Martijn Weisfelt

Clinical features, complications, and outcome in adults with pneumococcal meningitis: a prospective case series

BACKGROUND Bacterial meningitis is a grave disease of high incidence, especially in less developed countries. Here, we describe its clinical presentation, spectrum of complications, prognostic factors, and outcome in adults with pneumococcal meningitis. METHODS From October, 1998, to April, 2002, we assessed 352 episodes of community-acquired pneumococcal meningitis, confirmed by culture of cerebrospinal fluid (CSF), which occurred in patients older than 16 years. Predictors for an unfavourable outcome (Glasgow outcome scale score 1-4) were identified by logistic regression with multiple imputation techniques. FINDINGS 245 (70%) episodes of pneumococcal meningitis were associated with an underlying disorder. Cranial CT was done for 85% of episodes and revealed underlying disorders in 17% (50/299) and meningitis-associated intracranial complications in 39% (117/299). Independent predictors for an unfavourable outcome were a low score on the Glasgow coma scale, cranial nerve palsies, a raised erythrocyte sedimentation rate, a CSF leucocyte count less than 1000 cells per mm(3), and a high CSF protein concentration on admission. Overall in-hospital mortality was 30%. Prevalence of neurological and systemic complications did not differ between patients aged younger than 60 years and those aged 60 years and older; however, systemic complications were the cause of death in 59% (32/54) of fatal episodes in patients aged 60 years and older, whereas neurological complications were the cause of death in 65% (20/31) of fatal episodes in younger patients. INTERPRETATION Pneumococcal meningitis is associated with high mortality and morbidity rates in adults. Whereas neurological complications are the leading cause of death in younger patients, elderly patients die predominantly from systemic complications.

Cognitive Impairment in Adults with Good Recovery after Bacterial Meningitis

Adults without neurologic sequelae after bacterial meningitis are supposed to live without restrictions. Neuropsychological outcome was assessed in 51 adults from a prospective cohort with good recovery, defined as Glasgow Outcome Scale score 5, after pneumococcal or meningococcal meningitis. Patients who recovered well after pneumococcal meningitis showed cognitive slowness (P=.001). A cognitive disorder was found in 27% of these patients. Patients who previously had meningococcal meningitis were not significantly different from control subjects. Scores on general health and quality of life questionnaires revealed lower scores for patients with meningitis, which were related to cognitive slowing (R, -0.46 to -0.38). In conclusion, adults surviving pneumococcal meningitis were at significant risk of neuropsychological abnormalities, even if they were clinically well recovered.

Cognitive outcome in adults after bacterial meningitis

Objective: To evaluate cognitive outcome in adult survivors of bacterial meningitis. Methods: Data from three prospective multicentre studies were pooled and reanalysed, involving 155 adults surviving bacterial meningitis (79 after pneumococcal and 76 after meningococcal meningitis) and 72 healthy controls. Results: Cognitive impairment was found in 32% of patients and this proportion was similar for survivors of pneumococcal and meningococcal meningitis. Survivors of pneumococcal meningitis performed worse on memory tasks (p<0.001) and tended to be cognitively slower than survivors of meningococcal meningitis (p = 0.08). We found a diffuse pattern of cognitive impairment in which cognitive speed played the most important role. Cognitive performance was not related to time since meningitis; however, there was a positive association between time since meningitis and self-reported physical impairment (p<0.01). The frequency of cognitive impairment and the numbers of abnormal test results for patients with and without adjunctive dexamethasone were similar. Conclusions: Adult survivors of bacterial meningitis are at risk of cognitive impairment, which consists mainly of cognitive slowness. The loss of cognitive speed is stable over time after bacterial meningitis; however, there is a significant improvement in subjective physical impairment in the years after bacterial meningitis. The use of dexamethasone was not associated with cognitive impairment.

Pneumococcal meningitis in adults: new approaches to management and prevention

Since the virtual eradication of meningitis due to Haemophilus influenzae type B by vaccination in the developed world, pneumococcal meningitis has become the leading cause of bacterial meningitis beyond the neonatal period. Clinical and experimental research has increased our knowledge about the pathophysiology and pathogenesis of the disease over the past decades. Despite the availability of effective antibiotics, supportive care facilities, and recent advances in adjunctive strategies-ie, adjunctive dexamethasone-mortality and morbidity rates associated with pneumococcal meningitis remain unacceptably high. Although preliminary results after the introduction of the pneumococcal conjugate vaccine are promising, the incidence of multidrug-resistant pneumococcal strains is rising worldwide. Here we discuss clinical aspects of pneumococcal meningitis in adults, with focus on pathophysiology, and stress the urgent need for adequate preventive measures and new effective treatments.

The Preventive Antibiotics in Stroke Study (PASS): a pragmatic randomised open-label masked endpoint clinical trial

BACKGROUND In adults with acute stroke, infections occur commonly and are associated with an unfavourable functional outcome. In the Preventive Antibiotics in Stroke Study (PASS) we aimed to establish whether or not preventive antimicrobial therapy with a third-generation cephalosporin, ceftriaxone, improves functional outcome in patients with acute stroke. METHODS In this multicentre, randomised, open-label trial with masked endpoint assessment, patients with acute stroke were randomly assigned to intravenous ceftriaxone at a dose of 2 g, given every 24 h intravenously for 4 days, in addition to stroke unit care, or standard stroke unit care without preventive antimicrobial therapy; assignments were made within 24 h after symptom onset. The primary endpoint was functional outcome at 3 months, defined according to the modified Rankin Scale and analysed by intention to treat. The primary analysis was by ordinal regression of the primary outcome. Secondary outcomes included death, infection rates, antimicrobial use, and length of hospital stay. Participants and caregivers were aware of treatment allocation but assessors of outcome were masked to group assignment. This trial is registered with controlled-trials.com, number ISRCTN66140176. FINDINGS Between July 6, 2010, and March 23, 2014, a total of 2550 patients from 30 sites in the Netherlands, including academic and non-academic medical centres, were randomly assigned to the two treatment groups: 1275 patients to ceftriaxone and 1275 patients to standard treatment (control group). 12 patients (seven in the ceftriaxone group and five in the control group) withdrew consent immediately after randomisation, leaving 2538 patients available for the intention-to-treat-analysis (1268 in the ceftriaxone group and 1270 in the control group). 2514 (99%) of 2538 patients (1257 in each group) completed 3-month follow-up. Preventive ceftriaxone did not affect the distribution of functional outcome scores on the modified Rankin Scale at 3 months (adjusted common odds ratio 0·95 [95% CI 0·82-1·09], p=0·46). Preventive ceftriaxone did not result in an increased occurrence of adverse events. Overgrowth infection with Clostridium difficile occurred in two patients (<1%) in the ceftriaxone group and none in the control group. INTERPRETATION Preventive ceftriaxone does not improve functional outcome at 3 months in adults with acute stroke. The results of our trial do not support the use of preventive antibiotics in adults with acute stroke. FUNDING Netherlands Organization for Health Research and Development, Netherlands Heart Foundation, and the European Research Council.

Clinical features, outcome, and meningococcal genotype in 258 adults with meningococcal meningitis: a prospective cohort study.

Abstract 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. Abbreviations: cc = clonal complex, CRP = C-reactive protein, CSF = cerebrospinal fluid, CT = computed tomography, ESR = erythrocyte sedimentation rate, GCS = Glasgow Coma Scale, IQR = interquartile range, MLST = multi-locus sequence typing, WBCC = white blood cell count.

Dexamethasone and long-term outcome in adults with bacterial meningitis.

This follow‐up study of the European Dexamethasone Study was designed to examine the potential harmful effect of adjunctive dexamethasone treatment on long‐term neuropsychological outcome in adults with bacterial meningitis.

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/mm3 (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.

Community‐Acquired Bacterial Meningitis in Older People

OBJECTIVES: To describe clinical features of bacterial meningitis in older people.

A Risk Score for Unfavorable Outcome in Adults with Bacterial Meningitis

To derive and validate a bedside risk score for adverse outcome in adults with bacterial meningitis.