Community-acquired Bacterial Meningitis Research Articles

Hospital-Based Study of the Prognostic Factors in Adult Patients with Acute Community-Acquired Bacterial Meningitis in Tokyo, Japan

Prognostic factors related to community-acquired bacterial meningitis (BM) in adult patients have been evaluated using multivariate analysis in The Netherlands, where the rate of antibiotic resistance was low. However, an evaluation of these factors in countries with a high rate of antibiotic resistance has not yet been done. Thus, we studied the prognostic factors in adults with community-acquired BM in our hospitals, which are located in Tokyo, Japan, where the rate of antibiotic resistance is high. We selected 71 consecutive adult patients with community-acquired BM in which the pathogens were identified and then classified the patients into two groups based on the Glasgow Outcome Scale: a favorable outcome group (n=48), and an unfavorable outcome group (n=23). Their clinical and laboratory variables were analyzed using single logistic regression analysis followed by multiple logistic regression analysis. The overall mortality rate was 23%. The rate of antibiotic resistance was 54.9%. The most common resistant bacteria were penicillin-resistant Streptococcus pneumoniae, followed by methicillin-resistant Staphylococcus aureus. The Glasgow Coma Scale score (GCS) at the initiation of antibiotic therapy and a low thrombocyte count were identified as significant unfavorable prognostic factors (GCS: p=0.020, odds ratio=0.528, 95%CI=0.309-0.902; thrombocyte count: p=0.037, odds ratio=0.802, 95%CI=0.652-0.987). The presence of antibiotic-resistant bacteria was not identified as a prognostic factor. Patients with a low GCS at the initiation of antibiotic therapy and low thrombocyte counts had unfavorable outcomes. With appropriate antibiotic administration, the antibiotic-resistant bacteria were not identified as an unfavorable prognostic factor, even in an area with a high rate of antibiotic resistance.

Estudio comparativo de las meningitis por Staphylococcus aureus y Staphylococci coagulasa negativo en adultos

Staphylococcus spp. rarely cause community-acquired acute bacterial meningitis (ABM), but they are a frequent cause of nosocomial meningitis. AIMS. We describe and conduct a comparative analysis of ABM due to S. aureus and coagulase-negative (CoN) Staphylococci in adults. We reviewed the medical records of patients aged 14 or over who had been diagnosed with ABM, including those with a positive cerebrospinal fluid (CSF) culture for Staphylococcus spp. Forty cases were included (28% of the ABM), 12 due to S. aureus and 28 due to CoN Staphylococci. Incidence increased over time: 1.9% in the first third of the study, 22.9% in the second and 19.4% in the third (p = 0.003). In 67% of cases it was nosocomial and post-operative in 95%. Neurosurgical devices (74%) and recent neurosurgery (26%) were the risk factors, and both associated 61%. Clinical signs and symptoms and alterations to CSF were similar in both groups, but bacteraemia (60% versus 20%) and the development of complications were more frequent in infections due to S. aureus. Overall mortality rate was above 15%, and was higher in infections due to S. aureus (67% versus 0%). Mortality was also associated with spontaneous acquisition of the infection (25% versus 0%), the development of septic complications (37% versus 6%), bacteraemia (62% versus 19%) and not withdrawing or changing the neurosurgical device (60% versus 0%). Staphylococcus spp. are a frequent cause of ABM in hospitals with neurosurgery, especially in the post-operative period following neurosurgical procedures and/or in carriers of CSF drainage devices. Prognosis in infections caused by CoN Staphylococci is favourable, in contrast to the high mortality rate caused by S. aureus.

Seizures in Adults with Bacterial Meningitis: Zoons E, Weisfelt M, de Gans J, et al. Neurology 2008:70;2109–15

This retrospective study from the Netherlands sought to determine the occurrence and prognostic significance of seizures in adult bacterial meningitis. Between October 1998 and April 2002, all adults aged > 16 years with community-acquired bacterial meningitis confirmed with cerebrospinal fluid (CSF) culture were prospectively evaluated and data were entered into the Dutch Meningitis Cohort Study database. Main outcome measures were death within 14 days after hospital admission, and seizure occurrence.

CORRIGENDUM

European Journal of NeurologyVolume 15, Issue 8 p. 880-880 Free Access CORRIGENDUM This article corrects the following: EFNS guideline on the management of community-acquired bacterial meningitis: report of an EFNS Task Force on acute bacterial meningitis in older children and adults A. Chaudhuri, P. M. Martin, P. G. E. Kennedy, R. Andrew Seaton, P. Portegies, M. Bojar, I. Steiner, , Volume 15Issue 7European Journal of Neurology pages: 649-659 First Published online: June 10, 2008 First published: 09 July 2008 https://doi.org/10.1111/j.1468-1331.2008.02240.xAboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat In the EFNS Guideline paper [1], in the July issue of European Journal of Neurology, the second author was listed incorrectly as P. M. Martin. The correct name is P. Martinez-Martin. Reference 1 Chaudhuri A, Martin PM, Kennedy PGE, et al. EFNS guideline on the management of community-acquired bacterial meningitis: report of an EFNS Task Force on acute bacterial meningitis in older children and adults. European Journal of Neurology 2008; 15: 649– 659. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar Volume15, Issue8August 2008Pages 880-880 ReferencesRelatedInformation

Clinical Features, Outcome, and Meningococcal Genotype in 258 Adults With Meningococcal Meningitis

Meningococcal meningitis remains a life-threatening disease. Neisseria meningitidis is the leading cause of meningitis and septicemia in young adults and is a major cause of endemic bacterial meningitis worldwide. The Meningitis Cohort Study was a Dutch nationwide prospective observational cohort study of adults with community-acquired bacterial meningitis, confirmed by culture of cerebrospinal fluid, from October 1998 to April 2002. Patients underwent a neurologic examination at discharge, and outcome was graded with the Glasgow Outcome Scale. Serogrouping, multi-locus sequence typing, and susceptibility testing of meningococcal isolates were performed. The study identified 258 episodes of meningococcal meningitis in 258 patients. The prevalence of the classical triad of fever, neck stiffness, and change in mental status was low (70/258, 27%). When rash was added to the classical triad, 229 of 258 (89%) patients had at least 2 of 4 signs. Systolic hypotension was associated with rash (22/23 vs. 137/222, p = 0.002) and absence of neck stiffness (6/23 vs. 21/220, p = 0.05). Neuroimaging before lumbar puncture was an important cause of delay of therapy: antibiotics were not initiated before computed tomography (CT) scan in 85% of patients who underwent CT scan before lumbar puncture. Unfavorable outcome occurred in 30 of 258 (12%) patients, including a mortality rate of 7%. Neurologic sequelae occurred in 28 of 238 (12%) patients, particularly hearing loss (8%). Factors associated with sepsis and infection with meningococci of clonal complex 11 (cc11) are related with unfavorable outcome.

Oral doxycycline for neuroborreliosis

Community-acquired bacterial meningitis (eg, pneumococcal meningitis) and other serious CNS infections are life-threatening and rapidly progressive, and curing them is dependent on achieving bactericidal concentrations of antibiotics at the sites of infection. The general reluctance to treat such infections with oral antibiotics has several causes, such as unreliable drug absorption from the gastrointestinal tract (due to nausea and vomiting or haemodynamic instability), the fact that blood and CSF drug concentrations achievable with many oral agents are much lower than those possible with parenteral antibiotic preparations, and the scarcity of clinical experience with oral antimicrobials for these indications. Consistent with this approach, parenteral antibiotic therapy has commonly been used to treat neuroborreliosis. 1 Steere AC Pachner AR Malawista SE Neurologic abnormalities of Lyme disease: successful treatment with high-dose intravenous penicillin. Ann Intern Med. 1983; 99: 767-772 Google Scholar , 2 Dattwyler RJ Halperin JJ Volkman DJ Luft BJ Treatment of late Lyme borreliosis—randomized comparison of ceftriaxone and penicillin. Lancet. 1988; 1: 1191-1194 Scopus (0) Google Scholar Oral doxycycline versus intravenous ceftriaxone for European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blind, randomised trialOral doxycycline is as efficient as intravenous ceftriaxone for the treatment of European adults with Lyme neuroborreliosis. Full-Text PDF

Seizures in adults with bacterial meningitis

To evaluate the occurrence and prognostic relevance of seizures in adults with community-acquired bacterial meningitis. An observational cross-sectional study, in which patients with seizures are selected from a prospective nationwide cohort of 696 episodes of community-acquired bacterial meningitis, confirmed by culture of CSF in patients aged >16 years. We retrospectively collected data on EEGs. Seizures occurred in 121 of 696 episodes (17%). Death occurred in 41% of patients with seizures compared to 16% of patients without seizures (p < 0.001). The median number of seizures was 2 (interquartile range [IQR] 1 to 4). The median time between admission and the first seizure was 1 day (IQR 0 to 3). Patients with in-hospital seizures were more likely to have a CSF leukocyte count below 1,000 cells/mm(3) (36% vs 25%; p = 0.01), had higher median CSF protein levels (4.8 g/L [IQR 3.4 to 7.6] vs 4.1 g/L [IQR 2.1 to 6.8]), and higher median erythrocyte sedimentation rate (46 mm/hour [IQR 31 to 72] vs 36 mm/hour [IQR 18 to 69]; p = 0.02) than patients without in-hospital seizures. Focal cerebral abnormalities developed more often in patients with in-hospital seizures than in those without (41% vs 14%; p < 0.001). In a multivariate analysis, seizures were significantly more likely in patients with predisposing conditions, tachycardia, a low Glasgow Coma Scale score on admission, infection with Streptococcus pneumoniae, and focal cerebral abnormalities. Neuroimaging was performed on admission in 70% of episodes with prehospital seizures, with CT revealing a focal lesion in 32% of those episodes. Antiepileptic drugs were administered in 82% of patients with seizures and EEG was performed in 31% of episodes; a status epilepticus was recorded in five patients. Seizures occur frequently in adults with community-acquired bacterial meningitis. Seizures are associated with severe CNS and systemic inflammation, structural CNS lesions, pneumococcal meningitis, and predisposing conditions. The high associated mortality rate warrants a low threshold for starting anticonvulsant therapy in those with clinical suspicion of a seizure.

The value of serial cerebrospinal fluid 14-3-3 protein levels in adult community-acquired bacterial meningitis

Increased levels of cerebrospinal fluid (CSF) 14-3-3 proteins have been reported in acute bacterial meningitis. We tested the hypothesis that CSF 14-3-3 protein levels are substantially increased in acute bacterial meningitis and decreased after anti-microbial therapy, and that CSF 14-3-3 protein levels can predict treatment outcomes. We examined serial pan-CSF 14-3-3 (14-3-3-P) protein and five major isoform (beta, gamma, epsilon, eta, zeta) levels in 29 adult community-acquired bacterial meningitis (ACABM) patients. The CSF 14-3-3 protein levels were also evaluated in 12 aseptic meningitis patients during the study period. All of the meningitis patients had a positive result on admission. Levels of CSF 14-3-3 protein in ACABM cases were significantly increased initially, and substantially decreased thereafter. Most of those who survived (survivors = 25 and non-survivors = 4) had nearly cleared their 14-3-3 protein from the CSF before discharge. Conversely, patients who died never cleared their CSF 14-3-3 protein. The median value of CSF 14-3-3-P and 14-3-3 gamma, 14-3-3 eta and 14-3-3 epsilon isoforms on admission in the bacterial meningitis group were 173.7, 137.7, 42.2 and 9.1, respectively, which were statistically significant than those of the aseptic meningitis group (48.4, 39.6, 2.5 and 0, respectively). Stepwise logistic regression analysis showed only CSF 14-3-3 gamma isoform on admission was independently associated with outcome (P = 0.05, OR = 0.991). Serial 14-3-3 protein gamma isoform actually meets the major requirements for outcome prediction in the treatment of ACABM patients. Assay of the 14-3-3 protein gamma isoform should be added as a neuro-pathologic marker among the panel of conventional CSF parameters.

Community-acquired bacterial meningitis in adults

Despite the availability of effective antibiotics, vaccination programmes and skilled acute-care facilities, there is still a significant mortality and morbidity from bacterial meningitis. Neurologists are often called on to “rule...

Community-acquired bacterial meningitis in cirrhotic patients

The Hospital Universitari de Bellvitge (Barcelona, Spain) records all cases of bacterial meningitis in a 120-variable database. The characteristics of bacterial meningitis in cirrhotic patients are not well-known, and all cases of community-acquired bacterial meningitis occurring in cirrhotic patients were therefore identified. During 1977-2002, there were 602 episodes of community-acquired bacterial meningitis in adults, of which 29 (4.8%) occurred in cirrhotic patients. Compared to non-cirrhotic patients, there were significant differences in: duration of disease for >4 days at the time of diagnosis; absence of nuchal rigidity; certain aetiologies, e.g., Escherichia coli and Listeria monocytogenes; renal and liver function impairment; relapse of fever; and incidence of relapse and mortality. Overall, bacterial meningitis in cirrhotic patients was associated with a high mortality rate and a large number of complications. A high index of suspicion is necessary because of the frequent absence of meningeal signs. In addition to the classic meningeal pathogens, other aetiologies, including E. coli and L. monocytogenes, should be considered when prescribing empirical therapy.

Dexamethasone for adult bacterial meningitis

Introduction: Mortality and morbidity from adult community-acquired bacterial meningitis remain quite high despite the use of appropriate antibiotics [1]. Experimental studies in animals have demonstrated that bacterial lysis–induced inflammation contributes to the poor outcome and that adjunctive treatment with dexamethasone reduces inflammation and sequelae [2]. In children, adjunctive dexamethasone therapy given before or with antibiotics has a beneficial effect on severe hearing loss caused by Haemophilus influenzae type 6 meningitis and may have a protective effect in those with pneumococcal meningitis [3]. In addition, adjunctive dexamethasone therapy has been shown to be beneficial for the outcome of adults with tuberculous (TB) meningitis [4]. Prior to the present study that is reviewed here, the paucity of data precluded a recommendation for the routine use of adjunctive dexamethasone therapy in adult bacterial meningitis.

Comparison of broad-range bacterial PCR and culture of cerebrospinal fluid for diagnosis of community-acquired bacterial meningitis

Appropriate, rapid and reliable laboratory tests are essential for the diagnosis and optimal antibiotic therapy of acute bacterial meningitis. Broad-range bacterial PCR, combined with DNA sequencing, was compared with culture-based methods for examining cerebrospinal fluid (CSF) samples from patients with suspected meningitis. In total, 345 CSF specimens from 345 patients were analysed, with acute community-aquired bacterial meningitis being diagnosed in 74 patients. The CSF of 25 patients was positive by both PCR and culture; 26 patients had CSF specimens positive by PCR only, and 14 patients had specimens positive by culture only. The sensitivity of PCR and culture for clinically relevant meningitis was 59% (44 / 74) and 43% (32 / 74), respectively, while the specificity was 97% (264 / 271) and 97% (264 / 271), respectively. The commonest bacterial rRNA gene sequences detected by PCR only were those of Streptococcus pneumoniae and Neisseria meningitidis (n = 12). PCR failed to detect the bacterial rRNA gene in seven specimens from patients with symptoms compatible with acute bacterial meningitis. Overall, the results demonstrated that PCR in conjunction with sequencing may be a useful tool in the diagnosis of bacterial meningitis. PCR is particularly useful for analysing CSF from patients who have been treated with antibiotics before lumbar puncture.

Prognostic factors in adult community-acquired bacterial meningitis: a 4-year retrospective study

The aim of this 4-year, observational, single-center study was to identify prognostic factors and evaluate the need for intensive care in cases of bacterial meningitis. During the study period, 60 cases of adult bacterial meningitis were identified. Fifty-one patients were transferred to the intensive care unit at various times during their hospital stay. In the multivariate analysis, factors significantly associated with the need for mechanical ventilation and/or vasopressive drugs included comorbidity and a Glasgow coma score of less than 12 at hour 6 following presentation. The results indicate patients with a decreased level of consciousness, neurological deficit or comorbidity should be admitted to the intensive care unit at an early stage of illness. When patients lack these criteria 6 h following presentation, admission to the medical ward is reasonable.

Community-Acquired Recurrent Bacterial Meningitis in Adults

Community-acquired recurrent bacterial meningitis in adults is a relatively rare disease. All previous data were derived from small retrospective case series. We prospectively evaluated episodes of recurrent bacterial meningitis in a nationwide cohort study in The Netherlands. Thirty-four episodes of recurrent bacterial meningitis were identified among 31 patients; 3 patients experienced 2 episodes during the study period. The mean age was 43 years, and 25 (74%) of 34 episodes occurred in men. Predisposing conditions were involved in 26 (77%) of 34 episodes; the most common predisposing conditions were remote head injury (17 [53%] of 32 episodes) and cerebrospinal fluid (CSF) leakage (9 [32%] of 28 episodes). Lumbar puncture revealed an individual CSF indicator of bacterial meningitis for almost all episodes (88%). The outcome was death for 5 (15%) of 34 episodes; 1 additional patient had a suboptimal score on the Glasgow Outcome Scale. We conclude that most patients with recurrent meningitis are male and have predisposing conditions, which, in most cases, are remote head injury or CSF leakage.

Community-Acquired Bacterial Meningitis in Adults: Antibiotic Timing in Disease Course and Outcome

Despite improvements in diagnostic and therapeutic approach to adult patients with bacterial meningitis, the overall mortality rate is still high. The aim of this study was to evaluate antibiotic timing in the course and outcome of bacterial meningitis. Two hundred and eighty six patients with community-acquired bacterial meningitis aged 14 years and more were included in this retrospective cohort study. Observational period was between 1 January 1990 and 31 December 2004. To assess the association of antibiotic timing and disease outcome we analyzed three timing periods (according to the onset of disease, onset of consciousness disturbance and the time of admission to hospital). Analysis was also performed in a subgroup of culture positive meningitis in 176 patients with altered mental status. Unfavorable outcome was found in 125 (43,7%) patients. In this group, the start of appropriate antibiotic treatment in relation to the onset of first symptoms and particularly to the onset of consciousness disturbance was significantly delayed (p = 0.018 and p < 0.001, respectively) compared to the favorable group. Logistic regression analysis in a subgroup of culture positive meningitis in patients with altered mental status revealed that early adequate antibiotic treatment related to the onset of overt signs of meningitis was independently associated with favorable outcome (OR = 11.19; 95% CI 4.37-32.57; p < 0.001). Advanced age, lower GCS and seizures (OR = 1.05, OR = 1.45 and OR = 3.65, respectively) were other risk factors of poor outcome. The presence of chronic diseases, pneumococcal etiology and clinical and laboratory variables which are indicators of disease severity (renal and/or liver dysfunction, hypotension and low cerebrospinal fluid glucose) were not confirmed as independent risk factors of poor outcome. Our study emphasizes the importance of early and adequate antibiotic treatment in the management of bacterial meningitis which significantly enhances the chances for favorable outcome.

Nosocomial bacterial meningitis in adults: a prospective series of 50 cases

In order to evaluate characteristics of nosocomial meningitis in adults, we performed a prospective cohort study of 50 episodes of nosocomial bacterial meningitis. These cases were confirmed by culture of cerebrospinal fluid (CSF) in patients aged >16 years. Classic symptoms of bacterial meningitis (headache, neck stiffness and fever) were present in >70% of the episodes, although only a minority (41%) presented with impairment of consciousness. Underlying conditions, such as a history of neurosurgery, recent head injury, CSF leakage or a distant focus of infection, were present in 94% of the episodes. Staphylococcus aureus was the most common pathogen in patients with a history of neurosurgery, causing 10 of 32 episodes (31%). Patients with a distant focus of infection, such as otitis, sinusitis or pneumonia were more likely to have meningitis due to Streptococcus pneumoniae than patients without [six of nine episodes (67%) vs seven of 41 (17%); P=0.01]. Complications occurred in 50% of the episodes and 16% of the patients died. Our study confirms that adults with nosocomial meningitis are a distinct patient group with specific bacterial pathogens, as compared to those with community-acquired bacterial meningitis. Underlying conditions, especially a history of neurosurgery or a distant focus of infection, were present in the large majority of patients, and mortality and morbidity rates were high.

Therapy in Postpuncture Meningitis

We read with great interest the comprehensive overview by Baer1regarding post–dural puncture (bacterial) meningitis (PDPM). However, some questions can be raised regarding treatment recommendations for patients with PDPM.The recommendation for empiric treatment that is made in this article follows Infectious Diseases Society of America guidelines for Streptococcus pneumoniae meningitis.2In these guidelines, use of vancomycin plus the third-generation cephalosporins ceftriaxone or cefotaxime is recommended with the addition of ampicillin in patients older than 50 yr.2Of the 179 reviewed cases in this article, indeed, almost half had meningitis due to viridans streptococci; however, relatively high rates of Staphylococcus aureus (9 patients, 5%), Pseudomonas aeruginosa (8 patients, 4%), and Enterococcus faecalis (3 patients, 2%) were also found.1This specific distribution of species stresses that PDPM should be regarded as a specific category of patients that most resembles the “standard” category of patients with recent neurosurgery.3,4In this category, recent guidelines recommend vancomycin plus ceftazidime. Ceftazidime, and not ceftriaxone or cefotaxime, has shown efficacy in several studies of patients with Pseudomonas meningitis.2,5Alternatively, one can use cefepime, which also has greater in vitro activity than the third-generation cephalosporins.2,5In addition, Baer recommends the use of adjunctive dexamethasone in patients with PDPM.1In a recent European randomized clinical trial, adjunctive dexamethasone therapy reduced mortality from 15% to 7%.6Of the total of 301 included patients in this trial, 9 (3%) had meningitis due to viridans streptococci, and were partly described previously.7One of the 5 patients included in the placebo group died, versus 1 of the 4 in the dexamethasone group. Both patients died of S. milleri meningitis; others had meningitis due to S. salivarius (n = 4), S. sanguis (n = 2), and S. oralis (n = 1) (van de Beek, unpublished, October 2006). In a recent quantitative review of the effect of adjunctive dexamethasone in adults with community-acquired bacterial meningitis that included the results of five clinical trials, treatment with dexamethasone was associated with a significant reduction in mortality and neurologic sequelae.8On basis of these data, dexamethasone is advised for patients with suspected or proven community-acquired bacterial meningitis and should be continued for 4 days, regardless of microbial cause.5However, PDPM has a different pathophysiology, and cerebrospinal fluid cultures yielded specific distribution of causative species, as compared with patients with community-acquired bacterial meningitis.1,9Therefore, adjunctive dexamethasone is not recommended in the subgroup of patients with PDPM.*Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. d.vandebeek@amc.uva.nlor vandebeek.diederik@mayo.edu

P1259 Host susceptibility to accute community-acquired bacterial meningitis: multicentre study of genetic markers

P1259 Host susceptibility to accute community-acquired bacterial meningitis: multicentre study of genetic markers

O419 Management of community-acquired bacterial meningitis

O419 Management of community-acquired bacterial meningitis

Procoagulant and fibrinolytic activity in cerebrospinal fluid from adults with bacterial meningitis

This study investigated levels of coagulation and fibrinolysis factors in cerebrospinal fluid (CSF) from adults with bacterial meningitis in relation to development of brain infarction. CSF was collected from 92 adults with community-acquired bacterial meningitis, who participated in the prospective Dutch Meningitis Cohort Study; 8 patients with viral meningitis and 9 healthy control subjects. Levels of proteins involved in the coagulation cascade were determined by means of immunoassays. Bacterial meningitis was accompanied by local activation of coagulation, as shown by significantly higher CSF soluble tissue factor (P<0.001) and prothrombin fragment F1+2 concentrations (P<0.001) as compared to viral meningitis patients and controls. This was accompanied by a significantly higher D-dimer formation (P<0.001). In addition, in bacterial meningitis fibrinolysis was attenuated, since CSF plasminogen activator inhibitor (PAI)-1 levels were significantly higher as compared to the controls (P=0.02). In patients with bacterial meningitis who developed brain infarction, CSF PAI-1 levels were higher than in those without infarction (P=0.04). Activation of coagulation and attenuation of fibrinolysis in the CSF are important features of bacterial meningitis; the net effect on fibrin turnover may contribute to the development of brain infarction.