The Clinical Characteristics and Therapeutic Outcomes of Escherichia Coli Meningitis in Adults.

BACKGROUND: To examine the clinical characteristics and therapeutic outcome of Escherichia (E.) coli adult bacterial meningitis (ABM). METHODS: The demographic data, clinical and laboratory features and therapeutic outcome of 25 E. coli ABM patients were examined retrospectively. The clinical features of the reported E. coli ABM cases were also included for analysis. RESULTS: The 25 E. coli ABM patients included 12 women and 13 men, aged 33-78 years (mean= 59.9). Of these 25 patients, 13 had a postneurosurgical state as the underlying condition. As to the underlying medical conditions, diabetes mellitus was the most common, found in 9 of the 25 cases. Of the clinical manifestation, severe neurologic manifestations including altered consciousness (19), hydrocephalus (10), seizure (7) acute/subacute cerebral infarct (5), brain abscess (2), subdural empyema (1) and spinal abscess (1) were found, and the other clinical features included fever (21), septic shock (8), bacteremia (6) and hyponatremia (3). With treatment, the mortality rate was more than 44.0% and the presence of septic shock was a significant prognostic factor. With literature review, 29 community-acquired and 12 postneurosurgical E. coli ABM cases were enrolled, and severe neurologic manifestation and high mortality rate were also found. CONCLUSIONS: This preliminary overview of E. coli ABM revealed the underlying conditions, severe neurologic manifestation and high mortality rate. Further large-scale, prospective study is needed for a better delineation of this specific infectious syndrome of adult E. coli meningitis.

Mesenchymal stem cells transplantation attenuates brain injury and enhances bacterial clearance in Escherichia coli meningitis in newborn rats.

OBJECTIVE: Neonatal meningitis caused by Escherichia coli results in significant mortality and neurological disabilities, with few effective treatments. Recently, we demonstrated that human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) transplantation attenuated E. coli-induced severe pneumonia, primarily by reducing inflammation and enhancing bacterial clearance. This study aimed to determine whether intraventricular transplantation of hUCB-MSCs attenuated the brain injury in E. coli meningitis in newborn rats. METHODS: Meningitis without concomitant bacteremia was induced by intraventricular injection of 5 × 102 colony forming units of K1 (-) E. coli in rats at postnatal day (P)11, and hUCB-MSCs (1 × 105) were transplanted intraventricularly 6 h after induction of meningitis. Antibiotics was started 24 h after modeling. RESULT: Meningitis modeling induced robust proliferation of E. coli in the cerebrospinal fluid and increased mortality in rat pups, and MSC transplantation significantly reduced this bacterial growth and the mortality rate. Impaired sensorimotor function in the meningitis rats was ameliorated by MSCs injection. MSCs transplantation also attenuated meningitis caused brain injury including cerebral ventricular dilatation, brain cell death, reactive gliosis, and inflammatory response. CONCLUSION: Intraventricular transplantation of hUCB-MSCs significantly improved survival and attenuated the brain injury via anti-inflammatory and antibacterial effects in experimental neonatal E. coli meningitis.

Human Meningitis-Associated Escherichia coli.

Escherichia coli is the most common Gram-negative bacillary organism causing meningitis, and E. coli meningitis continues to be an important cause of mortality and morbidity throughout the world. Our incomplete knowledge of its pathogenesis contributes to such mortality and morbidity. Recent reports of E. coli strains producing CTX-M-type or TEM-type extended-spectrum ß-lactamases create a challenge. Studies using in vitro and in vivo models of the blood-brain barrier have shown that E. coli meningitis follows a high degree of bacteremia and invasion of the blood-brain barrier. E. coli invasion of the blood-brain barrier, the essential step in the development of E. coli meningitis, requires specific microbial and host factors as well as microbe- and host-specific signaling molecules. Blockade of such microbial and host factors contributing to E. coli invasion of the blood-brain barrier is shown to be efficient in preventing E. coli penetration into the brain. The basis for requiring a high degree of bacteremia for E. coli penetration of the blood-brain barrier, however, remains unclear. Continued investigation on the microbial and host factors contributing to a high degree of bacteremia and E. coli invasion of the blood-brain barrier is likely to identify new targets for prevention and therapy of E. coli meningitis.

Superior effect of hypertonic saline over mannitol to attenuate cerebral edema in a rabbit bacterial meningitis model.

OBJECTIVE: Adjunctive therapies that reduce the cerebral edema in bacterial meningitis include osmotic agents. There is a lack of information comparing mannitol vs. hypertonic saline as an osmotic agent for adjunctive therapy of bacterial meningitis. We attempted to elucidate the impact of hypertonic saline in cerebral edema in the setting of bacterial meningitis as well as to explore potential mechanisms of action. DESIGN: Randomized controlled in vivo study. SETTING: University research laboratory. SUBJECTS: Rabbits. INTERVENTIONS: A rabbit model of bacterial meningitis was used comparing 3% hypertonic saline with 20% mannitol as adjunctive therapy. MEASUREMENTS AND MAIN RESULTS: Adjunctive 3% hypertonic saline treatment persistently elevated mean arterial pressure as compared with the model or ampicillin group (p < .01). Although both 20% mannitol and 3% hypertonic saline efficiently elevated serum osmolality for almost 5 hrs (p < .01), 20% mannitol lowered intracranial pressure for only a short time (<2 hrs) and did not elevate cerebral perfusion pressure. Three percent hypertonic saline treatment efficiently lowered intracranial pressure and elevated cerebral perfusion pressure for almost 5 hrs (p < .01). Furthermore, 3% hypertonic saline treatment efficiently elevated serum Na+ concentration for >5 hrs (p < .01). Three percent hypertonic saline treatment was superior to 20% mannitol in lowering leukocyte number and protein content in cerebrospinal fluid (p < .01). Three percent hypertonic saline treatment reduced water content and Evans blue incorporation in the brain (p < .01). Three percent hypertonic saline treatment inhibited aquaporin 4 expression (p < .01) and attenuated pathologic brain damage more efficiently compared with adjuvant 20% mannitol treatment (p < .01). CONCLUSIONS: Adjunctive 3% hypertonic saline treatment significantly elevated mean arterial pressure, reduced intracranial pressure, greatly improved cerebral perfusion pressure, inhibited brain aquaporin 4 expression, reduced cerebral edema, and attenuated brain damage with a superior effect over 20% mannitol in a rabbit bacterial meningitis model.

New diagnostic and therapeutic options in bacterial meningitis in infants and children.

Bacterial meningitis continues to be an important cause of mortality and morbidity in neonates and children through the world. Current strategies to prevention and therapy of bacterial meningitis are compromised by incomplete understanding of the pathogenesis, emergence of antimicrobial resistant microorganisms and lack of simple diagnostic tools in resource-limited settings. Successful prevention and treatment of bacterial meningitis requires the knowledge on epidemiology including prevalence of antimicrobial resistant pathogens, pathogenesis of meningitis, and pharmacokinetics and pharmacodynamics of antimicrobial agents. The introduction of the protein conjugate vaccines against Haemophilus influenzae type b, Streptococcus pneumoniae and Neisseria meningitidis has changed the epidemiology of bacterial meningitis. Suspected bacterial meningitis is a medical emergency and requires empiric antimicrobial therapy without delay, but recognition of pathogens with increasing resistance to antimicrobial agents is an important factor in selection of empiric antimicrobial regimen. A more complete knowledge on the pathogenesis of meningitis is likely to help in development of new diagnostic and therapeutic options for infants and children with bacterial meningitis.

[Clinical outcome and bacterial characteristics of 99 Escherichia coli meningitis in young infants]. / Méningite à Escherichia coli de l'enfant : analyse descriptive clinique et microbiologique de 99 cas.

OBJECTIVE: To conduct a descriptive analysis of clinical, biological and prognostic aspects of Escherichia coli meningitis in young infants. METHODS: Clinical and biological data on young infants diagnosed with neonatal E. coli meningitis (NECM) between 1988 and 2004 were collected retrospectively and analyzed with respect to the isolates'phenotypic and genotypic characteristics. The molecular analyses focused on the phylogenetic group, the sequence-O-type, and genetic virulence traits. The virulence of lethal strains was tested in a newborn rat meningitis model. RESULTS: The median age of the 99 children analyzed was 10 days (0 to 90 days), and 83 of the patients were newborns. Thirty-three children were premature. Hyper- or hypothermia was the most frequent clinical sign at admission. Intercurrent urinary tract infection was present in 28% of cases, all over 6 days of age. 81% of blood cultures were positive. The CSF cytology was abnormal in 97% of cases. Twelve hours after admission, 34% of infants were transferred to intensive care. One-third of transfontanellar ultrasound scans done on admission were abnormal. CSH sterilization was slow in 15 % of cases, despite appropriate antibiotic therapy. The use of ciprofloxacin was associated with more rapid CSF sterilization (94 % vs 77 %, p=0.03). Six children relapsed. The average follow-up was eight months, and 21 % of children had sequelae. The case lethality rate was 14%. Fatal outcome was associated with signs of septic shock (57% vs 3%, p<10(-4)) and neurological failure (76% vs 19%, p<10(-4)) within the first 24 hours, and with abnormalities on the first ultrasound scan (63% vs 27%, p=0.03). The risk of death was higher among children infected by strains belonging to unusual sequence-O-types (50% vs 18%, p=0.01), which harbored fewer virulence factors (4.8 vs 5.9, p<10(-4)). Only aerobactin was less frequent in lethal strains (71 % vs 94%, p=0.02). Strains belonging to unusual sequence-O-types and that were lethal in the animal model induced a significantly lower level of bacteremia than strains belonging to frequent sequence-O-types (p<0.001). CONCLUSION: E. coli meningitis remains highly lethal in infants. Clinical and molecular analyses showed a link between lethality and infrequent sequence-O-types. The avirulence of these strains in animal models suggests that fatal outcome could be due to host susceptibility more than to strain virulence.

Prevention and cure of systemic Escherichia coli K1 infection by modification of the bacterial phenotype.

Escherichia coli is a common cause of meningitis and sepsis in the newborn infant, and the large majority of isolates from these infections produce a polysialic acid (PSA) capsular polysaccharide, the K1 antigen, that protects the bacterial cell from immune attack. We determined whether a capsule-depolymerizing enzyme, by removing this protective barrier, could alter the outcome of systemic infection in an animal model. Bacteriophage-derived endosialidase E (endoE) selectively degrades the PSA capsule on the surface of E. coli K1 strains. Intraperitoneal administration of small quantities of recombinant endoE (20 micro g) to 3-day-old rats, colonized with a virulent strain of K1, prevented bacteremia and death from systemic infection. The enzyme had no effect on the viability of E. coli strains but sensitized strains expressing PSA to killing by the complement system. This study demonstrates the potential therapeutic efficacy of agents that cure infections by modification of the bacterial phenotype rather than by killing or inhibition of growth of the pathogen.

De novo development of presumed cavernomas following resolution of E. Coli subdural empyemas.

Cavernomas fall within the group of angiographically occult lesions and may be found in up to 4 % of the population [1]. They may occur at any age, and with the advent of MRI incidental cavernomas are increasingly identified. The pathogenesis is uncertain. Familial cases are well recognised with a reported prevalence of 10-15 % [2-3]. The incidence of new lesions has been reported at 0.4 lesions per patient per year in cases with familial cavernomas [4]. Presumed cavernomas have been documented following radiation for malignancy [5-6], and stereotactic cerebral biopsy [7]. There have been no previously documented cases of de novo genesis of cavernomas following bacterial meningitis and subdural empyemas.

Enterobacteriaceae meningitis in adults: a review of 20 consecutive cases 1977-97.

Enterobacteriaceae are not a frequent cause of meningitis in adults and are seen mainly in neurosurgical patients and on occasion in elderly and debilitated patients. Consequently, most series studied have been small and selected. In order to obtain a clearer clinical picture, we reviewed 20 consecutive cases of Enterobacteriaceae meningitis admitted to the Department of Infectious Diseases, Rigshospitalet, Copenhagen, during the years 1977-97. They comprised 1.5% of all cases of acute bacterial meningitis admitted to the department. All of the patients were either elderly and/or had 1 or more underlying diseases and predisposing factors. The clinical presentation and cerebrospinal fluid findings were not different from that of acute bacterial meningitis in general. The mortality rate was 40% and correlated with simultaneous bacteraemia. Complications were seen in a further 30% of patients and 25% survived with different sequelae. These high rates may, at least in part, be due to the advanced age and debilitated state of the patients studied. Escherichia coli was the most frequent of the Enterobacteriaceae.