Chemotaxis and Shorter O-Antigen Chain Length Contribute to the Strong Desiccation Tolerance of a Food-Isolated Cronobacter sakazakii Strain

Cronobacter sakazakii is an opportunistic pathogen causing a lethality rate as high as 80% in infants. Desiccation tolerance ensures its survival in powdered infant formula (PIF) and contributes to the increased exposure to neonates, resulting in neonatal meningitis, septicemia, and necrotizing enterocolitis. This study showed that a food-isolated C. sakazakii G4023 strain exhibited a stronger desiccation tolerance than C. sakazakii ATCC 29544 strain. Considering the proven pathogenicity of G4023, it could be a big threat to infants. Transcriptome and proteome were performed to provide new insights into the desiccation adaptation mechanisms of G4023. Integrated analyses of these omics suggested that 331 genes were found regulated at both transcriptional and protein levels (≥2.0- and ≥1.5-fold, respectively). Deletion of chemotaxis system encoded genes cheA and cheW resulted in decreased tolerance in both short- and long-term desiccation. Reduced O-antigen chain length contributed to the biofilm formation and desiccation tolerance in the short term rather than the long term. In addition, biosynthesis of flagella, arginine and its transport system, and Fe/S cluster were also observed regulated in desiccated G4023. A better understanding of desiccation adaptation mechanisms of G4023 could in turn guide the operations during production and preservation of PIF or other food to reduce survival odds of G4023 and lower its exposure to get to infants.

Bacteriological profile, antibiotic susceptibility pattern and other factors related to neonatal meningitis: A cross-sectional hospital-based study from West Bengal

Background: Neonatal sepsis and meningitis is an important cause of neonatal mortality and morbidity especially in the developing countries. Bacteriological profile of meningitis and antibiotic sensitivity pattern may vary from one region to another. Aims and Objectives: We have planned this study to know the etiological agent of neonatal meningitis with its antibiotic sensitivity profile and to evaluate some other associated risk factors of meningitis. Materials and Methods: This observational, cross-sectional study was done for a period of 1 year in the SNCU and NICU of a district Medical College of West Bengal in neonates presented with clinical sepsis and meningitis. Sepsis screen, blood culture, cerebrospinal fluid (CSF) study, and culture sensitivity was done and recorded along with demographic data, clinical presentation, outcome, and other associated factors. Results: We found meningitis in 55 neonates out of 250 clinical sepsis. CSF culture was positive in 42 cases with Escherichia coli (30.9%), Klebsiella (26.1%), Staphylococcus aureus (16.6%), Acinetobacter (14.2%) and Coagulase negative Staphylococcus (CoNS 11.9%) as prevalent organism. E. coli and Klebsiella were mostly sensitive to Amikacin, Levofloxacin, and Colistin whereas less sensitive to Cefotaxime, Pipercilin-tazobactam or Meropenem and Acinetobacter showed good sensitivity only to Levofloxacin. Among the gram-positive organism, S. aureus and CoNS were only sensitive to Linezolid, Vancomycin, and Teicoplanin. Conclusion: This type of study should help to make a proper antibiotic policy for an institution so that the empirical first-line antibiotic can be started with good effect in cases of neonatal sepsis and meningitis before the arrival of culture sensitivity report.

What Flips the Switch? Signals and Stress Regulating Extraintestinal Pathogenic Escherichia coli Type 1 Fimbriae (Pili)

Pathogens are exposed to a multitude of harmful conditions imposed by the environment of the host. Bacterial responses against these stresses are pivotal for successful host colonization and pathogenesis. In the case of many E. coli strains, type 1 fimbriae (pili) are an important colonization factor that can contribute to diseases such as urinary tract infections and neonatal meningitis. Production of type 1 fimbriae in E. coli is dependent on an invertible promoter element, fimS, which serves as a phase variation switch determining whether or not a bacterial cell will produce type 1 fimbriae. In this review, we present aspects of signaling and stress involved in mediating regulation of type 1 fimbriae in extraintestinal E. coli; in particular, how certain regulatory mechanisms, some of which are linked to stress response, can influence production of fimbriae and influence bacterial colonization and infection. We suggest that regulation of type 1 fimbriae is potentially linked to environmental stress responses, providing a perspective for how environmental cues in the host and bacterial stress response during infection both play an important role in regulating extraintestinal pathogenic E. coli colonization and virulence.

Early neonatal respiratory distress revealing meningitis caused by Streptococcus pneumoniae serotype 17F: a case report

Background: Streptococcus pneumoniae (S. pneumoniae) is the first leading cause of invasive diseases such as meningitis, bacteremia and pneumoniae in children. In this case we report an early neonatal respiratory distress revealing meningitis caused byS. pneumoniae Serotype 17F through vertical transmission, in the newborn of 3 hours of live. Case description: A male late preterm newborn was born by vaginal delivery at a gestational age of 34 weeks. At 3 hours of life, he was admitted for early moderate neonatal respiratory distress in the Neonatal Medicine and Resuscitation Service.Cerebrospinal fluid culture yielded S. pneumoniae belonging to serotype 17F while the blood culture was negative. The same pneumococcal serotype was recovered from the high vaginal swab of the mother. Both isolates were found susceptible to all tested antibiotics except tetracycline and chloramphenicol to which the strain was resistant. Antibiotherapy management of the child included ceftriaxone at 150mg/kg/day for 21 days, in combination with gentamycin at 5 mg/kg/day for 5 days. ciprofloxacin was added at 40mg/kg/day in two doses for a period of three weeks as the baby presented a hydrocephalus. Conclusion: This finding shows that clinical manifestations of neonatal pneumococcal meningitis may be atypical and/or misleading. Keywords: Streptococcus pneumoniae; neonatal meningitis; respiratory distress.

GBS-SBG - GBS Serotyping by Genome Sequencing

Group B Streptococcus (GBS; Streptococcus agalactiae ) is the most common cause of neonatal meningitis and a rising cause of sepsis in adults. Recently, it has also been shown to cause foodborne disease. As with many other bacteria, the polysaccharide capsule of GBS is antigenic, enabling its use for strain serotyping. Recent advances in DNA sequencing have made sequence-based typing attractive (as has been implemented for several other bacteria, including Escherichia coli , Klebsiella pneumoniae species complex, Streptococcus pyogenes , and others). For GBS, existing WGS-based serotyping systems do not provide complete coverage of all known GBS serotypes (specifically including subtypes of serotype III), and none are simultaneously compatible with the two most common data types, raw short reads and assembled sequences. Here, we create a serotyping database (GBS-SBG, GBS Serotyping by Genome Sequencing), with associated scripts and running instructions, that can be used to call all currently described GBS serotypes, including subtypes of serotype III, using both direct short-read- and assembly-based typing. We achieved higher concordance using GBS-SBG on a previously reported data set of 790 strains. We further validated GBS-SBG on a new set of 572 strains, achieving 99.8% concordance with PCR-based molecular serotyping using either short-read- or assembly-based typing. The GBS-SBG package is publicly available and will hopefully accelerate and simplify serotyping by sequencing for GBS.

O -Acetylation of Capsular Polysialic Acid Enables Escherichia coli K1 Escaping from Siglec-Mediated Innate Immunity and Lysosomal Degradation of E. coli -Containing Vacuoles in Macrophage-Like Cells

Escherichia coli K1 is a leading cause of neonatal meningitis. The mortality and morbidity of this disease remain significantly high despite antibiotic therapy.

Therapeutic Drug Monitoring of Moxifloxacin to Guide Treatment of Mycoplasma hominis Meningitis in an Extremely Preterm Infant

Mycoplasma hominis (M hominis) is a rare cause of neonatal bacterial meningitis. Treatment can be challenging because of M hominis' intrinsic antibiotic resistance and the difficulty in accessing antimicrobial susceptibility testing. In this report, we describe an extremely preterm male infant with seizures who had a subsequent diagnosis of M hominis meningitis. Because of severity of illness, doxycycline (4 mg/kg IV every 24 hours) and moxifloxacin (5 mg/kg IV every 24 hours) were started empirically. Repeat cerebrospinal fluid cultures were negative and showed decreasing pleiocytosis. Given the concentration-dependent killing of moxifloxacin and concern for endovascular infection from a concomitant cerebral venous sinus thrombosis, serum concentrations of moxifloxacin were obtained to estimate pharmacokinetic and pharmacodynamic parameters. These were compared to the targets described in other case reports of M hominis meningitis. The maximum serum concentration (Cmax) was 2.5 mg/L, volume of distribution was 2.2 L/kg, clearance was 0.18 L/kg/hr, terminal half-life was 8.6 hours, and area-under-the-concentration-time curve (AUC) was 28.1 mg•hr/L. Using the range of minimum inhibitory concentrations (MICs) reported in the literature, the estimated Cmax/MIC for this patient was 21 to 158 (target Cmax/MIC: >10) and AUC/MIC was 234 to 1757 (target AUC/MIC: ≥100). Doxycycline and moxifloxacin were continued for 6 weeks. No adverse events to moxifloxacin or doxycycline were observed in the NICU. This report describes the successful treatment of M hominis neonatal meningitis and adds to the knowledge of pharmacokinetic and pharmacodynamic parameters of moxifloxacin in neonates. Additional data will help to confirm the role for routine therapeutic drug monitoring of moxifloxacin in neonates.

Diagnostic Utility of Cerebrospinal Fluid Procalcitonin in Neonatal Meningitis

We aimed to study the diagnostic utility of cerebrospinal fluid (CSF) procalcitonin in neonates with meningitis. All the neonates with sepsis who qualified for lumbar puncture were prospectively evaluated. The neonates were classified as Meningitis and No meningitis group based on predefined criteria. CSF procalcitonin was estimated in these neonates along with cytological and biochemical parameters. A total of 113 neonates were included in the study with 29 in meningitis group and 84 in no meningitis group. The median procalcitonin levels was higher in babies with meningitis as compared to those without meningitis [0.194 (0.034 - 0.534) in meningitis group vs 0.012 (0.012-0.012) ng/ml in no meningitis group, p< 0.001]. The area under curve (AUC) for CSF procalcitonin was 0.867 (0.77 -0.95) and at a cut off level of 0.120 ng/ml CSF procalcitonin had a sensitivity of 83%, specificity of 84% and positive and negative predictive likelihood ratios of 5.35 and 0.20 respectively for the diagnosis of meningitis.Conclusion: CSF procalcitonin has a good diagnostic accuracy similar to other parameters in the diagnosis of neonatal meningitis and can be considered as an additional diagnostic marker particularly, when CSF culture is negative and cytochemical analysis is inconclusive.Trial registration number and date: CTRI/2018/09/015720 ; 14/09/2018

The Contribution of Lumbar Puncture in Neonatal Infections - About 206 cases

Background: Neonatal meningitis is a serious infection, no clinico-biological score has been established to accurately identify neonates at high risk of developing neonatal meningitis.Objective: The aim of this work is to clarify the place of lumbar puncture in neonatal infections and to identify the predictive factors of meningeal localization in case of neonatal infection.Materials and methods: This is a prospective study of 861 observations of newborns hospitalized in the pediatric department of Mohammed V Hospital, CHU of Tangier, during a 14-month period from 1January 2019 to 29 February 2020. Among these patients the diagnosis of neonatal infection (NNI) was retained in 473 cases. Initial lumbar puncture was performed in 206 cases (43%). We included neonates aged 0 to 28 days, suspected of NNI, who had a lumbar puncture. Neonates treated as carriers of neonatal infection without sufficient anamnestic and clinical evidence and with an inconclusive or unperformed biological workup were excluded from the study.Results: During the study period, 861 newborns were hospitalized and the diagnosis of neonatal infection was retained in 473 cases, a rate of 55%, and the initial lumbar puncture was performed in 206 cases (43%). 61 newborns were diagnosed with neonatal meningitis, with fever in 76% of cases, 85% with convulsions, hypotonia and/or refusal to suckle in 63% of cases, and CRP >25mg/l in 67% of newborns.Conclusion: Lumbar puncture is the only diagnostic means of meningitis. Indeed, the indication of this procedure should not be systematic, but it should be dictated by the careful and simultaneous analysis of the anamnestic, clinical and biological criteria evocative of the infection and its meningeal localization in order to diagnose meningitis early and treat it correctly. The need to establish scores combining these different parameters, in order to accurately identify newborns at high risk of developing neonatal meningitis