-
Current Opinion in Neurology Jun 2021Community-acquired bacterial meningitis is a continually changing disease. This review summarises both dynamic epidemiology and emerging data on pathogenesis. Updated... (Review)
Review
PURPOSE OF REVIEW
Community-acquired bacterial meningitis is a continually changing disease. This review summarises both dynamic epidemiology and emerging data on pathogenesis. Updated clinical guidelines are discussed, new agents undergoing clinical trials intended to reduce secondary brain damage are presented.
RECENT FINDINGS
Conjugate vaccines are effective against serotype/serogroup-specific meningitis but vaccine escape variants are rising in prevalence. Meningitis occurs when bacteria evade mucosal and circulating immune responses and invade the brain: directly, or across the blood-brain barrier. Tissue damage is caused when host genetic susceptibility is exploited by bacterial virulence. The classical clinical triad of fever, neck stiffness and headache has poor diagnostic sensitivity, all guidelines reflect the necessity for a low index of suspicion and early Lumbar puncture. Unnecessary cranial imaging causes diagnostic delays. cerebrospinal fluid (CSF) culture and PCR are diagnostic, direct next-generation sequencing of CSF may revolutionise diagnostics. Administration of early antibiotics is essential to improve survival. Dexamethasone partially mitigates central nervous system inflammation in high-income settings. New agents in clinical trials include C5 inhibitors and daptomycin, data are expected in 2025.
SUMMARY
Clinicians must remain vigilant for bacterial meningitis. Constantly changing epidemiology and emerging pathogenesis data are increasing the understanding of meningitis. Prospects for better treatments are forthcoming.
Topics: Anti-Bacterial Agents; Headache; Humans; Meningitis, Bacterial; Spinal Puncture
PubMed: 33767093
DOI: 10.1097/WCO.0000000000000934 -
Clinical Microbiology Reviews Apr 2022Neonatal bacterial meningitis is a devastating disease, associated with high mortality and neurological disability, in both developed and developing countries.... (Review)
Review
Neonatal bacterial meningitis is a devastating disease, associated with high mortality and neurological disability, in both developed and developing countries. Streptococcus agalactiae, commonly referred to as group B Streptococcus (GBS), remains the most common bacterial cause of meningitis among infants younger than 90 days. Maternal colonization with GBS in the gastrointestinal and/or genitourinary tracts is the primary risk factor for neonatal invasive disease. Despite prophylactic intrapartum antibiotic administration to colonized women and improved neonatal intensive care, the incidence and morbidity associated with GBS meningitis have not declined since the 1970s. Among meningitis survivors, a significant number suffer from complex neurological or neuropsychiatric sequelae, implying that the pathophysiology and pathogenic mechanisms leading to brain injury and devastating outcomes are not yet fully understood. It is imperative to develop new therapeutic and neuroprotective approaches aiming at protecting the developing brain. In this review, we provide updated clinical information regarding the understanding of neonatal GBS meningitis, including epidemiology, diagnosis, management, and human evidence of the disease's underlying mechanisms. Finally, we explore the experimental models used to study GBS meningitis and discuss their clinical and physiologic relevance to the complexities of human disease.
Topics: Anti-Bacterial Agents; Female; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Meningitis, Bacterial; Streptococcal Infections; Streptococcus agalactiae
PubMed: 35170986
DOI: 10.1128/cmr.00079-21 -
Clinical Microbiology Reviews Jul 2010The epidemiology of bacterial meningitis has changed as a result of the widespread use of conjugate vaccines and preventive antimicrobial treatment of pregnant women.... (Review)
Review
The epidemiology of bacterial meningitis has changed as a result of the widespread use of conjugate vaccines and preventive antimicrobial treatment of pregnant women. Given the significant morbidity and mortality associated with bacterial meningitis, accurate information is necessary regarding the important etiological agents and populations at risk to ascertain public health measures and ensure appropriate management. In this review, we describe the changing epidemiology of bacterial meningitis in the United States and throughout the world by reviewing the global changes in etiological agents followed by specific microorganism data on the impact of the development and widespread use of conjugate vaccines. We provide recommendations for empirical antimicrobial and adjunctive treatments for clinical subgroups and review available laboratory methods in making the etiological diagnosis of bacterial meningitis. Finally, we summarize risk factors, clinical features, and microbiological diagnostics for the specific bacteria causing this disease.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Vaccines; Bacteriological Techniques; Cross Infection; Humans; Immunocompromised Host; Meningitis, Bacterial
PubMed: 20610819
DOI: 10.1128/CMR.00070-09 -
Clinical Microbiology and Infection :... May 2016
Topics: Anti-Bacterial Agents; Community-Acquired Infections; Humans; Meningitis, Bacterial; Meningitis, Pneumococcal; Patient Participation; Practice Guidelines as Topic
PubMed: 27062097
DOI: 10.1016/j.cmi.2016.01.007 -
Clinics in Perinatology Mar 2015Neonatal bacterial meningitis is uncommon but devastating. Morbidity among survivors remains high. The types and distribution of pathogens are related to gestational... (Review)
Review
Neonatal bacterial meningitis is uncommon but devastating. Morbidity among survivors remains high. The types and distribution of pathogens are related to gestational age, postnatal age, and geographic region. Confirming the diagnosis is difficult. Clinical signs are often subtle, lumbar punctures are frequently deferred, and cerebrospinal fluid (CSF) cultures can be compromised by prior antibiotic exposure. Infants with bacterial meningitis can have negative blood cultures and normal CSF parameters. Promising tests such as the polymerase chain reaction require further study. Prompt treatment with antibiotics is essential. Clinical trials investigating a vaccine for preventing neonatal Group B Streptococcus infections are ongoing.
Topics: Anti-Bacterial Agents; Bacterial Vaccines; Culture Techniques; Escherichia coli Infections; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Very Low Birth Weight; Meningitis, Bacterial; Spinal Puncture; Streptococcal Infections; Streptococcus agalactiae
PubMed: 25677995
DOI: 10.1016/j.clp.2014.10.004 -
Clinical Microbiology and Infection :... Sep 2017The existing heterogeneity in diagnostic work-up and treatment strategies in bacterial meningitis was the incentive to develop a European evidence-based guideline, which... (Review)
Review
BACKGROUND
The existing heterogeneity in diagnostic work-up and treatment strategies in bacterial meningitis was the incentive to develop a European evidence-based guideline, which was published in 2016 by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group on Infections of the Brain (ESGIB).
AIMS
To summarize salient features of the guideline, identify recent developments and challenges currently faced.
SOURCES
The ESCMID guideline, ongoing trial registries.
CONTENT
Epidemiology, clinical symptoms, diagnostic work-up and therapy strategies of acute bacterial meningitis.
IMPLICATIONS
The incidence of bacterial meningitis has decreased following pneumococcal and meningococcal conjugate vaccine introduction. In the diagnosis of bacterial meningitis the clinical characteristics and laboratory parameters are of limited diagnostic accuracy and therefore cerebrospinal fluid analysis remains the principal contributor to the final diagnosis. The ESCMID guideline advises to start empiric treatment within one hour of arrival in all suspected meningitis cases, and choice of antibiotics needs to be differentiated according to the patient's age, risk factors, and local resistance rates of pneumococci. Dexamethasone is the only proven adjunctive treatment and should be started together with the antibiotics. The follow-up of surviving patients should include evaluation for hearing loss and pneumococcal vaccination to prevent recurrences. Future perspectives include further development and implementation of vaccines, and new treatments aimed at further reducing the inflammatory response. Studies on implementation of the new guideline should determine adherence and evaluate whether improved prognosis can be achieved by following protocolled management strategies.
Topics: Community-Acquired Infections; Humans; Meningitis, Bacterial; Practice Guidelines as Topic
PubMed: 28478238
DOI: 10.1016/j.cmi.2017.04.019 -
PloS One 2018Bacterial meningitis is a global public health concern, with several responsible etiologic agents that vary by age group and geographical area. The aim of this... (Meta-Analysis)
Meta-Analysis
Bacterial meningitis is a global public health concern, with several responsible etiologic agents that vary by age group and geographical area. The aim of this systematic review and meta-analysis was to assess the etiology of bacterial meningitis in different age groups across global regions. PubMed and EMBASE were systematically searched for English language studies on bacterial meningitis, limited to articles published in the last five years. The methodological quality of the studies was assessed using a customized scoring system. Meta-analyses were conducted to determine the frequency (percentages) of seven bacterial types known to cause meningitis: Escherichia coli, Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, group B Streptococcus agalactiae, Staphylococcus aureus, and Listeria monocytogenes, with results being stratified by six geographical regions as determined by the World Health Organization, and seven age groups. Of the 3227 studies retrieved, 56 were eligible for the final analysis. In all age groups, S. pneumoniae and N. meningitidis were the predominant pathogens in all regions, accounting for 25.1-41.2% and 9.1-36.2% of bacterial meningitis cases, respectively. S. pneumoniae infection was the most common cause of bacterial meningitis in the 'all children' group, ranging from 22.5% (Europe) to 41.1% (Africa), and in all adults ranging from 9.6% (Western Pacific) to 75.2% (Africa). E. coli and S. pneumoniae were the most common pathogens that caused bacterial meningitis in neonates in Africa (17.7% and 20.4%, respectively). N. meningitidis was the most common in children aged ±1-5 years in Europe (47.0%). Due to paucity of data, meta-analyses could not be performed in all age groups for all regions. A clear difference in the weighted frequency of bacterial meningitis cases caused by the different etiological agents was observed between age groups and between geographic regions. These findings may facilitate bacterial meningitis prevention and treatment strategies.
Topics: Age Factors; Databases, Factual; Humans; Meningitis, Bacterial; Neisseria meningitidis; Risk Factors; Streptococcus pneumoniae
PubMed: 29889859
DOI: 10.1371/journal.pone.0198772 -
The New England Journal of Medicine Oct 2004We conducted a nationwide study in the Netherlands to determine clinical features and prognostic factors in adults with community-acquired acute bacterial meningitis.
BACKGROUND
We conducted a nationwide study in the Netherlands to determine clinical features and prognostic factors in adults with community-acquired acute bacterial meningitis.
METHODS
From October 1998 to April 2002, all Dutch patients with community-acquired acute bacterial meningitis, confirmed by cerebrospinal fluid cultures, were prospectively evaluated. All patients underwent a neurologic examination on admission and at discharge, and outcomes were classified as unfavorable (defined by a Glasgow Outcome Scale score of 1 to 4 points at discharge) or favorable (a score of 5). Predictors of an unfavorable outcome were identified through logistic-regression analysis.
RESULTS
We evaluated 696 episodes of community-acquired acute bacterial meningitis. The most common pathogens were Streptococcus pneumoniae (51 percent of episodes) and Neisseria meningitidis (37 percent). The classic triad of fever, neck stiffness, and a change in mental status was present in only 44 percent of episodes; however, 95 percent had at least two of the four symptoms of headache, fever, neck stiffness, and altered mental status. On admission, 14 percent of patients were comatose and 33 percent had focal neurologic abnormalities. The overall mortality rate was 21 percent. The mortality rate was higher among patients with pneumococcal meningitis than among those with meningococcal meningitis (30 percent vs. 7 percent, P<0.001). The outcome was unfavorable in 34 percent of episodes. Risk factors for an unfavorable outcome were advanced age, presence of otitis or sinusitis, absence of rash, a low score on the Glasgow Coma Scale on admission, tachycardia, a positive blood culture, an elevated erythrocyte sedimentation rate, thrombocytopenia, and a low cerebrospinal fluid white-cell count.
CONCLUSIONS
In adults presenting with community-acquired acute bacterial meningitis, the sensitivity of the classic triad of fever, neck stiffness, and altered mental status is low, but almost all present with at least two of the four symptoms of headache, fever, neck stiffness, and altered mental status. The mortality associated with bacterial meningitis remains high, and the strongest risk factors for an unfavorable outcome are those that are indicative of systemic compromise, a low level of consciousness, and infection with S. pneumoniae.
Topics: Acute Disease; Adult; Community-Acquired Infections; Consciousness Disorders; Female; Fever; Haemophilus influenzae; Headache; Humans; Male; Meningitis, Bacterial; Middle Aged; Multivariate Analysis; Neck; Neisseria meningitidis; Netherlands; Prognosis; Prospective Studies; Risk Factors; Staphylococcus; Streptococcus; Streptococcus pneumoniae
PubMed: 15509818
DOI: 10.1056/NEJMoa040845 -
The New England Journal of Medicine Nov 2002Mortality and morbidity rates are high among adults with acute bacterial meningitis, especially those with pneumococcal meningitis. In studies of bacterial meningitis in... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Mortality and morbidity rates are high among adults with acute bacterial meningitis, especially those with pneumococcal meningitis. In studies of bacterial meningitis in animals, adjuvant treatment with corticosteroids has beneficial effects.
METHODS
We conducted a prospective, randomized, double-blind, multicenter trial of adjuvant treatment with dexamethasone, as compared with placebo, in adults with acute bacterial meningitis. Dexamethasone (10 mg) or placebo was administered 15 to 20 minutes before or with the first dose of antibiotic and was given every 6 hours for four days. The primary outcome measure was the score on the Glasgow Outcome Scale at eight weeks (a score of 5, indicating a favorable outcome, vs. a score of 1 to 4, indicating an unfavorable outcome). A subgroup analysis according to the causative organism was performed. Analyses were performed on an intention-to-treat basis.
RESULTS
A total of 301 patients were randomly assigned to a treatment group: 157 to the dexamethasone group and 144 to the placebo group. The base-line characteristics of the two groups were similar. Treatment with dexamethasone was associated with a reduction in the risk of an unfavorable outcome (relative risk, 0.59; 95 percent confidence interval, 0.37 to 0.94; P=0.03). Treatment with dexamethasone was also associated with a reduction in mortality (relative risk of death, 0.48; 95 percent confidence interval, 0.24 to 0.96; P=0.04). Among the patients with pneumococcal meningitis, there were unfavorable outcomes in 26 percent of the dexamethasone group, as compared with 52 percent of the placebo group (relative risk, 0.50; 95 percent confidence interval, 0.30 to 0.83; P=0.006). Gastrointestinal bleeding occurred in two patients in the dexamethasone group and in five patients in the placebo group.
CONCLUSIONS
Early treatment with dexamethasone improves the outcome in adults with acute bacterial meningitis and does not increase the risk of gastrointestinal bleeding.
Topics: Acute Disease; Adult; Anti-Bacterial Agents; Chemotherapy, Adjuvant; Dexamethasone; Double-Blind Method; Female; Gastrointestinal Hemorrhage; Glucocorticoids; Humans; Male; Meningitis, Bacterial; Meningitis, Meningococcal; Meningitis, Pneumococcal; Middle Aged; Prospective Studies; Treatment Outcome
PubMed: 12432041
DOI: 10.1056/NEJMoa021334 -
Neurologia Mar 2019The classic clinical presentation of bacterial meningitis (BM) is observed in less than half of the cases in adults, and symptoms are less specific in children, the... (Review)
Review
INTRODUCTION
The classic clinical presentation of bacterial meningitis (BM) is observed in less than half of the cases in adults, and symptoms are less specific in children, the elderly or immunocompromised, and other chronic patients. The usual signs and symptoms do not provide optimal sensitivity and specificity for distinguishing possible BM from viral meningitis (VM), which may lead to a delay in the appropriate antimicrobial therapy. Society therefore stands to benefit from the development of effective, objective, and rapid tools able to predict and identify patients with BM. These tools include laboratory tests for blood and cerebrospinal fluid (CSF). The aim of this review is to summarise recently published scientific evidence in order to clarify existing controversies and compare the usefulness and diagnostic ability of the different parameters used to predict BM.
DEVELOPMENT
Systematic search of the main bibliographic databases and platforms to identify articles published between January 2000 and January 2016. We selected 59 articles that meet the objectives of this review.
CONCLUSIONS
CSF lactate, proportion of polymorphonuclear leukocytes, and CSF glucose, as well as serum procalcitonin (PCT), are the independent factors most predictive of bacterial aetiology. The model that combines serum PCT and CSF lactate achieves the highest predictive power for BM, with a sensitivity and specificity exceeding 99%. We should consider BM when CSF lactate >33 md/dL and/or PCT>0.25ng/mL.
Topics: Biomarkers; Blood Chemical Analysis; Diagnosis, Differential; Emergency Service, Hospital; Humans; Meningitis, Bacterial; Meningitis, Viral
PubMed: 27469578
DOI: 10.1016/j.nrl.2016.05.009