Etiology of Pediatric Meningitis in West Africa Using Molecular Methods in the Era of Conjugate Vaccines against Pneumococcus, Meningococcus, and Haemophilus influenzae Type b.

Despite the implementation of effective conjugate vaccines against the three main bacterial pathogens that cause meningitis, Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis serogroup A, the burden of meningitis in West Africa remains high. The relative importance of other bacterial, viral, and parasitic pathogens in central nervous system infections is poorly characterized. Cerebrospinal fluid (CSF) specimens were collected from children younger than 5 years with suspected meningitis, presenting at pediatric teaching hospitals across West Africa in five countries including Senegal, Ghana, Togo, Nigeria, and Niger. Cerebrospinal fluid specimens were initially tested using bacteriologic culture and a triplex real-time polymerase chain reaction (PCR) assay for N. meningitidis, S. pneumoniae, and H. influenzae used in routine meningitis surveillance. A custom TaqMan Array Card (TAC) assay was later used to detect 35 pathogens including 15 bacteria, 17 viruses, one fungus, and two protozoans. Among 711 CSF specimens tested, the pathogen positivity rates were 2% and 20% by the triplex real-time PCR (three pathogens) and TAC (35 pathogens), respectively. TAC detected 10 bacterial pathogens, eight viral pathogens, and Plasmodium. Overall, Escherichia coli was the most prevalent (4.8%), followed by S. pneumoniae (3.5%) and Plasmodium (3.5%). Multiple pathogens were detected in 4.4% of the specimens. Children with human immunodeficiency virus (HIV) and Plasmodium detected in CSF had high mortality. Among 220 neonates, 17% had at least one pathogen detected, dominated by gram-negative bacteria. The meningitis TAC enhanced the detection of pathogens in children with meningitis and may be useful for case-based meningitis surveillance.

Comparison of CSF and MRI Findings among Neonates and Infants with E coli or Group B Streptococcal Meningitis.

BACKGROUND AND PURPOSE: Group B Streptococcus and Escherichia coli (E coli) are the 2 most common causes of bacterial meningitis in neonates. The purpose of this study was to determine whether CSF and/or MR imaging findings differ between infants with group B streptococcal or E coli meningitis. MATERIALS AND METHODS: A retrospective review was performed among neonates (younger than 28 days) and infants (younger than 120 days) with proved group B streptococcal (n = 57) or E coli meningitis (n = 50). A CSF or blood culture positive for Streptococcus or E coli and an elevated CSF white blood cell count were used as the criterion standard. Independent, blinded review of brain MRIs obtained within 21 days of presentation were performed by 2 board-certified neuroradiologists. CSF laboratory values and MR imaging findings were compared between the groups. RESULTS: There was no statistically significant difference between the mean age at presentation for patients with group B streptococcal (40 days; range, 2-111 days) versus patients with E coli meningitis (31 days; range, 12-115 days) (P = .18). There was no statistically significant difference in the CSF white blood cell count, glucose, or protein. There was a significant difference between group B streptococcal and E coli meningitis in the frequency of hydrocephalus (0% versus 22%, P = .001) and infarct (40% versus 14%; P = .038), respectively. There was no statistically significant difference in leptomeningeal enhancement, cerebritis, ventriculitis, abscess/granuloma, subdural effusion, extra-axial purulent material, intraventricular purulent material, hemorrhage, and sinus thrombosis. CONCLUSIONS: Although neonates and infants with group B streptococcal or E coli meningitis had similar age and CSF laboratory values, patients with group B streptococcal meningitis more frequently demonstrated infarcts, while those with E coli meningitis more frequently had early onset of hydrocephalus.

Community-acquired meningitis in adults caused by Escherichia coli in Denmark and The Netherlands.

OBJECTIVES: We aimed to examine risk factors, presenting characteristics and complications of Escherichia coli community-acquired bacterial meningitis in adults. METHODS: Observational cohort study of adults > 16 years of age with cerebrospinal fluid culture-positive E. coli meningitis in Denmark and the Netherlands. Exclusion criteria were primary brain abscess, previous neurosurgery and nosocomial infections. We analysed baseline characteristics, concomitant infections and neurological complications. Outcome was assessed using the Glasgow Outcome Scale score (GOS) at discharge with GOS 1-4 categorised as unfavourable outcome. RESULTS: We identified 36 patients with a median age of 69 years (interquartile range 61-83) of whom 15 (42%) were females. Immuno-compromise was present in 11 (31%) patients. Nineteen (53%) patients had concomitant infections consisting of urinary tract infections in 13 (36%), pneumonia in three (9%) and septic arthritis in two (6%). Bacteraemia with E. coli was found in 26 of 34 (76%) patients. Thirteen patients died (36%) and unfavourable outcome at discharge occurred in 23 (64%). Deaths were attributed to systemic complications in 12 (92%) patients. CONCLUSION: Community-acquired E. coli meningitis in adults is a severe disease that primarily occurs in elderly patients with concomitant infections and an immunocompromised state. Outcome is often poor and mainly caused by systemic complications.

Excessive external drainage of CSF might aggravate bacterial ventriculitis.

Bacterial ventriculitis is one of the most difficult diseases of neurosurgery, if not controlled well in the early stage, it will cause empyema, adhesion and separated infectious ventricle locules inside the ventricle. Few studies focus on the relationship between external drainage volume and the occurrence of adhesion and separation of the ventricle. This paper reported a case of ventriculitis, and we propose that excessive external drainage might increase the occurrence rate of the internal separation and adhesion of ventricle in patients with ventriculitis. Choosing an appropriate drainage method and avoiding excessive drainage might be the key to the treatment of ventriculitis.

Thalamic involvement in patients with neurologic impairment due to Shiga toxin 2.

OBJECTIVE: The outbreak of hemolytic-uremic syndrome and diarrhea caused by Shiga toxin-producing Escherichia coli O104:H4 in Germany during May to July 2011 involved severe and characteristic neurologic manifestations with a strong female preponderance. Owing to these observations, we designed a series of experimental studies to evaluate the underlying mechanism of action of this clinical picture. METHODS: A magnetic resonance imaging and electroencephalographic study of patients was performed to evaluate the clinical picture in detail. Thereafter, combinations of different experimental settings, including electrophysiological and histological analyses, as well as calcium imaging in brain slices of rats, were conducted. RESULTS: We report on 7 female patients with neurologic symptoms and signs including bilateral thalamic lesions and encephalopathic changes indicative of a predominant involvement of the thalamus. Experimental studies in rats revealed an enhanced expression of the Shiga toxin receptor globotriaosylceramide on thalamic neurons in female rats as compared to other brain regions in the same rats and to male animals. Incubation of brain slices with Shiga toxin 2 evoked a strong membrane depolarization and intracellular calcium accumulation in neurons, associated with neuronal apoptosis, predominantly in the thalamic area. INTERPRETATION: These findings suggest that the direct cytotoxic effect of Shiga toxin 2 in the thalamus might contribute to the pathophysiology of neuronal complications in hemolytic-uremic syndrome.

Multiple therapeutic effects of adjunctive baicalin therapy in experimental bacterial meningitis.

This study aimed to examine effects of adjunctive baicalin therapy to ampicillin for experimental bacterial meningitis in rabbits. After Escherichia Coli inoculation, mean leukocyte counts, concentrations of protein, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and lactate in cerebrospinal fluid (CSF), brain water content and mean arterial and intracranial pressures substantially increased in the meningitis group. Ampicillin alone for 5 h markedly exacerbated the enhanced leukocyte counts and protein concentration, and showed no significant effect on the elevated CSF TNF-alpha, IL-1 and lactate concentration, mean arterial and intracranial pressures, and brain water content. Baicalin (7-D-glucuronic acid-5,6-dihydroxyflavone, C(21)H(18)O(11)) completely counteracted ampicillin-induced exacerbation, and further alleviated the enhanced mean leukocyte counts and protein concentration when combined with ampicillin. Adjunctive baicalin also significantly ameliorated the elevated CSF TNF-alpha, IL-1 and lactate concentration, mean arterial and intracranial pressures, and brain water content. Baicillin, as an adjunctive treatment exerted multiple therapeutic effects in experimental bacterial meningitis.

Prospective study of use of PCR amplification and sequencing of 16S ribosomal DNA from cerebrospinal fluid for diagnosis of bacterial meningitis in a clinical setting.

We have evaluated the use of a broad-range PCR aimed at the 16S rRNA gene in detecting bacterial meningitis in a clinical setting. To achieve a uniform DNA extraction procedure for both gram-positive and gram-negative organisms, a combination of physical disruption (bead beating) and a silica-guanidiniumthiocyanate procedure was used for nucleic acid preparation. To diminish the risk of contamination as much as possible, we chose to amplify almost the entire 16S rRNA gene. The analytical sensitivity of the assay was approximately 1 x 10(2) to 2 x 10(2) CFU/ml of cerebrospinal fluid (CSF) for both gram-negative and gram-positive bacteria. In a prospective study of 227 CSF samples, broad-range PCR proved to be superior to conventional methods in detecting bacterial meningitis when antimicrobial therapy had already started. Overall, our assay showed a sensitivity of 86%, a specificity of 97%, a positive predictive value of 80%, and a negative predictive value of 98% compared to culture. We are currently adapting the standard procedures in our laboratory for detecting bacterial meningitis; broad-range 16S ribosomal DNA PCR detection is indicated when antimicrobial therapy has already started at time of lumbar puncture or when cultures remain negative, although the suspicion of bacterial meningitis remains.

Shock séptico secundario a absceso tiroideo / Septic shock secondary to thyroid abscess

El absceso tiroideo constituye una entidad infrecuente y es poco habitual que sea causa de un proceso séptico que requiera ingreso en la UCI. Son pocos los casos publicados en la bibliografía, en su mayoría relacionados con focos sépticos primarios o, más frecuentemente, con la persistencia del arco branquial, enfermedad tiroidea o en pacientes inmunodeprimidos. Presentamos el caso de una paciente con insuficiencia renal crónica y en programa de diálisis peritoneal ambulatoria sin enfermedad tiroidea previa conocida que comenzó con un cuadro séptico y edematización cervical y que evolucionó a un estado de shock séptico (AU)

Are routine sensitivity test data suitable for the surveillance of resistance? Resistance rates amongst Escherichia coli from blood and CSF from 1991-1997, as assessed by routine and centralized testing.

Surveillance of antibiotic resistance can be undertaken by compilation of routine data or by central testing of isolates. Routine results can be obtained cheaply and in sufficient quantities for correlation with population and prescribing denominators but there is concern about their quality. As one of a series of ongoing studies to assess this quality, we compared the proportions of resistance amongst Escherichia coli from patients with bacteraemia or meningitis between 1991 and 1997 (i) as recorded in routine data reported to the PHLS and (ii) as found in tests performed at the PHLS Laboratory of Enteric Pathogens (LEP). These two data sets both showed an overall upward trend in the proportion of isolates resistant to ampicillin, trimethoprim, gentamicin and ciprofloxacin. The average annual percentage increase in resistance was estimated in separate logistic regression models, and 95% confidence intervals (CI) were determined. The annual percentage increases in the proportions of isolates reported resistant were similar in the two data sets for trimethoprim, gentamicin and ciprofloxacin but differed for ampicillin. The upward trends were statistically significant except for gentamicin resistance in the LEP data set, where the 95% CI straddled zero. The proportions of resistant isolates for each antibiotic in the two data sets each year were in poorer agreement than the trends; however, the 95% CI of the difference of proportions resistant between the routine and LEP data sets straddled zero in 4 or 5 of the 7 years studied. Some discrepancies might be explained by geographical bias in the sampling or by differences in definitions of resistance. Thus (i) the proportion of resistant isolates tested at LEP almost always fell within the ranges bounded by the highest and lowest proportions for individual Regional Health Authorities, as recorded in the routine data, and (ii) the fact that LEP consistently recorded less gentamicin resistance but more ciprofloxacin resistance than the routine could be explained by breakpoint differences. We conclude that routine susceptibility data for ampicillin, ciprofloxacin, gentamicin and trimethoprim appear sound for E. coli and might be suitable for correlation with other data, e.g. for prescribing.

The origin and function of soluble CD14 in experimental bacterial meningitis.

Murine experimental meningitis models induced by either Escherichia coli LPS, live Streptococcus pneumoniae, or Listeria monocytogenes were used to study the origin and potential function of soluble CD14 (sCD14) in the brain during bacterial meningitis. Whereas intracerebral infection caused only a minor and/or transient increase of sCD14 levels in the serum, dramatically elevated concentrations of sCD14 were detected in the cerebrospinal fluid. Reverse-transcriptase PCR and FACS analysis of the leukocytes invading the subarachnoid compartment revealed an active amplification of CD14 transcription and concomitant surface expression. These findings were confirmed by in situ hybridization and immunohistochemical analysis. In contrast, parenchymal astrocytes and microglial cells were shown not to significantly contribute to the elevated levels of sCD14. Simultaneous intracerebral inoculation of rsCD14 and S. pneumoniae resulted in a markedly increased local cytokine response. Taken together, these data provide the first evidence that sCD14 can act as an inflammatory co-ligand in vivo. Thus, during bacterial meningitis, sCD14 is massively released by intrathecal leukocytes, and the sCD14 found in the cerebrospinal fluid can play an important role in the pathogenesis of this disease.

[Escherichia coli meningitis in a 16-month old infant revealing a posterior fossa epidermoid cyst]. / Méningite à Escherichia coli chez un nourrisson de 16 mois révélant un kyste épidermoïde de la fosse postérieure.

UNLABELLED: Meningitis due to Escherichia coli is rare, and generally observed in very particular circumstances, such as neonatal period, anatomical anomalies or in immune-deficient patients. CASE REPORT: A 16-month-old male infant was admitted for acute meningitis. E coli was detected in the cerebro-spinal fluid (CSF). As appropriate antibiotic treatment proved inefficient, a cerebral computerised tomography (CT) scan was performed, revealing an epidermoid cyst of the posterior fossa. The cyst was resected after CSF sterilisation. Postoperative recovery was satisfactory. CONCLUSION: When an unusual bacterial species such as E coli is detected in CSF, the authors suggest consideration of a cutaneous or ETN focus, or a congenital malformation with communication between cutaneous and meningeal structures.

Phylogenetic analysis of Escherichia coli strains causing neonatal meningitis suggests horizontal gene transfer from a predominant pool of highly virulent B2 group strains.

Phylogenetic relationships of 69 neonatal meningitis Escherichia coli strains isolated worldwide were studied. Restriction fragment length polymorphism of rrn operons (rrn RFLP) in these isolates was compared with that of the 72 strains of the ECOR reference collection. Distributions of K1 antigen, of polymerase chain reaction-detected ibe10 gene, pap, afa, sfa/foc, hly, and aer operons, and of a 14.9-kb rrn-containing HindIII fragment previously associated with neonatal meningitis were compared. Oligoclonality was observed for the meningitis strains. Factorial analysis of correspondence on the rrn RFLP data showed a frequency gradient of meningitis strains from the phylogenetic B2 group (68%) to the A group (6%), via the D and B1 groups (26%). The distribution of the virulence determinants argues for their horizontal transfer during the evolution of E. coli. Analysis of the status of some neonates further suggests that neonatal meningitis results from a balance between bacterial genes of virulence and host factors.

Virulence patterns of Escherichia coli K1 strains associated with neonatal meningitis.

The prevalence of the ibe10 gene, of the pap, afa, and sfa adhesin-encoding operons, and of a 14.9-kb rrn-containing HindIII fragment was studied for 67 Escherichia coli neonatal meningitis strains, 58 E. coli K1 commensal strains, and 47 E. coli blood isolates from neonates without meningitis. ibe10, sfa, and the 14.9-kb HindIII fragment were observed significantly more often in the meningitis strains than in blood or commensal strains.

Intracerebral sepsis due to intestinal perforation by ventriculo-peritoneal shunts: two cases.

Two cases of ventriculo-peritoneal (V-P) shunt infection attributable to intestinal perforation are reported. One patient developed a brain abscess, the other ventriculitis. Microbiology consisted of faecal flora and the peritoneal catheter was found to be faecally stained in both cases. There were no abdominal symptoms or signs. It is likely that infection developed via the ascending route.

Evaluation of hematological, serum biochemical and cerebrospinal fluid parameters in experimental bacterial meningitis in the calf.

To evaluate the effects of bacterial meningitis on blood and CSF parameters, an experiment was conducted with five Iranian crossbred male calves. Blood and CSF samples were collected 3 times within a 5-day interval before the administration of bacteria for obtaining control values. Following the injection of E. coli, K12 into the cerebrospinal fluid from the lumbosacral space, samples were collected and clinical signs of meningitis were observed. Blood and CSF samples were obtained from the meningitis group 3 times at 1, 3, and 5 days post injection. The treatment of the infected calves using lincospectin and tetracycline was carried out immediately after the onset of clinical signs. After the treatment, blood and CSF samples were obtained 3 times during a 5-day period. Following the induction of meningitis, the number of WBCs, neutrophils, eosinophils and monocytes significantly increased (P < 0.05). However, the percent of lymphocytes decreased significantly (P < 0.05). The concentrations of glucose, potassium and activity of AST, LDH, CK significantly increased (P < 0.05). In contrast, the concentrations of phosphorous, sodium and magnesium significantly decreased (P < 0.05). Furthermore, following the induction of meningitis, the CSF was slightly xantochromic and turbid. The concentrations of protein, cholesterol, phosphorous, potassium, the activities of AST, LDH, CK, and the cell numbers in the CSF increased significantly (P < 0.05). In contrast, the concentration of glucose and pH in the CSF decreased significantly (P < 0.05). This study showed that bacterial meningitis can have profound effects on blood and CSF parameters which enable one to reach diagnosis.

Antibiotic resistance in Escherichia coli isolated from blood and cerebrospinal fluid: a 6-year study of isolates from patients in England and Wales.

A study of the incidence of resistance to antimicrobial drugs in Escherichia coli from blood and CSF made in England and Wales in the 6-year period 1991 1996 has demonstrated a significant increase in the incidence of strains resistant to ampicillin and ciprofloxacin, two antibiotics used for first-line therapy of invasive disease. In particular, there has been a dramatic change in the occurrence of isolates with low level or high level resistance to ciprofloxacin; over 90% of isolates in the high level group were also resistant to at least four other antimicrobials. Physicians in England and Wales should be aware that there is now an increasing possibility of treatment failures when ciprofloxacin is used for the treatment of invasive E. coli infections.

Genotyping may provide rapid identification of Escherichia coli K1 organisms that cause neonatal meningitis.

Escherichia coli K1 is the most common cause of gram-negative neonatal bacterial meningitis and septicemia. In an attempt to identify genetic markers in E. coli K1 that are associated with the capacity of the organism to cause neonatal meningitis, we used rRNA gene restriction patterns. E. coli strains isolated from the CSF of neonates with meningitis (n = 43) on two continents were compared to strains isolated from the blood of neonates with bacteremia who did not have meningitis (n = 29) and to isolates from the vaginas of asymptomatic pregnant women whose neonates remained without infection (n = 39). E. coli strains from CSF are genetically less heterogeneous than isolates from blood and the vagina: 44.2% of the CSF isolates belonged to only two types, whereas no more than two blood vaginal strains were of the same type. After HindIII digestion, a 14.9-kb rDNA-containing fragment was found in 81.3% of the strains from CSF vs. 28.0% of the isolates from blood and only 12.8% of the vaginal isolates (P = .001). Thus, genotyping might provide markers to identify organisms in the maternal vaginal flora that are highly likely to cause neonatal meningitis. This observation may have very practical implications for the early identification of these organisms in pregnant women and thus for the selective establishment of preventive measures per partum or for the early treatment of colonized neonates.