but have been associated with chorioamnionitis, preterm birth, and invasive infections in neonates, including meningitis. Data on mechanisms involved in Ureaplasma-driven neuroinflammation are scarce. The present study addressed brain inflammatory responses in preterm lambs exposed to Ureaplasma parvum (UP) in utero. 7 days after intra-amniotic injection of UP (n = 10) or saline (n = 11), lambs were surgically delivered at gestational day 128-129. Expression of inflammatory markers was assessed in different brain regions using qRT-PCR and in cerebrospinal fluid (CSF) by multiplex immunoassay. CSF was analyzed for UP presence using ureB-based real-time PCR, and MRI scans documented cerebral white matter area and cortical folding. Cerebral tissue levels of atypical chemokine receptor (ACKR) 3, caspases 1-like, 2, 7, and C-X-C chemokine receptor (CXCR) 4 mRNA, as well as CSF interleukin-8 protein concentrations were significantly increased in UP-exposed lambs. UP presence in CSF was confirmed in one animal. Cortical folding and white matter area did not differ among groups. The present study confirms a role of caspases and the transmembrane receptors ACKR3 and CXCR4 in Ureaplasma-driven neuroinflammation. Enhanced caspase 1-like, 2, and 7 expression may reflect cell death. Increased ACKR3 and CXCR4 expression has been associated with inflammatory central nervous system (CNS) diseases and impaired blood-brain barrier function. According to these data and previous in vitro findings from our group, we speculate that Ureaplasma-induced caspase and receptor responses affect CNS barrier properties and thus facilitate neuroinflammation.

Comparative genome analysis of Streptococcus strains to identify virulent genes causing neonatal meningitis.

AIM: To determine Streptococcus agalactiae genes responsible for causing neonatal meningitis. BACKGROUND: Streptococcus agalactiae strain 2603 V/R is causative agent of neonatal meningitis, maternal infection and sepsis in young children. World health organisation reported high burden of new born death caused by this bacterium. Streptococcus agalactiae colonizing epithelial cells of vagina and endothelial cells have high resistance to available antibiotic drugs which makes it essential to determine new drug targets. OBJECTIVES: To compare the genome of selected strain with the non-pathogenic strains of streptococcus and identify the virulent and antibiotic resistant genes for adaptation in host environment. METHOD: The whole genome of human pathogen Streptococcus agalactiae strain 2603 V/R was analysed and compared with Streptococcus dysgalactiae strains using visualization and annotation tools. Genomic islands, mobile genetic elements, virulent and resistant genes were studied. RESULTS: Genetically pathogenic strain is most similar to Streptococcus dysgalactiae subsp. equisimilis strain NCTC 7136. Comparative analysis revealed the importance of capsular polysaccharides and surface proteins responsible for avoiding immune system attachment to host epithelial cells and virulent behaviour. High number of genes coding for antibiotics resistance may provide a competitive advantage for survival of pathogenic Streptococcus agalactiae strain 2603 V/R in its niche. CONCLUSIONS: The comparative analysis of pathogenic strain Streptococcus agalactiae with non-pathogenic strains of Streptococcus dysgalactiae provided new insights in pathogenicity that could aid in recognization for new regions and genes for development of new drug development strategies considering presence of high number of resistance genes.

Progress of neonatal infection with Elizabethkingia anophelis / 国际儿科学杂志

Elizabethkingia anophelis is one of the most significant pathogens threatening human health.As an important opportunistic pathogen, it is prone to nosocomial infection outbreaks, and can cause neonatal meningitis, especially in prematurity, seriously affecting the safety and quality of life of children.E.anophelis has the characteristic of multi-drug resistance, which brings great challenges to clinical treatment.E.anophelis was commonly misidentified as E. meningosepticum in previous reports.In fact, E.anophelis accounts for a significant proportion of Elizabethkingia infections, which needs more attention.This article reviews the epidemiology of E. anophelis, clinical features of neonatal infection, drug sensitivity, treatment and prevention, in order to provide reference for clinical diagnosis and treatment.

A cross-sectional study of clinical features of bacterial meningitis among neonates presumed to have sepsis in a tertiary hospital, Dar es Salaam, Tanzania.

Identifying meningitis among neonates is usually challenging given the non-specific presentation and overlap with neonatal sepsis. This study was aimed at determining the pertinent clinical features that would suggest bacterial meningitis among infants with signs of possible serious bacterial infection and their outcomes. This hospital-based cross-sectional study was conducted among neonates presenting with clinical features of sepsis admitted at Muhimbili National Hospital (MNH) between May and December 2015. Detailed clinical features, blood cultures, and cerebrospinal fluid were obtained. The specimens were tested at the Central Pathology Laboratory at MNH. Short-term clinical outcome was also determined for recruited participants. One hundred and twenty-six neonates met the inclusion criteria and were recruited, males were 67 (53.2%) and the mean age of participants was 10.4 ± 7.9 days. Features of meningitis were noted among 19% (24/126) and very low birth weight neonates were observed to have a statistically higher prevalence of meningitis (p=0.038). Bacterial isolates from cerebrospinal fluid (CSF) culture were Klebsiella spp and E. coli, while predominant isolates from blood culture were Klebsiella spp (35%) and E. coli (20.6%). There was high resistance to ampicillin (91.2%), cloxacillin (94.1%), gentamycin (50%), and ceftriaxone (50%). A high mortality of 24.9% was noted. Neonatal meningitis is common among neonates with sepsis, and bacterial isolates were resistant to routinely used antibiotics. High mortality attributed to meningitis was noted at Muhimbili National Hospital.

Intrauterine and Perinatal Infections.

Imaging plays an important role in evaluating patients with suspected intrauterine and perinatal infections. Advances in fetal imaging including both ultrasound and MRI allow for increasingly more specific diagnosis if the radiologist is familiar with specific imaging features and patterns. Early imaging of neonates with suspected central nervous system infection is valuable to enable prompt treatment and differentiate infection from other conditions which can clinically present similarly. Ultrasound is a useful initial modality to screen for abnormalities however MRI with and without contrast remains the optimal examination to characterize infection, evaluate for potential surgical targets, and provide prognostic information.

Bacteria reduce flagellin synthesis to evade microglia-astrocyte-driven immunity in the brain.

The immune response of brain cells to invading bacteria in vivo and the mechanism used by pathogenic bacteria to escape brain immune surveillance remain largely unknown. It is believed that microglia eliminate bacteria by phagocytosis based on in vitro data. Here we find that a small percentage of microglia in the brain engulf neonatal meningitis-causing Escherichia coli (NMEC), but more microglia are activated to produce tumor necrosis factor alpha (TNFα), which activates astrocytes to secrete complement component 3 (C3) involved in anti-bacterial activity. To evade anti-bacterial activity of the immune system, NMEC senses low concentration of threonine in cerebrospinal fluid (CSF) to down-modulate the expression of flagellin and reduce microglial TNFα and astrocyte C3 production. Our findings may help develop strategies for bacterial meningitis treatment.