New and old lessons from a devastating case of neonatal E coli meningitis.

BACKGROUND: Neonatal Escherichia coli (E coli) meningitis results in significant morbidity and mortality. We present a case of a premature infant with extensive central nervous system (CNS) injury from recurrent E coli infection and the non-traditional methods necessary to identify and clear the infection. CASE PRESENTATION: The infant was transferred to our institution's pediatric intensive care unit (PICU) after recurrence of E coli CNS infection requiring neurosurgical intervention. He had been treated for early onset sepsis (EOS) with ampicillin and gentamicin for 10 days followed by rapid development of ampicillin-resistant E coli septic shock and meningitis after discontinuation of antibiotics. Sterility of the CNS was not confirmed at the end of 21 days of cefepime therapy and was subsequently followed by recurrent ampicillin-resistant E coli septic shock and CNS infection. Despite 6 weeks of appropriate therapy with sterility of CSF by traditional methods, he suffered from intractable seizures with worsening hydrocephalus. Transferred to our institution, he underwent endoscopic 3rd ventriculostomy with cyst fenestration revealing purulent fluid and significant pleocytosis. An additional 3 weeks of systemic and intraventricular antibiotics with cefepime and tobramycin were given but a significant CNS neutrophil-predominant pleocytosis persisted (average of ∼ 21,000 cells/mm3). Repeated gram stains, cultures, polymerase chain reaction (PCR) testing, and metagenomic next generation sequencing (NGS) testing of CSF were negative for pathogens but acridine orange stain (AO) revealed numerous intact rod-shaped bacteria. After the addition of ciprofloxacin, sterility and resolution of CSF pleocytosis was finally achieved. CONCLUSION: Neonatal E coli meningitis is a well-known entity but unlike other bacterial infections, it has not proven amenable to shorter, more narrow-spectrum antibiotic courses or limiting invasive procedures such as lumbar punctures. Further, microbiologic techniques to determine CSF sterility suffer from poorly understood limitations leading to premature discontinuation of antibiotics risking further neurologic damage in vulnerable hosts.

Escherichia coli Meningitis in a 72-year-old Woman.

Spontaneous community-acquired meningitis caused by E. coli is rare in the adult population. It is associated with a high risk of morbidity and mortality. We describe a case of a 72-year-old woman who presented with altered mental status and neck stiffness and was found to have E. coli meningitis. Urine cultures grew E. coli, representing a likely source. The E. coli strain was identified as sequence type 73 (E. coli ST73). Her symptoms and laboratory values improved following antibiotic initiation, and she was discharged from the hospital to a rehabilitation facility.

Melatonin Is Neuroprotective in Escherichia coli Meningitis Depending on Intestinal Microbiota.

Avian meningitis Escherichia coli (E. coli) can cause acute bacterial meningitis which threatens poultry health, causes great economic losses in the poultry industry, and has recently been speculated as a potential zoonotic pathogen. Melatonin can counteract bacterial meningitis-induced disruption of the blood-brain barrier (BBB), neuroinflammation, and reduce mortality. There are increasing data showing that melatonin's beneficial effects on bacterial meningitis are associated with intestinal microbiota. In this study, our data showed that melatonin alleviated neurological symptoms, enhanced survival rate, protected the integrity of the BBB, reduced the bacterial load in various tissues and blood, and inhibited inflammation and neutrophil infiltration of brain tissue in an APEC TW-XM-meningitis mice model. The results of 16S rRNA showed that melatonin pretreatment significantly maintained the composition of intestinal microbiota in APEC-meningitis mice. The abundance and diversity of intestinal microbiota were disturbed in APEC TW-XM-meningitis mice, with a decreased ratio of Firmicutes to Bacteroides and an increased the abundance of Proteobacteria. Melatonin pretreatment could significantly improve the composition and abundance of harmful bacteria and alleviate the decreased abundance of beneficial bacteria. Importantly, melatonin failed to affect the meningitis neurologic symptoms caused by APEC TW-XM infection in antibiotic-pretreated mice. In conclusion, the results suggest that melatonin can effectively prevent meningitis induced by APEC TW-XM infection in mice, depending on the intestinal microbiota. This finding is helpful to further explore the specific target mechanism of melatonin-mediated intestinal microbiota in the prevention of and protection against Escherichia coli meningitis.

Bacterial meningitis and COVID-19: a complex patient journey.

A woman in her 70s presented to the emergency department with fever, fluctuating cognition and headache. A detailed examination revealed neurological weakness to the lower limbs with atonia and areflexia, leading to a diagnosis of bacterial meningitis, alongside a concurrent COVID-19 infection. The patient required critical care escalation for respiratory support. After stepdown to a rehabilitation ward, she had difficulties communicating due to new aphonia, hearing loss and left third nerve palsy. The team used written communication with the patient, and with this the patient was able to signal neurological deterioration. Another neurological examination noted a different pattern of weakness to the lower limbs, along with new urinary retention, and spinal arachnoiditis was identified. After more than 10 weeks in the hospital, the patient was discharged. Throughout this case, there were multiple handovers between teams and specialties, all of which were underpinned by good communication and examination to achieve the best care.

Cefalohematoma neonatal infectat per Escherichia coli I meningitis asèptica / Cefalohematoma neonatal infectado por escherichia coli y meningitis aséptica / Escherichia coli-infected neonatal cephalohematoma and aseptic meningitis

INTRODUCCIÓ: Un cefalohematoma és una col·lecció de sang sota el periosti del crani secundària a un traumatisme del part. Afecta entre l'1% I el 2% dels nadons nascuts per un part vaginal I entre el 3% I el 4% dels nascuts mitjançant un part instrumentat. Solen ser benignes I autolimitats, I es resolen espontàniament al cap d'unes setmanes, però alguns casos poden anar acompanyats d'anèmia, hiperbilirubinèmia o fractura cranial, complicar-se amb una calcificació o, rarament, infectar-se. CAS CLINIC: Nounat a terme de 9 dies de vida amb un cefalohematoma present des del naixement que va augmentar de mida després de tenir febre I infectar-se per Escherichia coli, suposadament per l'extensió d'una bacterièmia, I que es va acompanyar d'una meningitis asèptica (pleocitosi) que es va considerar secundària a una osteomielitis per contigüitat. El pacient es va tractar amb antibiòtics I desbridament quirúrgic, I no va tenir seqüeles. COMENTARIS: Cal tenir present que els cefalohematomes, tot I que habitualment tenen un curs autolimitat I una bona evolució, són un lloc potencial d'infecció, I que cal sospitar I descartar la infecció en un pacient amb febre I l'existència prèvia d'un cefalohematoma. S'han descrit casos de meningitis associats a cefalohematoma, però, fins on sabem, només un de meningitis asèptica com el descrit I que es va considerar, a diferència del que presentem, secundària a un retard en la recollida del líquid cefaloraquidi després d'iniciada l'antibioteràpia

INTRODUCCIÓN: Un cefalohematoma es una colección de sangre debajo del periostio del cráneo secundaria a un traumatismo del parto. Afecta a entre el 1% y el 2% de los neonatos nacidos mediante un parto vaginal y a entre el 3% y el 4% de los nacidos mediante un parto instrumentado. Suelen ser benignos, autolimitados y resolverse espontáneamente en semanas, pero en algunos casos se pueden acompañar de anemia, hiperbilirrubinemia o fractura craneal, complicarse con una calcificación o, raramente, infectarse. CASO CLÍNICO: Recién nacido a término de 9 días de vida con un cefalohematoma presente desde el nacimiento que aumentó de tamaño tres haber tenido fiebre e infectarse por Escherichia coli, supuestamente por la extensión de una bacteriemia, y que se acompañó de una meningitis aséptica (pleocitosis) que se consideró secundaria a una osteomielitis por contigüidad. El paciente se trató con antibióticos y desbridamiento quirúrgico y no tuvo secuelas. COMENTARIOS: Debemos tener en cuenta que los cefalohematomas, a pesar de que habitualmente tienen un curso autolimitado y una buena evolución, son un lugar potencial de infección, y que hay que sospechar y descartar la infección en un paciente con fiebre y la existencia de un cefalohematoma previo. Se han descrito algunos casos de meningitis asociados a cefalohematoma, pero hasta donde sabemos solo uno de meningitis aséptica como el descrito y que se consideró, a diferencia del que presentamos, secundaria a un retraso en la recogida del líquido cefalorraquídeo tras el inicio de la antibioterapia

INTRODUCTION: A cephalohematoma is a collection of blood below the periosteum of the skull due to birth trauma. It affects 1-2% of spontaneous vaginal deliveries and 3-4% of instrument-assisted deliveries. It is usually a self-limiting, benign condition which resorbs within weeks. A small proportion of cases can be accompanied by anemia, hyperbilirubinemia or a skull fracture, or be complicated by calcification or rarely by infection. CASE REPORT: 9-day-old full term neonate with a cephalohematoma present at birth that enlarged after the cephalohematoma got infected by Escherichia coli during a septic episode. Aseptic meningitis (pleocytosis) was assumed to be due to contiguous osteomyelitis. The patient was successfully treated with antibiotics and surgical debridement and showed no sequelae. COMMENTS: Clinicians should be aware that even though cephalohematomas are usually a benign, self-limiting condition, they are a potential site of infection. Infection must be suspected and ruled out in a patient with fever and a pre-existing cephalohematoma. A few cases of meningitis accompanying an infected cephalohematoma have been reported, although, to our knowledge, there is only one report of an associated aseptic meningitis. In contrast to the patient we present, in the other reported case lumbar puncture was performed 24 hours after onset of antibiotic treatment, which was suggested as the reason for the cerebrospinal fluid to be sterile

Targeting E. coli invasion of the blood-brain barrier for investigating the pathogenesis and therapeutic development of E. coli meningitis.

Escherichia coli is the most common Gram-negative bacillary organism causing neonatal meningitis. Escherichia coli meningitis remains an important cause of mortality and morbidity, but the pathogenesis of E. coli penetration of the blood-brain barrier remains incompletely understood. Escherichia coli entry into the brain occurs in the meningeal and cortex capillaries, not in the choroid plexus, and exploits epidermal growth factor receptor (EGFR) and cysteinyl leukotrienes (CysLTs) for invasion of the blood-brain barrier. The present study examined whether EGFR and CysLTs are inter-related in their contribution to E. coli invasion of the blood-brain barrier and whether counteracting EGFR and CysLTs is a beneficial adjunct to antibiotic therapy of E. coli meningitis. We showed that (a) meningitis isolates of E. coli exploit EGFR and CysLTs for invasion of the blood-brain barrier, (b) the contribution of EGFR is upstream of that of CysLTs, and (c) counteracting EGFR and CysLTs as an adjunctive therapy improved the outcome (survival, neuronal injury and memory impairment) of animals with E. coli meningitis. These findings suggest that investigation of host factors contributing to E. coli invasion of the blood-brain barrier will help in enhancing the pathogenesis and development of new therapeutic targets for E. coli meningitis in the era of increasing resistance to conventional antibiotics.

Inhibitor discovery for the E. coli meningitis virulence factor IbeA from homology modeling and virtual screening.

Escherichia coli (E. coli) K1 is the most common Gram-negative bacteria cause of neonatal meningitis. The penetration of E. coli through the blood-brain barrier is a key step of the meningitis pathogenesis. A host receptor protein, Caspr1, interacts with the E. coli virulence factor IbeA and thus facilitates bacterial penetration through the blood-brain barrier. Based on this result, we have now predicted the binding pattern between Caspr1 and IbeA by an integrated computational protocol. Based on the predicted model, we have identified a putative molecular binding pocket in IbeA, that directly bind with Caspr1. This evidence indicates that the IbeA (229-343aa) region might play a key role in mediating the bacteria invasion. Virtual screening with the molecular model was conducted to search for potential inhibitors from 213,279 commercially available chemical compounds. From the top 50 identified compounds, 9 demonstrated a direct binding ability to the residues within the Caspr1 binding site on IbeA. By using human brain microvascular endothelial cells (hBMEC) with E. coli strain RS218, four molecules were characterized that significantly attenuated the bacteria invasions at concentrations devoid of cell toxicity. Our study provides useful structural information for understanding the pathogenesis of neonatal meningitis, and have identified drug-like compounds that could be used to develop effective anti-meningitis agents.

A nine-day-old girl with fever. / En ni dager gammel jente med feber.

Nowadays severe illness in neonates is fortunately rare in Norway. However, newborns present with non-specific symptoms, making diagnostics in this age group challenging, and neonatologists need to think broadly in order not to overlook serious illness. We present the case of a nine-day-old who was severely ill when she arrived at hospital. She was born in gestational week 37 after a normal pregnancy. The birth was complicated by shoulder dystocia, rupture of the umbilical cord and fracture of the clavicle. Thereafter she had a normal stay in the maternity ward for three days. At home she appeared healthy and gained weight until she returned to hospital after thirteen hours of poor feeding, irritability and fever. The symptoms turned out to be caused by bacterial meningitis. During the first week of hospitalisation she developed ventriculitis, brain abscesses and sinus vein thrombosis. It was later discovered that she had severely impaired hearing, and thereafter she developed hydrocephalus requiring surgical drainage. The mortality from neonatal bacterial meningitis has dropped from almost 50 % in the 1970s to less than 10 % today, but the morbidity has remained unchanged. It is crucial that clinicians are alert to this diagnosis, as delayed treatment can worsen the prognosis.

Combination therapy with ciprofloxacin and third-generation cephalosporin versus third-generation cephalosporin monotherapy in Escherichia coli meningitis in infants: a multicentre propensity score-matched observational study.

OBJECTIVES: Escherichiacoli is the second cause of bacterial meningitis in neonates. Despite the use for 35 years of third-generation cephalosporins (3GCs), high morbidity and mortality rates with E. coli meningitis continue to occur. Because ciprofloxacin has good microbiologic activity against E. coli and good penetration in cerebrospinal fluid and brain, some authors have suggested adding ciprofloxacin to a 3GC regimen. The objective of this study was to assess combining 3GCs with ciprofloxacin versus 3GCs alone in a cohort of infants with E. coli meningitis. METHODS: We included all cases of E. coli meningitis diagnosed in infants <12 months of age that were prospectively collected through the French paediatric meningitis surveillance network between 2001 and 2016. The main outcome was the proportion of short-term neurologic complications with versus without ciprofloxacin. The analysis was conducted retrospectively by multivariable regression and propensity score (PS) analysis. RESULTS: Among the 367 infants enrolled, 201 (54.8%) of 367 had ciprofloxacin and 3GC cotreatment and 166 (45.2%) of 367 only a 3GC. Median age and weight were 15 days (range, 1-318 days) and 3.42 kg (range, 0.66-9.4 kg). A total of 86 (23.4%) of 367 infants presented neurologic complications (seizures, strokes, empyema, abscesses, hydrocephalus, arachnoiditis); 57 received ciprofloxacin cotreatment. Complications were associated with ciprofloxacin cotreatment on multivariable analysis (odds ratio (OR) = 1.9; 95% confidence interval (CI), 1.1-3.4) and PS analysis (OR = 1.9; 95% CI, 1.1-3.3). Mortality rate did not differ with and without ciprofloxacin: 22 (10.9%) of 201 versus 16 (9.6%) of 166 deaths (OR = 0.7; 95% CI, 0.3-1.6; PS analysis). CONCLUSIONS: Ciprofloxacin added to 3GCs at least offers no advantage for neurologic outcome and mortality in infants with E. coli meningitis.

Full Neurological Recovery From Escherichia coli Meningitis Associated With Near-Death Experience.

A 54-year-old otherwise healthy man presented with altered mental status. On admission, the patient was confused and agitated, with a Glasgow Coma Scale (GCS) score of 11, suggesting moderate brain injury. He was sedated, placed on a ventilator, and started on tobramycin and ceftazidime for presumed bacterial meningitis, but switched to ceftriaxone once cultures returned as Escherichia coli. During his 8-day hospitalization, his mental status fluctuated from confused to nonresponsive, with GCS scores between 6 and 11. Although E. coli meningitis has a high rate of neurological complications and death, this patient recovered completely without any deficits, and recalled an elaborate near-death experience that occurred during his coma. This case highlights the importance of studying near-death experiences occurring during compromised brain function to further our understanding of the brain and consciousness.

IQGAP1 Mediates Hcp1-Promoted Escherichia coli Meningitis by Stimulating the MAPK Pathway.

Escherichia coli-induced meningitis remains a life-threatening disease despite recent advances in the field of antibiotics-based therapeutics, necessitating continued research on its pathogenesis. The current study aims to elucidate the mechanism through which hemolysin-coregulated protein 1 (Hcp1) induces the apoptosis of human brain microvascular endothelial cells (HBMEC). Co-immunoprecipitation coupled with mass spectrometric (MS) characterization led to the identification of IQ motif containing GTPase activating protein 1 (IQGAP1) as a downstream target of Hcp1. IQGAP1 was found to be up-regulated by Hcp1 treatment and mediate the stimulation of HBMEC apoptosis. It was shown that Hcp1 could compete against Smurf1 for binding to IQGAP1, thereby rescuing the latter from ubiquitin-dependent degradation. Subsequent study suggested that IQGAP1 could stimulate the MAPK signaling pathway by promoting the phosphorylation of ERK1/2, an effect that was blocked by U0126, an MAPK inhibitor. Furthermore, U0126 also demonstrated therapeutic potential against E. coli meningitis in a mouse model. Taken together, our results suggested the feasibility of targeting the MAPK pathway as a putative therapeutic strategy against bacterial meningitis.

Does antimicrobial usage before meningitis lead to a higher risk of adult postsurgical Acinetobacter baumannii meningitis than that of Enterobacteriaceae meningitis?

Acinetobacter baumannii and Enterobacteriaceae are two pathogens responsible for postneurosurgical meningitis. The aim of this retrospective study was to evaluate the factors that influenced the outcomes in patients with postneurosurgical meningitis caused by A. baumannii and Enterobacteriaceae. Patients with post-surgical meningitis were identified from infection control committee charts between 2007 and 2015. Subjects over 16 years old who had positive cerebral spinal fluid cultures for A. baumannii or Enterobacteriaceae were enrolled in the study. Clinical and laboratory data for 30 patients with A. baumannii meningitis were compared with those of 12 patients with Enterobacteriaceae meningitis. The mean age of patients was 51.9 years and 57.1% were male. Eleven patients had comorbidities, the most common being diabetes mellitus. Most patients were due to intracranial haemorrhage (78.6%). The rate of the patients who received an appropriate antimicrobial therapy was 35.7%, and the crude mortality rate was 64.3%. In univariate analysis, previous antibiotic use, an infection before meningitis and mechanical ventilation had an increased risk of A. baumannii meningitis. Moreover, intrathecal antimicrobial use, inappropriate empirical antimicrobial use, antimicrobial resistance and alanine aminotransferase elevation were significantly higher in patients with A. baumannii meningitis than in those with Enterobacteriaceae meningitis. Antimicrobial use before meningitis (8.84 times) and mechanical ventilation (7.28 times) resulted in an increased risk of A. baumannii meningitis. None of the results affected 30-day mortality. Avoidance of unnecessarily prolonged antimicrobial usage may help to prevent a selection of A. baumannii.

[Clinical features of childhood purulent meningitis caused by Escherichia coli and Streptococcus pneumoniae: a comparative analysis].

OBJECTIVE: To investigate the differences in clinical features of childhood purulent meningitis (PM) caused by Escherichia coli and Streptococcus pneumoniae, and to provide help for the selection of antibiotics for PM children with unknown etiology. METHODS: A retrospective analysis was performed for the clinical data of children with PM caused by Escherichia coli (12 children) or Streptococcus pneumoniae (15 children). RESULTS: Compared with the Streptococcus pneumoniae infection group, the Escherichia coli infection group had a significantly higher proportion of children with an age of onset of <3 months and a significantly higher incidence rate of convulsion, but significantly lower incidence rates of severe fever (>39°C) and disturbance of consciousness and a significantly lower proportion of children with an increased leukocyte count at diagnosis (>12×10(9)/L). The results of routine cerebrospinal fluid test and biochemical examinations showed no significant differences between the two groups. Escherichia coli and Streptococcus pneumoniae were resistant to cephalosporins and had a sensitivity to chloramphenicol more than 90%. Escherichia coli was fully sensitive to meropenem and Streptococcus pneumoniae was fully sensitive to vancomycin. CONCLUSIONS: PM caused by Escherichia coli and Streptococcus pneumoniae has different clinical features. As for PM children with severe fever, disturbance of consciousness, and an increased leukocyte count, the probability of Streptococcus pneumoniae infection should be considered. For PM children with an age of onset of <3 months, medium- and low-grade fever, frequent convulsions, and a leukocyte count of <12×10(9)/L, the probability of Escherichia coli infection should be considered.

[Two cases of neonatal meningitis after new gentamicin dosing guidelines]. / To tilfaelde af neonatal meningitis efter indførelse af nyt gentamicinregime

Neonates with suspected or proven sepsis are treated with ampicillin and until recently with 5 mg gentamicin/kg every 24 h. New guidelines recommend the same gentamicin dose, but with longer intervals depending on gestational age. Two neonates receiving gentamicin every 48 h improved initially, but both deteriorated again before the second dose. In both infants ampicillin-resistant but gentamicin-sensitive Escherichia coli was found. In one of the infants a resistant/less sensitive E. coli strain was also found in the cerebrospinal fluid. The rationale for the new dosing guidelines is discussed.

Repositioning of Memantine as a Potential Novel Therapeutic Agent against Meningitic E. coli-Induced Pathogenicities through Disease-Associated Alpha7 Cholinergic Pathway and RNA Sequencing-Based Transcriptome Analysis of Host Inflammatory Responses.

Neonatal sepsis and meningitis (NSM) remains a leading cause worldwide of mortality and morbidity in newborn infants despite the availability of antibiotics over the last several decades. E. coli is the most common gram-negative pathogen causing NSM. Our previous studies show that α7 nicotinic receptor (α7 nAChR), an essential regulator of inflammation, plays a detrimental role in the host defense against NSM. Despite notable successes, there still exists an unmet need for new effective therapeutic approaches to treat this disease. Using the in vitro/in vivo models of the blood-brain barrier (BBB) and RNA-seq, we undertook a drug repositioning study to identify unknown antimicrobial activities for known drugs. We have demonstrated for the first time that memantine (MEM), a FDA-approved drug for treatment of Alzheimer's disease, could very efficiently block E. coli-caused bacteremia and meningitis in a mouse model of NSM in a manner dependent on α7 nAChR. MEM was able to synergistically enhance the antibacterial activity of ampicillin in HBMEC infected with E. coli K1 (E44) and in neonatal mice with E44-caused bacteremia and meningitis. Differential gene expression analysis of RNA-Seq data from mouse BMEC infected with E. coli K1 showed that several E44-increased inflammatory factors, including IL33, IL18rap, MMP10 and Irs1, were significantly reduced by MEM compared to the infected cells without drug treatment. MEM could also significantly up-regulate anti-inflammatory factors, including Tnfaip3, CISH, Ptgds and Zfp36. Most interestingly, these factors may positively and negatively contribute to regulation of NF-κB, which is a hallmark feature of bacterial meningitis. Furthermore, we have demonstrated that circulating BMEC (cBMEC) are the potential novel biomarkers for NSM. MEM could significantly reduce E44-increased blood level of cBMEC in mice. Taken together, our data suggest that memantine can efficiently block host inflammatory responses to bacterial infection through modulation of both inflammatory and anti-inflammatory pathways.

Efficacy of Ceftaroline Fosamil against Escherichia coli and Klebsiella pneumoniae strains in a rabbit meningitis model.

In this study, the efficacy of ceftaroline fosamil was compared with that of cefepime in an experimental rabbit meningitis model against two Gram-negative strains (Escherichia coli QK-9 and Klebsiella pneumoniae 1173687). The penetration of ceftaroline into inflamed and uninflamed meninges was also investigated. Both regimens were bactericidal, but ceftaroline fosamil was significantly superior to cefepime against K. pneumoniae and E. coli in this experimental rabbit meningitis model (P < 0.0007 against K. pneumoniae and P < 0.0016 against E. coli). The penetration of ceftaroline was approximately 15% into inflamed meninges and approximately 3% into uninflamed meninges.

Community-acquired CTX-M-15-type ESBL-producing Escherichia coli meningitis: a case report and literature review.

In this report, a case of community-acquired acute bacterial meningitis (CA-ABM) caused by CTX-M-15-producing Escherichia coli in an elderly male patient was presented in the light of literature. Cultures of cerebrospinal fluid, blood, ear discharge, and stool samples yielded CTX-M-15-producing E. coli in-vitro, which was resistant to the extended-spectrum cephalosporins and ciprofloxacin and susceptible to imipenem, meropenem and amikacin. Meningitis was treated with parenteral meropenem plus parenteral and intraventricular amikacin administration. Since bacterial meningitis is a life-threatening infection, empiric antibiotic therapy with carbapenem can be started before the culture results are obtained, mainly in areas where the ESBL epidemiology is well known.

[Clinical analysis of 31 cases of neonatal purulent meningitis caused by Escherichia coli].

OBJECTIVE: Neonatal purulent meningitis is a severe infection responsible for high mortality and disabling sequelae. Escherichia coli is the main pathogen of neonatal purulent meningitis. This study explored the clinical characteristics and antibiotic resistance of Escherichia coli-induced neonatal meningitis. METHODS: A retrospective chart review was performed. A total of 31 cases of neonatal purulent meningitis caused by Escherichia coli were identified in the neonatal intensive care unit between January 1, 2001 and December 31, 2011. The clinical characteristics and antibiotic sensitivity test results were analyzed. RESULTS: Fever, poor feeding, lethargy and seizure were common clinical signs of neonatal purulent meningitis caused by Escherichia coli. Acute complications mainly included hyponatremia (17 cases), hydrocephalus (8 cases), subdural collection (2 cases), ventriculitis (2 cases) and cerebral infarction (1 case). Thirty neonates (97%) had increased CRP levels. Of the 31 patients, 14 cases were cured and 12 had adverse outcomes (5 patients died during hospitalization). Escherichia coli strains were resistant (>50%) to commonly used penicillins and cephalosporins between 2007 and 2011, presenting significantly higher resistance rates than between 2001 and 2006. The detection rate of extended spectrum ß-lactamases (ESBLs)-producing strains between 2007 and 2011 increased significantly compared with between 2001 and 2006 (57% vs 0). CONCLUSIONS: The clinical manifestations of neonatal purulent meningitis caused by Escherichia coli are non specific. The outcome is poor. Monitoring of CRP levels is valuable for the early diagnosis of neonatal purulent meningitis. The antimicrobial resistance rates of Escherichia coli are increasing, especially to cephalosporins. The percentage of ESBLs-producing strains is increasing over the years.

[Therapeutic strategies for Escherichia coli neonatal meningitis]. / Stratégies thérapeutiques des méningites néonatales à Escherichia coli.

Outcome of early and late onset E. coli neonatal meningitis is poor with 12% (term infant) to 18% (premature infant) mortality rates. Early complications are cerebral abscesses, ventriculitis and ischemo-haemorragic cerebral lesions. Long term sequelae, particularly neurosensorial [14-17%] and neurodevelopmental [10-17%] are frequent. Delayed or unadapted antibiotic treatment is associated with an excess of complications. Main risk factors are hemodynamic failure, apnea, seizures, hypoglycorachia and abnormal EEG. Antibiotics must be started as soon as possible with a third generation cephalosporin (3GC). Cefotaxime is the most largely 3GC used with good tolerance and the most appropriate Pk/PD parameters, frequently in association with ciprofloxacin. Experimentally, neuroprotective drugs were recently proposed to improve prognosis such as inflammatory inhibitors, leakage bacterial components inhibitors, PMN penetration inhibitors in CSF, apoptosis regulators. Clinically protective effect of corticosteroids is discussed. Ciprofloxacin has an intrinsic anti-inflammatory activity and seems interesting to use in addition to conventional antibiotherapy during the first days of treatment. Prevalence of 3GC-resistant E. coli is 5% in the vaginal flora of pregnant women in some hospitals in France; this rate leads to reconsider first line antibiotic treatment and to switch cephalosporin with meropenem in neonates with confirmed gram negative bacilli or 3GC-resistant E. coli meningitis.