Clinical significance of Epstein-Barr virus in the cerebrospinal fluid of immunocompetent patients.

INTRODUCTION: Polymerase chain reaction (PCR)-based testing of cerebrospinal fluid (CSF) samples has greatly facilitated the diagnosis of central nervous system (CNS) infections. However, the clinical significance of Epstein-Barr virus (EBV) DNA in CSF of individuals with suspected CNS infection remains unclear. We wanted to gain a better understanding of EBV as an infectious agent in immunocompetent patients with CNS disorders. METHODS: We identified cases of EBV-associated CNS infections and reviewed their clinical and laboratory characteristics. The study population was drawn from patients with EBV PCR positivity in CSF who visited Pusan National University Hospital between 2010 and 2019. RESULTS: Of the 780 CSF samples examined during the 10-year study period, 42 (5.4 %) were positive for EBV DNA; 9 of the patients (21.4 %) were diagnosed with non-CNS infectious diseases, such as optic neuritis, Guillain-Barré syndrome, and idiopathic intracranial hypotension, and the other 33 cases were classified as CNS infections (22 as encephalitis and 11 as meningitis). Intensive care unit admission (13/33 patients, 39.3 %) and presence of severe neurological sequelae at discharge (8/33 patients, 24.2 %) were relatively frequent. In 10 patients (30.3 %), the following pathogens were detected in CSF in addition to EBV: varicella-zoster virus (n = 3), cytomegalovirus (n = 2), herpes simplex virus 1 (n = 1), herpes simplex virus 2 (n = 1), Streptococcus pneumomiae (n = 2), and Enterococcus faecalis (n = 1). The EBV-only group (n = 23) and the co-infection group (n = 10) did not differ in age, gender, laboratory data, results of brain imaging studies, clinical manifestations, or prognosis; however, the co-infected patients had higher CSF protein levels. CONCLUSION: EBV DNA in CSF is occasionally found in the immunocompetent population; the virus was commonly associated with encephalitis and poor prognosis, and frequently found together with other microbes in CSF.

Causes of Pediatric Meningitis in Botswana: Results From a 16-Year National Meningitis Audit.

BACKGROUND: Central nervous system infections are an important cause of childhood morbidity and mortality in high HIV-prevalence settings of Africa. We evaluated the epidemiology of pediatric meningitis in Botswana during the rollout of antiretroviral therapy, pneumococcal conjugate vaccine and Haemophilus influenzae type B (HiB) vaccine. METHODS: We performed a cross-sectional study of children (<15 years old) evaluated for meningitis by cerebrospinal fluid (CSF) examination from 2000 to 2015, with complete national records for 2013-2014. Clinical and laboratory characteristics of microbiologically confirmed and culture-negative meningitis were described and incidence of Streptococcus pneumoniae, H. influenzae and cryptococcal meningitis was estimated for 2013-2014. RESULTS: A total of 6796 unique cases were identified. Median age was 1 year [interquartile range 0-3]; 10.4% (435/4186) of children with available HIV-related records were known HIV-infected. Overall, 30.4% (2067/6796) had abnormal CSF findings (positive microbiologic testing or CSF pleocytosis). Ten percent (651/6796) had a confirmed microbiologic diagnosis; including 26.9% (175/651) Cryptococcus, 18.9% (123/651) S. pneumoniae, 20.3% (132/651) H. influenzae and 1.1% (7/651) Mycobacterium tuberculosis. During 2013-2014, national cryptococcal meningitis incidence was 1.3 cases per 100,000 person-years (95% confidence interval, 0.8-2.1) and pneumococcal meningitis incidence 0.7 per 100,000 person-years (95% confidence interval, 0.3-1.3), with no HiB meningitis diagnosed. CONCLUSIONS: Following HiB vaccination, a marked decline in microbiologically confirmed cases of H. influenzae meningitis occurred. Cryptococcal meningitis remains the most common confirmed etiology, demonstrating gaps in prevention-of-mother-to-child transmission and early HIV diagnosis. The high proportion of abnormal CSF samples with no microbiologic diagnosis highlights limitation in available diagnostics.

Recurrent Streptococcus pneumoniae meningitis and Mondini dysplasia: Association or causation?

Mondini dysplasia is a developmental disorder of the inner ear structures and it is a rare cause of recurrent bacterial meningitis in children. A 10-year-old boy presented with acute febrile encephalopathy and right ear pain. In the past, he had suffered from two distinct episodes of pyogenic meningitis. On examination, he had signs of meningeal irritation and right ear sensorineural deafness. Magnetic resonance imaging of the brain and computerized tomography of the temporal bone was suggestive of Mondini dysplasia in the right ear. Our case highlights the need for (a) screening of hearing loss at the bedside by Rinne and Weber test in case of recurrent bacterial meningitis (b) searching for an underlying inner ear malformation if there is a hearing loss.

Role of purinergic signaling in experimental pneumococcal meningitis.

Excessive neutrophilic inflammation contributes to brain pathology and adverse outcome in pneumococcal meningitis (PM). Recently, we identified the NLRP3 inflammasome/interleukin (IL)-1ß pathway as a key driver of inflammation in PM. A critical membrane receptor for NLRP3 inflammasome activation is the ATP-activated P2 purinoceptor (P2R) P2X7. Thus, we hypothesized involvement of ATP and P2Rs in PM. The functional role of ATP was investigated in a mouse meningitis model using P2R antagonists. Brain expression of P2Rs was assessed by RT-PCR. ATP levels were determined in murine CSF and cell culture experiments. Treatment with the P2R antagonists suramin or brilliant blue G did not have any impact on disease course. This lack of effect might be attributed to meningitis-associated down-regulation of brain P2R expression and/or a drop of cerebrospinal fluid (CSF) ATP, as demonstrated by RT-PCR and ATP analyses. Supplemental cell culture experiments suggest that the reduction in CSF ATP is, at least partly, due to ATP hydrolysis by ectonucleotidases of neutrophils and macrophages. In conclusion, this study suggests that ATP-P2R signaling is only of minor or even no significance in PM. This may be explained by down-regulation of P2R expression and decreased CSF ATP levels.

Leukocyte attraction by CCL20 and its receptor CCR6 in humans and mice with pneumococcal meningitis.

We previously identified CCL20 as an early chemokine in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels were significantly elevated in the CSF of patients with pneumococcal meningitis and correlated with CSF leukocyte counts. CCR6-deficient mice with pneumococcal meningitis and WT mice with pneumococcal meningitis treated with anti-CCL20 antibodies both had reduced CSF white blood cell counts. The reduction in CSF pleocytosis was also accompanied by an increase in brain bacterial titers. Additional in vitro experiments showed direct chemoattractant activity of CCL20 for granulocytes. In summary, our results identify the CCL20-CCR6 axis as an essential component of the innate immune defense against pneumococcal meningitis, controlling granulocyte recruitment.

Matrix metalloproteinase inhibition lowers mortality and brain injury in experimental pneumococcal meningitis.

Pneumococcal meningitis (PM) results in high mortality rates and long-lasting neurological deficits. Hippocampal apoptosis and cortical necrosis are histopathological correlates of neurofunctional sequelae in rodent models and are frequently observed in autopsy studies of patients who die of PM. In experimental PM, inhibition of matrix metalloproteinases (MMPs) and/or tumor necrosis factor (TNF)-converting enzyme (TACE) has been shown to reduce brain injury and the associated impairment of neurocognitive function. However, none of the compounds evaluated in these studies entered clinical development. Here, we evaluated two second-generation MMP and TACE inhibitors with higher selectivity and improved oral availability. Ro 32-3555 (Trocade, cipemastat) preferentially inhibits collagenases (MMP-1, -8, and -13) and gelatinase B (MMP-9), while Ro 32-7315 is an efficient inhibitor of TACE. PM was induced in infant rats by the intracisternal injection of live Streptococcus pneumoniae. Ro 32-3555 and Ro 32-7315 were injected intraperitoneally, starting at 3 h postinfection. Antibiotic (ceftriaxone) therapy was initiated at 18 h postinfection, and clinical parameters (weight, clinical score, mortality rate) were recorded. Myeloperoxidase activities, concentrations of cytokines and chemokines, concentrations of MMP-2 and MMP-9, and collagen concentrations were measured in the cerebrospinal fluid. Animals were sacrificed at 42 h postinfection, and their brains were assessed by histomorphometry for hippocampal apoptosis and cortical necrosis. Both compounds, while exhibiting disparate MMP and TACE inhibitory profiles, decreased hippocampal apoptosis and cortical injury. Ro 32-3555 reduced mortality rates and cerebrospinal fluid TNF, interleukin-1ß (IL-1ß) and collagen levels, while Ro 32-7315 reduced weight loss and cerebrospinal fluid TNF and IL-6 levels.

Cerebrospinal-fluid cytokine and chemokine profile in patients with pneumococcal and meningococcal meningitis.

BACKGROUND: Bacterial meningitis is characterized by an intense inflammatory reaction contributing to neuronal damage. The aim of this study was to obtain a comparative analysis of cytokines and chemokines in patients with pneumococcal (PM) and meningococcal meningitis (MM) considering that a clear difference between the immune response induced by these pathogens remains unclear. METHODS: The cyto/chemokines, IL-1ß, IL-2, IL-6, TNF-α, IFN-γ, IL-10, IL-1Ra, CXCL8/IL-8, CCL2/MCP-1, CLL3/MIP-1α, CCL4/MIP-1γ and G-CSF, were measured in cerebrospinal fluid (CSF) samples from patients with PM and MM. Additionally, a literature review about the expression of cytokines in CSF samples of patients with MB was made. RESULTS: Concerning cytokines levels, only IFN-γ was significantly higher in patients with Streptococcus pneumoniae compared to those with Neisseria meningitidis, regardless of the time when the lumbar puncture (LP) was made. Furthermore, when samples were compared considering the timing of the LP, higher levels of TNF-α (P <0.05) were observed in MM patients whose LP was made within 48 h from the initial symptoms of disease. We also observed that the index of release of cyto/chemokines per cell was significantly higher in PM. From the literature review, it was observed that TNF-α, IL-1ß and IL-6 are the best studied cytokines, while reports describing the concentration of the cytokine IL-2, IL-1Ra, G-CSF and CCL4/MIP-1ß in CSF samples of patients with bacterial meningitis were not found. CONCLUSION: The data obtained in this study and the previously published data show a similar profile of cytokine expression during PM and MM. Nevertheless, the high levels of IFN-γ and the ability to release high levels of cytokines with a low number of cells are important factors to be considered in the pathogenesis of PM and thereby should be further investigated. Moreover, differences in the early response induced by the pathogens were observed. However, the differences observed are not sufficient to trigger changes in the current therapy of corticosteroids adopted in both the PM and MM.

[A case report of Streptococcus pneumoniae-induced hemolytic uremic syndrome: appropriate transfusional management by T-antigen determination]. / Un cas de syndrome hémolytique et urémique à Streptococcus pneumoniae : prise en charge transfusionnelle adaptée par la recherche de l'antigène T.

Pediatric hemolytic uremic syndrome (HUS) is a rare complication of infections usually caused by Escherichia coli; Streptococcus pneumoniae may be a causative agent in 5% of cases and is often more serious in terms of morbidity and mortality. We report a case of pediatric HUS following an infection by a serotype of S. pneumoniae not included in the vaccine administered to the child. Bacterial neuraminidase revealed a T-antigen and a Tk-antigen and red blood cells polyagglutinability in the laboratory test. Transfusion has been reoriented by an indication of secondary preparations: deplasmatisation of red blood cells and platelets and abstention of therapeutic plasma administration. HUS evolved favorably in a few days but the child retains consequences of meningitis cerebral anoxia.

Bacterial meningitis secondary to stapes footplate malformation in a child with an auditory brainstem implant.

OBJECTIVE: We report a rare presentation of otogenic bacterial meningitis secondary to a stapes footplate malformation in a paediatric patient with an auditory brainstem implant. CASE REPORT: A patient with Mondini's dysplasia developed meningitis six years after auditory brainstem implantation. The aetiology was believed to be otogenic, secondary to stapes footplate malformation. CONCLUSION: To our best knowledge, this is the first report of otogenic bacterial meningitis secondary to stapes footplate malformation in a paediatric patient with an auditory brainstem implant. Subjects with inner ear malformations, especially Mondini's dysplasia, need to be carefully evaluated pre-operatively to reduce or eliminate any anatomical conditions which may predispose to meningitis. In children with an auditory brainstem implant and suspected ear malformation, we recommend pre-operative radiological investigation to look for the 'bulging oval window' sign. When radiological signs are positive, bilateral exploratory tympanotomy should be performed to detect any undiagnosed anatomical stapes footplate defects, which may predispose to bacterial meningitis.

Acute meningitis prognosis using cerebrospinal fluid interleukin-6 levels.

BACKGROUND: Improved diagnostic tests would aid in diagnosing and treating community-acquired meningitis. OBJECTIVE: To analyze the diagnostic value of interleukin-6 (IL-6) in the cerebrospinal fluid (CSF) of patients presenting with symptoms of acute meningitis. MATERIAL AND METHODS: In a 6-month prospective, observational, cross-sectional emergency department (ED) study, serum and CSF samples were obtained from all patients with a headache and fever in whom the physician suspected meningitis. Patients were excluded if computed tomography findings contraindicated a lumbar puncture, if they had bleeding disorders, or if their serum indicated bleeding. IL-6 levels were measured and compared in patients with (Group A) and without (Group B) bacterial meningitis. RESULTS: Samples were obtained from 53 patients, of whom 40 were ultimately found to have meningitis. These 40 patients averaged 49.6 ± 21.9 years, with number of men 18 (45%), hospitalizations 21 (52%), mortality 3 (.07%), and IL-6 average rating 491 (median: 14.5; range 0000-6000). Findings in the two groups were: Group A (with meningitis): n = 13, average IL-6 level: 1495 (median: 604; 25/75 percentiles: 232.5-2030; 95% confidence interval [CI] 371.7-2618.6; range 64-6000). Group B (with aseptic meningitis): n = 27, average IL-6 level: 7.34 (median: 5; 25/75 percentiles: 0.0/15.1; 95% CI 3.94-10.73; range 0-23.6). Mann-Whitney rank sum test: p < 0.0001. CONCLUSIONS: In patients with acute bacterial meningitis, CSF cytokine concentrations are elevated. Measuring CSF inflammatory cytokine levels in patients with acute meningitis could be a valuable ED diagnostic tool. Using this tool could improve the prognosis of patients with bacterial meningitis by allowing more rapid initiation of antibiotic treatment.

Otogenic pneumococcal meningitis with pneumocephalus.

Streptococcus pneumoniae accounts for approximately 50% of bacterial meningitis cases in the United States annually. Since the advent of antibiotics, pneumococcal meningitis as a complication of a primary otogenic focus has been rare in the United States. The widespread use of immunosuppressants and increasing bacterial resistance to commonly prescribed antibiotics may contribute to a higher incidence of complications of otitis media in the future, similar to that of the pre-antibiotic era. We report a case of otogenic pneumococcal meningitis with pneumocephalus in an adult male on chronic immunosuppressant therapy. A 33-year-old man with Crohn's disease and azathioprine use presented to our Emergency Department with progressive headache while taking antibiotics for otitis media. Initial computed tomography scan of the brain revealed pneumocephaly, and cerebrospinal fluid analysis and culture diagnosed pneumococcal meningitis. The patient continued to have fevers while receiving intravenous antibiotics and underwent bilateral myringotomies; his clinical course subsequently improved significantly. Meningitis is a rare complication of Streptococcus pneumoniae infections since the advent of antibiotics; however, it may become more frequent with increasing antibiotic resistance and a growing population of immunocompromised patients. Additionally, pneumocephalus in the setting of meningitis and otitis media should raise the suspicion for mastoiditis (even without overt clinical findings) and early consultation with an otolaryngologist is warranted.

Tumor necrosis factor alpha (TNF-alpha) levels in the brain and cerebrospinal fluid after meningitis induced by Streptococcus pneumoniae.

Bacterial meningitis due to Streptococcus pneumoniae is associated with a significant mortality rate and persisting neurologic sequelae including sensory-motor deficits, seizures, and impairments of learning and memory. The presence of proliferating bacteria within the subarachnoid and ventricular space compartments triggers an intense inflammatory host response at killing the invading microorganism. Proinflammatory mediators released in the process include tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-6. TNF-alpha have several effects, including cytotoxicity, antiviral activity, transcription factor activation, and immune response regulation. Thus, the aim of this study was to verify the levels of the TNF-alpha after pneumococcal meningitis in male Wistar rats. The animals underwent a magna cistern tap receiving either 10 microL sterile saline as a placebo or an equivalent volume of a S. pneumoniae suspension at the concentration 5 x 10(9)cfu/mL. The animals were killed at 0, 6, 12, 24, 48 and 96 h after induction. The brain was removed and hippocampus, cortex, prefrontal and cerebrospinal fluid (CSF) were isolated and used for the determination of TNF-alpha levels. We found an increase in TNF-alpha levels at 6h after induction of the meningitis in the hippocampus (p<0.01), frontal cortex (p<0.05), and cerebrospinal fluid (p<0.001).There was no alteration in the cortex. Our data suggest that TNF-alpha is involved in the pathophysiology of the pneumococcal meningitis and could be investigated as a putative biomarker for brain damage in the first hours.

High cerebrospinal fluid (CSF) penetration and potent bactericidal activity in CSF of NZ2114, a novel plectasin variant, during experimental pneumococcal meningitis.

Plectasin is the first defensin-type antimicrobial peptide isolated from a fungus and has potent activity against gram-positive bacteria. By using an experimental meningitis model, the penetration of plectasin into the cerebrospinal fluid (CSF) of infected and uninfected rabbits and the bactericidal activities in CSF of the plectasin variant NZ2114 and ceftriaxone against a penicillin-resistant Streptococcus pneumoniae strain (NZ2114 and ceftriaxone MICs, 0.25 and 0.5 microg/ml, respectively) were studied. Pharmacokinetic analysis showed that there was a significantly higher level of CSF penetration of NZ2114 through inflamed than through noninflamed meninges (area under the concentration-time curve for CSF/area under the concentration-time curve for serum, 33% and 1.1%, respectively; P = 0.03). The peak concentrations of NZ2114 in purulent CSF were observed approximately 3 h after the infusion of an intravenous bolus of either 20 or 40 mg/kg of body weight and exceeded the MIC >10-fold for a 6-h study period. Treatment with NZ2114 (40 and 20 mg/kg at 0 and 5 h, respectively; n = 11) caused a significantly higher reduction in CSF bacterial concentrations than therapy with ceftriaxone (125 mg/kg at 0 h; n = 7) at 3 h (median changes, 3.7 log(10) CFU/ml [interquartile range, 2.5 to 4.6 log(10) CFU/ml] and 2.1 log(10) CFU/ml [interquartile range, 1.7 to 2.6 log(10) CFU/ml], respectively; P = 0.001), 5 h (median changes, 5.2 log(10) CFU/ml [interquartile range, 3.6 to 6.1 log(10) CFU/ml] and 3.1 log(10) CFU/ml [interquartile range, 2.6 to 3.7 log(10) CFU/ml], respectively; P = 0.01), and 10 h (median changes, 5.6 log(10) CFU/ml [interquartile range, 5.2 to 5.9 log(10) CFU/ml] and 4.2 log(10) CFU/ml [interquartile range, 3.6 to 5.0 log(10) CFU/ml], respectively; P = 0.03) after the start of therapy as well compared to the CSF bacterial concentrations in untreated rabbits with meningitis (n = 7, P < 0.05). Also, significantly more rabbits had sterile CSF at 5 and 10 h when they were treated with NZ2114 than when they were treated with ceftriaxone (67% [six of nine rabbits] and 0% [zero of seven rabbits], respectively, at 5 h and 75% [six of eight rabbits] and 14% [one of seven rabbits], respectively, at 10 h; P < 0.05). Due to its excellent CSF penetration and potent bactericidal activity in CSF, the plectasin variant NZ2114 could be a promising new option for the treatment of CNS infections caused by gram-positive bacteria, including penicillin-resistant pneumococcal meningitis.

Simple febrile seizures: are the AAP guidelines regarding lumbar puncture being followed?

BACKGROUND: In 1996, the American Academy of Pediatrics (AAP) published a practice parameter recommending that lumbar puncture (LP) be strongly considered in infants younger than 12 months presenting with a first febrile seizure. OBJECTIVE: We sought: (1) to determine if the recommendations of the AAP are being followed by pediatric emergency medicine-trained physicians at our institution; (2) to describe the rate of meningitis among patients with febrile seizure who underwent LP; and (3) to determine if there were differences in performance of LP if children were younger or pretreated with antibiotics. METHODS: A retrospective chart review of patients aged 6 to 12 months presenting with first simple febrile seizure to the emergency department (ED) at Miami Children's Hospital was conducted between January 2001 and November 2005. RESULTS: A total of 242 ED records with a discharge diagnosis including the term "febrile seizure," "seizure," or "meningitis" were identified. Of those, 56 met inclusion criteria for first simple febrile seizure. Lumbar puncture was performed in 28 patients (50%) that met inclusion criteria. Younger patients were no more likely to have LP performed than older patients (P = 0.15). Ten children (17.8%) received antibiotics before the ED visit; of these, 4 (40%) underwent LP in the ED. Children who presented with first simple febrile seizure to our institution who were pretreated with antibiotics were no more likely to have LP performed than those who were not receiving antibiotics (P = 0.48). All cerebrospinal fluid cultures were sterile. CONCLUSION: The AAP recommendations regarding LP in patients 6 to 12 months of age with first simple febrile seizure are not being strictly adhered to. The AAP recommendations regarding simple febrile seizures were conceived in a different epidemiologic era of disease pathology with data not representative of current prevalence and etiologic issues and need to be revisited.

Effects of Toll-like receptor 2 agonist Pam(3)CysSK(4) on inflammation and brain damage in experimental pneumococcal meningitis.

TLR2 signaling participates in the pathogenesis of pneumococcal meningitis. In infant rats, the TLR2 agonist Pam(3)CysSK(4) was applied intracisternally (0.5 microg in 10 microl saline) alone or after induction of pneumococcal meningitis to investigate the effect of TLR2 activation on cerebrospinal fluid (CSF) inflammation and hippocampal apoptosis. A dose effect of Pam(3)CysSK(4) on apoptosis was investigated by intracisternal application of 0.5 microg in 10 microl saline and 40 microg in 20 microl saline. Pam(3)CysSK(4) neither induced apoptosis in sham-operated mice nor aggravated apoptosis in acute infection. However, Pam(3)CysSK(4) induced pleocytosis, TNF-alpha and MMP-9 in CSF in sham-infection but not during acute meningitis. We conclude that TLR2 signaling triggered by Pam(3)CysSK(4) at a dosage capable to induce a neuroinflammatory response does not induce hippocampal apoptosis in the infant rat model of experimental pneumococcal meningitis.

Role of glial cells in the functional expression of LL-37/rat cathelin-related antimicrobial peptide in meningitis.

Antimicrobial peptides are intrinsic to the innate immune system in many organ systems, but little is known about their expression in the central nervous system. We examined cerebrospinal fluid (CSF) and serum from patients with active bacterial meningitis to assess antimicrobial peptides and possible bactericidal properties of the CSF. We found antimicrobial peptides (human cathelicidin LL-37) in the CSF of patients with bacterial meningitis but not in control CSF. We next characterized the expression, secretion, and bactericidal properties of rat cathelin-related antimicrobial peptide, the homologue of the human LL-37, in rat astrocytes and microglia after incubation with different bacterial components. Using real-time polymerase chain reaction and Western blotting, we determined that supernatants from both astrocytes and microglia incubated with bacterial component supernatants had antimicrobial activity. The expression of rat cathelin-related antimicrobial peptide in rat glial cells involved different signal transduction pathways and was induced by the inflammatory cytokines interleukin 1beta and tumor necrosis factor. In an experimental model of meningitis, infant rats were intracisternally infected with Streptococcus pneumoniae, and rat cathelin-related antimicrobial peptide was localized in glia, choroid plexus, and ependymal cells by immunohistochemistry. Together, these results suggest that cathelicidins produced by glia and other cells play an important part in the innate immune response against pathogens in central nervous system bacterial infections.

Acute bacterial meningitis caused by Streptococcus pneumoniae resistant to the antimicrobian agents and their serotypes / Meningite bacteriana aguda por Streptococcus pneumoniae resistente aos antimicrobianos e seus sorotipos

The main objectives of this study are to evaluate the resistance rates of Streptococcus pneumonia to penicillin G, ceftriaxone and vancomycin in patients with meningitis; to analyze possible risk factors to the antimicrobian resistance; to describe the serotypes detected and to suggest an initial empirical treatment for meningitis. The sensitiveness and serotypes of all isolated S. pneumoniae of patients with acute bacterial meningitis received by the Paraná State Central Laboratory from April 2001 to august 2002 have been evaluated. One hundred S. pneumoniae have been isolated, of which 15 percent were resistant to penicillin, 1 percent to cephalosporin and 0 percent to vancomycin. The serotypes most found were 14 (19 percent), 3 and 23F (10 percent each). When only the resistant serotypes were analyzed, the most prevalent was the 14 with 44 percent. The risk factors found in relation to the S. pneumoniae resistance were: age under one year old (p=0.01) and previous use of antibiotic (p=0.046). The resistance rates found, which were moderate to penicillin, low to cephalosporin and neutral to vancomycin, suggest the isolated use of a 3rd generation cephalosporin as an initial empirical therapy for the treatment of acute bacterial meningitis with a communitarian background.

Este estudo teve como objetivo avaliar as taxas de resistência de Streptococcus pneumoniae, isolados de pacientes com meningite, à penicilina G, ceftriaxona e vancomicina; avaliar possíveis fatores de risco para resistência antimicrobiana; descrever os sorotipos encontrados e sugerir a terapêutica empírica inicial para meningite. Foram isoladas 100 amostras de S. pneumoniae, encontrando-se 15 por cento de resistência à penicilina, 1 por cento à cefalosporina e 0 por cento à vancomicina. Os sorotipos mais encontrados foram 14 (19 por cento), 3 e 23F (10 por cento cada). Analisando-se os resistentes, o sorotipo 14 (44 por cento) também foi o mais freqüente. Os fatores de risco para resistência de S. pneumoniae encontrados foram: idade menor que um ano (p=0,01) e o uso prévio de antibiótico (p=0,046). As taxas de resistência encontradas, moderada a penicilina, baixa para cefalosporina e nula para vancomicina, sugerem como terapêutica empírica inicial para tratamento da meningite bacteriana aguda de origem comunitária, a cefalosporina de terceira geração isoladamente.

Increased expression of tyrosine phosphatase SHP2 in experimental pneumococcal meningitis: correlation with tumor necrosis factor-alpha and cerebrospinal fluid pleocytosis.

Protein tyrosine phosphatase SHP2 plays a crucial role in the development of the central nervous system. To explore the expression and possible role of SHP2 during the course of bacterial meningitis, this article reports a juvenile rat bacterial meningitis model established by direct intracisternal injection of Streptococcus pneumoniae. Expression of SHP2 at both mRNA and protein levels were assessed. White blood cell count and concentration of tumor necrosis factor-alpha (TNF-alpha) in cerebrospinal fluid (CSF) were also measured. In the cortex, bacterial meningitis led to a significant upregulation of mRNA encoding SHP2. SHP2 protein levels and CSF white blood cell count were positively correlated. However, there was no significant correlation between the levels of SHP2 protein and TNF-alpha concentrations in CSF. These findings do not support an essential role of SHP2 in the pathogenesis of experimental pneumoniae meningitis, but it is possible that SHP2 protein expression may be used as a marker of disease activity.