Nationwide implementation of adjunctive dexamethasone therapy for pneumococcal meningitis.

BACKGROUND: In this nationwide prospective cohort study, we evaluated the implementation of adjunctive dexamethasone therapy in Dutch adults with pneumococcal meningitis. METHODS: From March 2006 through January 2009, all Dutch patients over 16 years old with community-acquired pneumococcal meningitis were prospectively evaluated. Outcome was classified as unfavorable (defined by a Glasgow Outcome Scale score of 1 to 4 points at discharge) or favorable (a score of 5). Clinical characteristics and outcome were compared with a similar nationwide cohort of 352 patients with pneumococcal meningitis from a previous period before guidelines recommended dexamethasone therapy (1998-2002). A multivariable prognostic model was used to adjust for differences in case mix between the 2 cohorts. RESULTS: We evaluated 357 episodes with pneumococcal meningitis in 2006-2009. Characteristics on admission were comparable with the earlier cohort (1998-2002). Dexamethasone was started with or before the first dose of antibiotics in 84% of episodes in 2006-2009 and 3% in 1998-2002. At discharge, unfavorable outcome was present in 39% in 2006-2009 and 50% in 1998-2002 (odds ratio [OR] 0.63; 95% confidence interval [CI] 0.46-0.86; p = 0.002). Rates of death (20% vs 30%; p = 0.001) and hearing loss (12% vs 22%; p = 0.001) were lower in 2006-2009. Differences in outcome remained after adjusting for differences in case mix between cohorts. CONCLUSIONS: Dexamethasone therapy has been implemented on a large scale as adjunctive treatment of adults with pneumococcal meningitis in the Netherlands. The prognosis of pneumococcal meningitis on a national level has substantially improved after the introduction of adjunctive dexamethasone therapy. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that dexamethasone (10 mg IV, given every 6 hours for 4 days started before or with the first dose of parenteral antibiotics) reduced the proportion of patients with unfavorable outcomes (Glasgow Outcome Scale score of 1 to 4) in the 2006-2009 cohort, as compared to the 1998-2002 cohort (39% vs 50%; OR 0.63; 95% CI 0.46-0.86; p = 0.002). Mortality rate (20% vs 30%; absolute risk difference 10%; 95% CI 4%-17%; p = 0.001) was also lower in 2006-2009.

Delayed cerebral thrombosis after initial good recovery from pneumococcal meningitis.

OBJECTIVE: To report an unusual clinical course in 6 patients with community-acquired acute bacterial meningitis and to compare clinical features with cases reported in the literature. METHODS: Case series from Dutch hospitals from 2003 to 2008. RESULTS: Five out of six patients were male, age ranged from 30 to 73 years (mean age, 47 years). All patients had pneumococcal meningitis, received adjunctive dexamethasone treatment on admission, and made a good or excellent initial recovery. After 7 to 19 days, patients suddenly deteriorated, developing headache, fever, a decreased level of consciousness, brainstem signs, or hemiparesis. Imaging studies showed infarctions involving the thalamus or brainstem in all patients. Repeated lumbar puncture showed a pleocytosis, but CSF cultures were sterile. Five patients were treated with high-dose steroids on deterioration. Outcome was poor: 4 patients died and 2 remained disabled. Autopsies, performed in 2 patients, showed infarctions predominantly involving the posterior circulation territory, thrombosis in penetrating arteries, but no evidence of vasculitis. We identified 5 meningitis cases with delayed vasculopathy in the literature, but these patients did not exactly resemble the clinical course of our patients. CONCLUSIONS: Delayed cerebral thrombosis may occur in patients with excellent recovery from pneumococcal meningitis. All patients were treated initially with adjunctive dexamethasone therapy, suggesting a dexamethasone-associated effect. Pathology suggests an immunologic reaction targeting cerebral blood vessels.

[Tick-borne disease or not? Do not let yourself be fooled]. / Tekenbeetziekte ofniet? Laat u niet beetnemen.

Confusion among physicians and patients is increasing regarding the diagnosis and treatment ofLyme borreliosis due to the enormous amount ofambiguous information available and media attention. Some of the dilemmas that physicians encounter are illustrated by 3 patients with a range of symptoms, one of whom was convinced she had Lyme borreliosis. However none of these patients had significant evidence that suggested Lyme borreliosis. Physicians should follow the guidelines developed by the Dutch Institute for Health Care Improvement (CBO) or the Infectious Diseases Society of America rather than 'alternative' guidelines, which are not evidence-based.

Seizures in adults with bacterial meningitis.

OBJECTIVE: To evaluate the occurrence and prognostic relevance of seizures in adults with community-acquired bacterial meningitis. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

Community-acquired Haemophilus influenzae meningitis in adults.

Haemophilus influenzae is an uncommon cause of bacterial meningitis in adults. This report describes a prospective evaluation of 16 episodes of community-acquired H. influenzae meningitis in a nationwide study on bacterial meningitis. Predisposing conditions were present in eight (50%) of the 16 episodes; the most common predisposing conditions were otitis or sinusitis (five episodes; 31%) and remote neurosurgery or head trauma (three episodes; 19%). One (6%) episode was fatal and hearing loss occurred in four (25%) episodes. It was concluded that H. influenzae meningitis in adults is a disease with a rather benign clinical course and a relatively good prognosis compared with pneumococcal meningitis.

Corticosteroids for acute bacterial meningitis.

BACKGROUND: In experimental studies, the clinical outcome of acute bacterial meningitis has been related to the severity of the inflammatory process in the subarachnoidal space. Treatment with corticosteroids can reduce this inflammatory response and thereby may improve outcome. We conducted a meta-analysis of randomised controlled trials (RCTs) of adjuvant corticosteroids in the treatment of acute bacterial meningitis. OBJECTIVES: We conducted a systematic review examining the efficacy and safety of adjuvant corticosteroid therapy in acute bacterial meningitis. SEARCH STRATEGY: In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2006); MEDLINE (1966 to July 2006); EMBASE (1974 to June 2006); Current Contents (2001 to June 2006); and reference lists of all articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Eligible published and non-published RCTs on corticosteroids as adjuvant therapy in acute bacterial meningitis. Patients of any age and in any clinical condition, treated with antibacterial agents and randomised to corticosteroid therapy (or placebo) of any type, could be included. At least case fatality rate or hearing loss had to be recorded for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Adverse effects were collected from the trials. Additional analyses were performed for children and adults, causative organisms, and low-income and developed countries. MAIN RESULTS: Eighteen studies involving 2750 people were included. Overall, adjuvant corticosteroids were associated with lower case fatality (relative risk (RR) 0.83, 95% CI 0.71 to 0.99), lower rates of severe hearing loss (RR 0.65, 95% CI 0.47 to 0.91) and long-term neurological sequelae (RR 0.67, 95% CI 0.45 to 1.00). In children, corticosteroids reduced severe hearing loss (RR 0.61, 95% CI 0.44 to 0.86). In adults, corticosteroids gave significant protection against death (RR 0.57, 95% CI 0.40 to 0.81) and short-term neurological sequelae (RR 0.42, 95% CI 0.22 to 0.87). Subgroup analysis for causative organisms showed that corticosteroids reduced mortality in patients with meningitis due to Streptococcus pneumoniae (RR 0.59, 95% CI 0.45 to 0.77) and reduced severe hearing loss in children with meningitis due to Haemophilus influenzae (RR 0.37, 95% CI 0.20 to 0.68); subgroup analysis for patients with meningococcal showed a nonsignificant favourable trend in mortality (RR 0.71, 95% CI 0.31 to 1.62). Sub analyses for high-income and low-income countries of the effect of corticosteroids on mortality showed RRs of 0.83 (95% CI 0.52 to 1.05) and 0.87 (95% CI 0.72 to 1.05), respectively. Corticosteroids were protective against short-term neurological sequelae in patients with bacterial meningitis high-income countries (RR 0.56, 95% CI 0.3 to 0.84); in low-income countries this RR was 1.09 (95% CI 0.83 to 1.45). For children with bacterial meningitis admitted in high-income countries, corticosteroids showed a protective effect of on severe hearing loss (RR 0.61, 95% CI 0.41 to 0.90) and favourable point estimates for severe hearing loss associated with non-Haemophilus influenzae meningitis (RR 0.51, 95% CI 0.23 to 1.13) and short-term neurological sequelae (RR 0.72, 95% CI 0.39 to 1.33). For children in low-income countries, the use of corticosteroids was neither associated with benefit nor with harmful effects. Overall, adverse events were not increased significantly with the use of corticosteroids. AUTHORS' CONCLUSIONS: Overall, corticosteroids significantly reduced rates of mortality, severe hearing loss and neurological sequelae. In adults with community-acquired bacterial meningitis, corticosteroid therapy should be administered in conjunction with the first antibiotic dose. In children, data support the use of adjunctive corticosteroids in children in high-income countries. We found no beneficial effect of corticosteroids for children in low-income countries.

Hyponatraemia in adults with community-acquired bacterial meningitis.

BACKGROUND: Hyponatraemia in adults with bacterial meningitis has been described as a common complication, but its true prevalence and clinical importance are unknown. AIM: To investigate the prevalence, clinical characteristics and consequences of hyponatraemia in bacterial meningitis in adults. DESIGN: Nationwide observational cohort study. METHODS: We prospectively assessed the prevalence and clinical characteristics of hyponatraemia among 696 adults with community-acquired bacterial meningitis. Symptoms and signs on admission, blood and CSF test results, radiological examinations and complications during admission were recorded. RESULTS: Sodium levels were determined at admission in 685/696 episodes of bacterial meningitis (98%). Hyponatraemia (<135 mmol/l) was seen in 208/685 (30%) and was classified as severe (<130 mmol/l) in 38 (6%). Hyponatraemia developed during admission in an additional 53 episodes. Hyponatraemia was not associated with an increase in symptoms, with complications or with unfavourable outcome. Treatment for hyponatraemia was initiated in 16% of episodes, but did not influence its duration. DISCUSSION: Hyponatraemia appears both common and benign in adults with bacterial meningitis. In cases of severe hyponatraemia, we suggest the use of fluid maintenance therapy.

Dexamethasone treatment in adults with pneumococcal meningitis: risk factors for death.

In experimental meningitis, adjunctive treatment with steroids reduces cerebrospinal fluid inflammation and thereby improves neurological outcome. On the basis of these findings, several clinical trials have assessed treatment with adjunctive steroids in bacterial meningitis, with conflicting results. Recently, the results of the European Dexamethasone Study showed a beneficial effect of adjunctive dexamethasone in adults with bacterial meningitis. In that study, the effect of dexamethasone on outcome was most striking in patients with pneumococcal meningitis. The aim of the present study was to further evaluate the effect of dexamethasone in adults with pneumococcal meningitis by performing a post hoc analysis of the European Dexamethasone Study. In a multivariate analysis, tachycardia (p=0.02), advanced age (p=0.03), low score on the Glasgow Coma Scale (p=0.03), positive blood culture (p=0.04), and absence of dexamethasone therapy (p=0.05) were independent predictors for death. Patients who were treated with adjunctive dexamethasone were less likely to develop both systemic and neurological complications during hospitalisation, compared with patients who received placebo. In conclusion, independent risk factors for death in pneumococcal meningitis are tachycardia, advanced age, low level of consciousness, bacteraemia, and absence of dexamethasone therapy. Treatment with adjunctive dexamethasone in adults with pneumococcal meningitis reduces both systemic and neurological complications.

[Loss of cranial-nerve function caused by early syphilitic meningitis: the comeback of a pre-war syndrome]. / Hersenzenuwuitval door vroege syfilitische meningitis: terugkeer van een vooroorlogs ziektebeeld.

Two men aged 39 and 38 who had had unprotected insertive and receptive anal sexual contact with men are presented: one had paralysis of the right half of his face and the other man had erythematous macules on the palms of his hands and the soles of his feet as well as partial alopecia, earache and progressive loss of hearing in his left ear. The latter one was also HIV-seropositive and on antiretroviral medication. Syphilitic meningitis was diagnosed in both men. The 2 patients recovered after being treated with intravenous benzyl penicillin. Syphilitic meningitis is a complication seen during the early stages of a syphilis infection. Since the introduction of penicillin it has become a rare disease. Early diagnosis is of importance since syphilitic meningitis has irreversible sequelae.

Corticosteroids in acute bacterial meningitis.

BACKGROUND: Acute bacterial meningitis remains a disease with high mortality rate, ranging from 10 to 30 percent, despite advances in critical care. It has been estimated that between 5 to 40 percent of all patients can suffer hearing loss. The use of corticosteroids as adjuvant therapy in the treatment of acute bacterial meningitis is controversial despite several controlled clinical trials and three meta-analyses. In particular there are few data on the use of corticosteroids in adult meningitis. OBJECTIVES: We conducted a systematic review examining the efficacy and safety of adjuvant corticosteroid therapy in children and adults with acute bacterial meningitis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library issue 1, 2003)); MEDLINE (1966 to April 2002); EMBASE (1974 to April 2002); and HEALTHLINE (1988 to April 2002) and Current Contents for trials published before the April 1st 2002, and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Eligible studies were published or non-published randomised controlled trials on corticosteroids as adjuvant therapy in acute bacterial meningitis. Patients of any age and in any clinical condition, treated with antibacterial agents and randomised to corticosteroid therapy (or placebo) of any type, could be included. At least case fatality rate or hearing loss had to be recorded for inclusion. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Eighteen studies involving 1853 people were included. Overall, adjuvant corticosteroids were associated with lower case fatality (relative risk (RR) 0.76, 95% confidence intervals (CI) 0.59 to 0.98) and lower rates of both severe hearing loss (RR 0.36, 95% CI 0.22 to 0.60) and long-term neurological sequelae (RR 0.66, 95% CI 0.44 to 0.99). In children, corticosteroids reduced severe hearing loss in bacterial meningitis caused by Haemophilus influenzae (RR 0.31, 95% CI 0.15 to 0.62), as well as in meningitis caused by other bacteria than H. influenzae (RR 0.42, 95%CI 0.20 to 0.89). In adults there was a reduction in case-fatality (RR 0.38, 95% CI 0.18 to 0.78), however there were few data. Adverse events were not increased significantly with the use of corticosteroids. REVIEWER'S CONCLUSIONS: Adjuvant corticosteroids are beneficial in the treatment of children with acute bacterial meningitis. The limited data available in adults shows a trend in favour of adjuvant corticosteroids but a definite recommendation must await more studies. ERRATUM: During the review process of this systematic review the results of the European Dexamethasone in Adulthood Bacterial Meningitis Trial were published. (De Gans 2002) In this prospective, randomised, double-blind, multicenter trial, which included 301 adults with bacterial meningitis, treatment with dexamethasone was associated with a reduction in mortality (relative risk of death, 0.48; 95 CI 0.24 to 0.96; p = 0.04). Therefore, dexamethasone should be given to all adults with bacterial meningitis and should be initiated before or with the first dose of antibiotics.

Lumbar puncture and the risk of herniation: when should we first perform CT?

Death following lumbar puncture (LP) is feared by physicians. Many opinions are found in literature on the question whether computed cranial tomography (CT) should be performed before LP, to prevent herniation. These opinions are mainly based on retrospective studies and pathophysiological reasoning. In this review the difficulties in the decision whether we should perform CT before LP are discussed. It is explained that the concept of "raised intracranial pressure" is confusing, and that the less ambiguous terms "brain shift" and "raised CSF pressure" should be used instead. Brain shift is a contraindication to LP, whether CSF pressure is raised or not, and whether papilloedema is present or not. Subsequently, recommendations are offered for indications to perform CT before LP, grouped according to the safety and clinical utility of LP.

Placebo effect in the acute treatment of migraine: subcutaneous placebos are better than oral placebos.

We carried out a meta-analysis of 22 trials to determine the comparative placebo effect of (a) subcutaneous vs. oral and (b) in-hospital vs. at-home administration in the treatment of migraine. The headache relief rates were combined from the placebo arms of these randomised clinical trials assessing the value of sumatriptan in acute treatment of migraine. The main outcome measure was the proportion of patients reclassified from severe or moderate headache severity to no or mild headache severity 2 h after the beginning of treatment. In the oral regimen 222 of 865 patients (25.7%) reported no or mild headache severity after 2 h, compared to 279 of 862 patients (32.4%) of those receiving subcutaneous placebo (6.7% difference; 95% CI 2.4-11.0%). Adjusting for treatment setting and severity of headache at baseline did not change the observed difference. After placebo treatment at home 285 of 1,054 patients (27.0%) reported no or mild headache severity after 2 h, compared to 216 of 673 patients (32.1%) among those receiving placebo in hospital (5.1 % difference; 95% CI 0.6-9.5%). When adjusted for route of administration and severity of headache at baseline, the difference in relief rates between home and hospital setting disappeared. These findings indicate that subcutaneous administration enhances the placebo effect of acute treatment of migraine. Future trials of antimigraine drugs assessing the relative efficacy of various routes of administration should use a double-dummy technique. The interpreting of placebo-controlled trial results must therefore consider that the effect in the drug arm of the trial depends in part on the route of administration.

Meningitis due to viridans streptococci in adults.

Seven patients are reported with meningitis due to viridans streptococci. These patients represented 5% of culture-proven cases of bacterial meningitis in adults participating in a prospective multicentre clinical trial evaluating the use of dexamethasone. Meningitis was iatrogenic in three patients: one patient had been treated with endoscopic sclerotherapy for oesophageal varices, and two patients had undergone thermocoagulation of the gasserian ganglion for trigeminal neuralgia in the previous days.

Meropenem susceptibility of Neisseria meningitidis and Streptococcus pneumoniae from meningitis patients in The Netherlands.

In-vitro susceptibility of 299 Neisseria meningitidis and 157 Streptococcus pneumoniae strains from meningitis patients in The Netherlands in 1993 and 1994 to meropenem was determined using the Etest. Susceptibility to penicillin, ceftriaxone, and chloramphenicol was also determined. Rifampicin susceptibility was additionally tested for N. meningitidis. Of the meningococci, 4.3% were of intermediate resistance to penicillin and 0.3% were resistant to rifampicin. One pneumococcal isolate (0.6%) was of intermediate resistance to penicillin. All strains were susceptible to meropenem. We conclude that meropenem is in vitro highly active against N. meningitidis and S. pneumoniae.