Community-acquired acute bacterial meningitis in adults: a clinical update

Ellis, Jayne; Luintel, Akish; Chandna, Arjun; Heyderman, Robert S

doi:10.1093/bmb/ldz023

Cited by 12Bacterial Infections and VaccinesBacterial Identification and Susceptibility TestingInfectious Diseases and Tuberculosis

Community-acquired acute bacterial meningitis in adults: a clinical update

Ellis, Jayne, Luintel, Akish, Chandna, Arjun, Heyderman, Robert S·2019·British Medical Bulletin

DOI 10.1093/bmb/ldz023

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Abstract

BACKGROUND: Acute bacterial meningitis (ABM) in adults is associated with a mortality that may exceed 30%. Immunization programs have reduced the global burden; in the UK, declining incidence but persistently high mortality and morbidity mean that clinicians must remain vigilant. SOURCES OF DATA: A systematic electronic literature search of PubMed was performed to identify all ABM literature published within the past 5 years. AREAS OF AGREEMENT AND CONTROVERSY: Clinical features cannot reliably distinguish between ABM and other important infectious and non-infectious aetiologies. Prompt investigation and empirical treatment are imperative. Lumbar puncture (LP) and cerebrospinal fluid microscopy, biochemistry and culture remain the mainstay of diagnosis, but molecular techniques are increasingly useful. The 2016 UK joint specialist societies' guideline provides expert recommendations for the management of ABM, yet published data suggest clinical care delivered in the UK is frequently not adherent. Anxiety regarding risk of cerebral herniation following LP, unnecessary neuroimaging, underutilization of molecular diagnostics and suboptimal uptake of adjunctive corticosteroids compromise management. GROWING POINTS: There is increasing recognition that current antibiotic regimens and adjunctive therapies alone are insufficient to reduce the mortality and morbidity associated with ABM. AREAS TIMELY FOR DEVELOPING RESEARCH: Research should be focused on optimization of vaccines (e.g. pneumococcal conjugate vaccines with extended serotype coverage), targeting groups at risk for disease and reservoirs for transmission; improving adherence to management guidelines; development of new faster, more accurate diagnostic platforms (e.g. novel point-of-care molecular diagnostics); and development of new adjunctive therapies (aimed at the host-inflammatory response and bacterial virulence factors).

Integrity signals

Registry

Crossref · 10.1093/bmb/ldz023

Cites

62 of 62 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

37 of 82 cited sources checked · 12 supported · 1 flagged · accuracy not yet measured

Premisecitation
The presence of two or more of headache, neck stiffness, fever and altered consciousness has a sensitivity of 95% for ABM.
“The presence of two or more of headache, neck stiffness, fever and altered consciousness, has a sensitivity of 95% for ABM. 4”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [4] Beek, 2004, Clinical features and prognostic factors in adults with bacterial meningitis, N Engl J Med source
  The Results (p. 2) report that 95% of 696 episodes had at least two of the four symptoms, supporting the stated sensitivity within the study population. The study covered adults with community-acquired acute bacterial meningitis; the claim states 95% for ABM without that limitation. (LLM, conf=0.83)
  Experimental — accuracy not yet measured
Premisecitation
A rise in nonvaccine pneumococcal serotypes has to some extent offset the benefits of vaccine introduction.
“Indeed, a rise in nonvaccine serotypes has to some extent offset the benefits of vaccine introduction 9”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [9] Feikin, 2013, Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites, PLoS Med source
Premisecitation
Enterobacteriaceae such as E. coli and rarely Listeria monocytogenes, Haemophilus influenzae, Streptococcus agalactiae, Staphylococcus aureus are associated with mortality estimates ranging from 30% to 60%.
“These include Enterobacteriaceae such as E. coli and rarely Listeria monocytogenes, Haemophilus influenzae, Streptococcus agalactiae, Staphylococcus aureus, 22 which are associated with mortality estimates ranging from 30% to 60%.7,22,23”
Quote in the paperNot a substantial claim3 of 3 sources checked
- cites [7] Pomar, 2013, Spontaneous gram-negative bacillary meningitis in adult patients: characteristics and outcome, BMC Infect Dis source
  The Results (Outcome; page unavailable) report 53% mortality in adults with spontaneous gram-negative bacillary meningitis, and the Discussion identifies E. coli as its most common cause. The Discussion gives a 40%–60% range from previous reports, not 30%–60%; it does not establish that range for the other listed pathogens. (LLM, conf=0.88)
  Experimental — accuracy not yet measured
- cites [22] Domingo, 2013, The spectrum of acute bacterial meningitis in elderly patients, BMC Infect Dis source
  The Results (CSF findings, microbiologic features and etiology) identify all the named organisms among the meningitis cases. But Listeria was more frequent in elderly patients, not described as rare, and the Results (Evolving features and outcome) give mortality of 0% for elderly patients with H. influenzae meningitis and 31.0% for the combined listerial/gram-positive-bacilli category. The claimed 30%–60% range therefore does not hold for every organism listed. (LLM, conf=0.89)
  Experimental — accuracy not yet measured
- cites [23] Koopmans, 2017, Listeria monocytogenes meningitis in the Netherlands, 1985–2014: a nationwide surveillance study, J Infect source
  The Results report a 31% case-fatality rate for Listeria meningitis, supporting the lower end of the stated mortality range for that pathogen. The cited passages do not establish 30%–60% mortality for the other listed organisms, and the Background’s 61% figure concerns unfavorable outcomes, not mortality. Page numbers were not supplied. (LLM, conf=0.88)
  Experimental — accuracy not yet measured
Premisecitation
Characteristic features such as neck stiffness and headache are less frequent in the elderly, particularly those with Gram-negative bacillary meningitis.
“Characteristic features such as neck stiffness and headache are less frequent in the elderly, particularly those with Gram-negative bacillary meningitis (GNBM).7”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [7] Pomar, 2013, Spontaneous gram-negative bacillary meningitis in adult patients: characteristics and outcome, BMC Infect Dis source
  The Results (Characteristics of spontaneous GNBM; page not provided) report that patients with GNBM were older and had less frequent neck stiffness and headache than patients with meningitis from other causes. The paper does not establish that these symptoms are less frequent in elderly patients generally, or compare symptom frequency by age. (LLM, conf=0.86)
  Experimental — accuracy not yet measured
Premisecitation
Disease also occurs following direct bacterial translocation from the upper respiratory tract to the meninges through the cribriform plate.
“Disease also occurs following direct bacterial translocation from the upper respiratory tract to the meninges through the cribriform plate. 1”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [1] McGill, 2016, Acute bacterial meningitis in adults, Lancet source
  The Invasion section says direct spread from respiratory infection to the central nervous system may occur and that entry from the nose through dural defects is possible. It does not identify the cribriform plate as the route, and it presents direct spread as a possibility rather than an established occurrence. No page number is available in our copy. (LLM, conf=0.88)
  Experimental — accuracy not yet measured

Premisecitation
CNS inflammation and disruption of the BBB results in CNS tissue damage through apoptotic neuronal injury, oedema, microvascular thrombosis and raised intracranial pressure.
“CNS inflammation and disruption of the BBB results in CNS tissue damage through apoptotic neuronal injury, oedema, microvascular thrombosis and raised intracranial pressure.26”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [26] Doran, 2016, Host–pathogen interactions in bacterial meningitis, Acta Neuropathol source
Premisecitation
Most other causes of community-acquired ABM in adults occur in those with particular risk factors for immune compromise or immunosenescence such as alcohol dependency, pregnancy, diabetes mellitus, patients taking immunosuppressive medications and old age.
“Most other causes of community-acquired ABM in adults occur in those with particular risk factors for immune compromise or immunosenescence such as alcohol dependency, pregnancy, diabetes mellitus, patients taking immunosuppressive medications and old age.7”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [7] Pomar, 2013, Spontaneous gram-negative bacillary meningitis in adult patients: characteristics and outcome, BMC Infect Dis source
  The Discussion (page unavailable) says spontaneous gram-negative bacillary meningitis occurs most frequently in older adults with conditions including alcoholism, diabetes and causes of immunosuppression. It does not establish that most other causes of community-acquired acute bacterial meningitis follow this pattern, or identify pregnancy or immunosuppressive medications specifically as risk factors. (LLM, conf=0.86)
  Experimental — accuracy not yet measured
Premisecitation
Bloodstream invasion allows bacteria to reach and cross the BBB, either transcellularly or paracellularly, to the CNS.
“Bloodstream invasion allows bacteria to reach and then cross the BBB, either transcellularly or paracellularly to the CNS. 1”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [1] McGill, 2016, Acute bacterial meningitis in adults, Lancet source
  The Pathogenesis and Invasion sections describe bloodstream invasion followed by entry into the subarachnoid space, and say most cases probably follow bacteraemia. But Invasion applies transcellular and between-cell routes to entry into the bloodstream, not to bacterial crossing of the blood–brain barrier; the CNS-entry section does not establish those routes across the BBB. No page numbers were supplied. (LLM, conf=0.88)
  Experimental — accuracy not yet measured
Premisecitation
In a recent multi-centre prospective cohort study of adults with suspected meningitis in 42 UK hospitals, the median time to LP was 17 h (IQR 8-29).
“In a recent multi-centre prospective cohort study of adults with suspected meningitis in 42 UK hospitals, the median time to LP was 17 h (IQR 8-29).37”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [37] McGill, 2018, Incidence, aetiology, and sequelae of viral meningitis in UK adults: a multicentre prospective observational cohort study, Lancet Infect Dis source
Premisecitation
CSF microscopy, biochemistry and culture to confirm aetiology and antimicrobial susceptibility of causative pathogens remain the mainstay of diagnosis.
“CSF microscopy, biochemistry and culture to confirm aetiology and antimicrobial susceptibility of causative pathogens remain the mainstay of diagnosis.32”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [32] McGill, 2016, The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults, J Infect source
Premisecitation
Suboptimal use of molecular diagnostics and HIV-testing has been highlighted as areas for improvement.
“Suboptimal use of molecular diagnostics and HIV-testing has also been highlighted as areas for improvement.39,[59][60][61]”
Quote in the paperNot a substantial claim1 of 3 sources checked
- cites [39] Costerus, 2018, Cranial computed tomography, lumbar puncture, and clinical deterioration in bacterial meningitis: a nationwide cohort study, Clin Infect Dis source
- cites [59] Stockdale, 2011, An audit of acute bacterial meningitis in a large teaching hospital 2005–10, QJM source
  The Microbiology section reports that blood PCR was used in only 11 of 39 patients (28%), and the Discussion highlights PCR’s utility in diagnosing culture-negative meningitis. This supports concern about limited use of molecular diagnostics, but our copy does not address HIV testing as an area for improvement (searched: HIV, HIV testing). (LLM, conf=0.85)
  Experimental — accuracy not yet measured
- cites [60] Proulx, 2005, Delays in the administration of antibiotics are associated with mortality from adult acute bacterial meningitis, QJM source
Premisecitation
If blood cultures are taken prior to antibiotic administration, the yield can be as high as 74%.
“If taken prior to antibiotic administration, the yield can be as high as 74%.30”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [30] Granier, 1998, Recognising meningococcal disease in primary care: qualitative study of how general practitioners process clinical and contextual information, BMJ source
  The Subjects and methods section mentions blood cultures but gives no yield by timing of antibiotic administration. A search for “74% blood culture positivity” found 74% only in a table of illness duration in the Puzzling findings section, not as a culture yield; the claim is not addressed in our copy. Page numbers were unavailable. (LLM, conf=0.76)
  Experimental — accuracy not yet measured
Premisecitation
Rifampicin has shown promise as a potential adjunct in human studies.
“has also shown promise as a potential adjunct in human studies.55,56”
Quote in the paperNot a substantial claim1 of 2 sources checked
- cites [55] Hupp, 2017, Magnesium therapy improves outcome in Streptococcus pneumoniae meningitis by altering pneumolysin pore formation, Br J Pharmacol source
  The Discussion proposes magnesium as an adjunct and recommends a future clinical study; it does not report human studies of rifampicin. Searches for “rifampicin” and “rifampin” found rifampin only in reference titles concerning experimental or infant-rat meningitis, not evidence for the attributed human-study claim. (LLM, conf=0.76)
  Experimental — accuracy not yet measured
- cites [56] Paladino, 2010, Outpatient parenteral antimicrobial therapy today, Clin Infect Dis source
Premisecitation
A Dutch multi-centre trial of adult ABM showed reduction in mortality particularly in pneumococcal meningitis.
“A Dutch multi-centre trial of adult ABM showed reduction in mortality particularly in pneumococcal meningitis.51”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [51] Brouwer, 2015, Corticosteroids for acute bacterial meningitis, Cochrane Database Syst Rev source
Premisecitation
Rifampicin has significant anti-inflammatory properties.
“Rifampicin although bacteriostatic has significant anti-inflammatory properties”
Quote in the paperNot a substantial claim1 of 2 sources checked
- cites [55] Hupp, 2017, Magnesium therapy improves outcome in Streptococcus pneumoniae meningitis by altering pneumolysin pore formation, Br J Pharmacol source
  The Introduction (page unavailable) discusses reduced release of neurotoxic factors with non-bacteriolytic antibiotics, but does not identify rifampicin as having anti-inflammatory properties. Searches for “rifampicin anti-inflammatory,” “rifampin,” and “anti-inflammatory” found rifampin only in reference titles, not a statement supporting the claim. (LLM, conf=0.76)
  Experimental — accuracy not yet measured
- cites [56] Paladino, 2010, Outpatient parenteral antimicrobial therapy today, Clin Infect Dis source
Premisecitation
Serum procalcitonin measurement has been reported to have a sensitivity of ∼95% and a specificity of ∼100% in distinguishing bacterial from viral meningitis in adults.
“The use of serum procalcitonin measurement remains limited due to cost but where available has been reported to have a sensitivity of ∼95% and a specificity of ∼100% in distinguishing bacterial from viral meningitis in adults.45”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [45] Morales Casado, 2016, Capacidad de la procalcitonina para predecir meningitis bacterianas en el servicio de urgencias, Neurologia source
Premisecitation
Delayed LPs are associated with increased mortality in ABM.
“Delayed LPs in particular have been shown to be associated with increased mortality in ABM.62”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [62] Seki, 2018, Loop-mediated isothermal amplification methods for diagnosis of bacterial meningitis, Front Pediatr source
  The Introduction says that prompt identification and CSF analysis are important for bacterial meningitis, but it does not discuss delayed lumbar puncture or its association with mortality. Searches for delayed lumbar puncture, LP, and mortality found no passage addressing that association. (LLM, conf=0.76)
  Experimental — accuracy not yet measured
Premisecitation
CSF opening pressure is usually raised (>20 cm H2O) in ABM.
“CSF opening pressure should be measured (unless LP is performed in seated position, which artificially raises the opening pressure) and is usually raised (>20 cm H20) in ABM. 4”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [4] Beek, 2004, Clinical features and prognostic factors in adults with bacterial meningitis, N Engl J Med source
  The results (p. 6) report that opening pressure was normal—below 200 mm of water, or 20 cm H₂O—in only 18% of the 216 episodes evaluated. This supports the claim that pressure is usually raised in adult bacterial meningitis. The cited paper does not address the sentence’s advice to measure opening pressure or its exception for a seated lumbar puncture. (LLM, conf=0.86)
  Experimental — accuracy not yet measured
Premisecitation
Several potential targets and interventions have been tested in animal models and small retrospective human studies.
“Although several potential targets and interventions have been tested in animal models 57 and small retrospective human studies 55”
Quote in the paperNot a substantial claim1 of 2 sources checked
- cites [57] Cullen, 2005, An audit of the investigation and initial management of adults presenting with possible bacterial meningitis, J Infect source
- cites [55] Hupp, 2017, Magnesium therapy improves outcome in Streptococcus pneumoniae meningitis by altering pneumolysin pore formation, Br J Pharmacol source
Premisecitation
Bacterial components trigger microglia and phagocytic cells to release pro-inflammatory mediators such as TNF, IL-6 and IL-1B.
“Bacterial components trigger microglia and phagocytic cells to release pro-inflammatory mediators 25 such as TNF, IL-6 and IL-1B.”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [25] Sheu, 2013, Resveratrol suppresses calcium-mediated microglial activation and rescues hippocampal neurons of adult rats following acute bacterial meningitis, Comp Immunol Microbiol Infect Dis source
Premisecitation
Reductions in incidence of >97% were seen within a decade after MenC vaccination.
“Reductions in incidence of >97% were seen within a decade.12”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [12] Campbell, 2009, Meningococcal C conjugate vaccine: the experience in England and Wales, Vaccine source
Premisecitation
Even when optimal management is delivered, mortality from acute bacterial meningitis has changed little in the past 20 years.
“Nonetheless, even when optimal management is delivered, mortality has changed little in the past 20 years.[2][3][4]”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [2][3][4]
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Interpretationreasoning
There is insufficient evidence to recommend adjunctive doxycycline, rifampicin, or magnesium in routine clinical care due to a lack of human clinical trial data.
“To date, however, there is a lack of clinical trial data in humans and therefore insufficient evidence to recommend these interventions in routine clinical care.”
Quote in the paperSubstantial claim
Premisecitation
Close contacts have an increased risk of IMD for 6 months following exposure.
“Close contacts have an increased risk of IMD for 6 months following exposure”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [34] Kaplan, 2017, Acute bacterial meningitis caused by acute otitis media in adults: a series of 12 patients, Ear Nose Throat J
Premisecitation
Despite widely available national guidelines on meningitis case management, published data suggest that clinical care delivered in the UK remains suboptimal.
“Despite the existence of widely available national guidelines on meningitis case management, 34 published data suggest that the clinical care delivered in the UK remains suboptimal.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [34] Kaplan, 2017, Acute bacterial meningitis caused by acute otitis media in adults: a series of 12 patients, Ear Nose Throat J
Premisecitation
Adjunctive magnesium was associated with improved survival in mice with pneumococcal meningitis.
“was associated with improved survival in mice with pneumococcal meningitis.57”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [57] Cullen, 2005, An audit of the investigation and initial management of adults presenting with possible bacterial meningitis, J Infect source
Premisecitation
Secondary cases of IMD are estimated to occur in 2-4 per 1000 cases of close contacts.
“Secondary cases of IMD are estimated to occur in 2-4 per 1 000 cases of close contacts.34”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [34] Kaplan, 2017, Acute bacterial meningitis caused by acute otitis media in adults: a series of 12 patients, Ear Nose Throat J
Premisecitation
Altered mental status occurs less frequently in nosocomial meningitis than in community-acquired ABM.
“Altered mental status occurs less frequently than in community-acquired ABM. 36”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [36] Kumari, 2015, Methicillin-resistant Staphylococcus aureus central nervous system infections—analysis and outcome, Br J Neurosurg source
Premisecitation
A meta-analysis of all-cause ABM in children demonstrated non-inferiority between 4 and 7 and 7 and 14 days of treatment.
“A metaanalysis of all-cause ABM in children demonstrated non-inferiority between 4 and 7 and 7 and 14 days of treatment.46”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [46] Karageorgopoulos, 2009, Short versus long duration of antibiotic therapy for bacterial meningitis: a meta-analysis of randomised controlled trials in children, Arch Dis Child source
Premisecitation
In the majority of cases, nasopharyngeal meningococcal isolates from patients with suspected ABM are almost always identical to those from their blood or CSF.
“This is because in the majority of cases, nasopharyngeal meningococcal isolates from patients with suspected ABM are almost always identical to those from their blood or CSF.34”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [34] Kaplan, 2017, Acute bacterial meningitis caused by acute otitis media in adults: a series of 12 patients, Ear Nose Throat J
Premisecitation
A study on IMD showed 3 days of benzylpenicillin treatment was sufficient.
“A study on IMD showed 3 days of benzylpenicillin treatment was sufficient.47”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [47] Ellis-Pegler, 2003, Three days of intravenous benzyl penicillin treatment of meningococcal disease in adults, Clin Infect Dis source
Premisecitation
Most patients with meningococcal meningitis have become colonized with the causative bacteria in the preceding 7 days.
“Most patients with meningococcal meningitis have become colonized with the causative bacteria in the preceding 7 days”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [34] Kaplan, 2017, Acute bacterial meningitis caused by acute otitis media in adults: a series of 12 patients, Ear Nose Throat J
Premisecitation
Adjunctive magnesium targets pneumococcal pneumolysin-driven neuronal injury.
“Adjunctive magnesium, which targets pneumococcal pneumolysin-driven neuronal injury”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [57] Cullen, 2005, An audit of the investigation and initial management of adults presenting with possible bacterial meningitis, J Infect source
Interpretationnone given
Inappropriate neuroimaging leads to delays in LP and antibiotic administration.
“Inappropriate neuroimaging leads to delays in LP and antibiotic administration.”
Quote in the paperNot a substantial claim
Premisecitation
There is little evidence that LP and complications are causally related.
“there is little evidence that the two are causally related.41”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [41] Huang, 2004, Supratentorial cerebrospinal fluid production rate in healthy adults: quantification with two-dimensional cine phase-contrast MR imaging with high temporal and spatial resolution, Radiology source
Premisecitation
Physicians' fear of cerebral herniation following LP is an important factor leading to unnecessary neuroimaging.
“Physicians' fear of cerebral herniation following LP, leading to unnecessary neuroimaging, is also an important factor.63”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [63] Guo, 2018, Next-generation sequencing could be a promising diagnostic approach for pathogen detection: pathogenic analysis of pediatric bacterial meningitis by next-generation sequencing technology directly from crebrospinal fluid specimens source
Interpretationcitation
Expanded use of whole genome sequencing has the greatest potential to transform meningitis diagnostics, particularly prediction of genotypic drug resistance.
“it is the expanded use of whole genome sequencing in clinical care as it becomes increasingly rapid, accessible, affordable and directly applicable to clinical specimens without the need for culture that has the greatest potential to transform meningitis diagnostics, particularly prediction of genotypic drug resistance 63”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [63] Guo, 2018, Next-generation sequencing could be a promising diagnostic approach for pathogen detection: pathogenic analysis of pediatric bacterial meningitis by next-generation sequencing technology directly from crebrospinal fluid specimens source
Premisecitation
In McGill et al. (2018), aetiology was unknown in 42% of cases.
“In the report from McGill et al. (2018) the aetiology was unknown in 42% of cases.39”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [39] Costerus, 2018, Cranial computed tomography, lumbar puncture, and clinical deterioration in bacterial meningitis: a nationwide cohort study, Clin Infect Dis source
Premisecitation
Complications following LP in ABM are extremely rare.
“Several studies demonstrate that complications following LP in ABM are extremely rare”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [41] Huang, 2004, Supratentorial cerebrospinal fluid production rate in healthy adults: quantification with two-dimensional cine phase-contrast MR imaging with high temporal and spatial resolution, Radiology source

May combine two claims. 29
Classified as probably not a substantial claim. 13

May combine two claims.
Premisecitation
ABM incidence in England and Wales has remained stable over the past decade, with falling pneumococcal and meningococcal cases offset by a rise in Gram-negative Enterobacteriaceae, particularly in those aged >65 years.
“This incidence has remained stable over the past decade with falling numbers of pneumococcal and meningococcal meningitis cases offset by a rise in ABM due to Gram-negative Enterobacteriaceae, such as Escherichia coli and Klebsiella pneumoniae, particularly in those aged >65 years.5,7”
Quote in the paperNot a substantial claim1 of 2 sources checked
- cites [5] Okike, 2014, Trends in bacterial, mycobacterial, and fungal meningitis in England and Wales 2004–11: an observational study, Lancet Infect Dis source
- cites [7] Pomar, 2013, Spontaneous gram-negative bacillary meningitis in adult patients: characteristics and outcome, BMC Infect Dis source
  The Results and Conclusion report that the proportion of spontaneous gram-negative bacillary meningitis did not increase over the study period; the Discussion attributes increases reported elsewhere mainly to post-neurosurgical cases. The paper finds that affected patients tend to be older and that E. coli is a common cause, but it does not report the claimed offsetting trends in England and Wales. (LLM, conf=0.82)
  Checked by a reasoning model — may be wrong.
  Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation
The case-fatality ratio for pneumococcal meningitis has been estimated to be 30%.
“The case-fatality ratio for pneumococcal meningitis has been estimated to be 30%.4”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [4] Beek, 2004, Clinical features and prognostic factors in adults with bacterial meningitis, N Engl J Med source
May combine two claims.
Premisecitation
Presenting features of ABM in adults vary according to patient age and cannot reliably distinguish bacterial from viral meningitis or other differential diagnoses.
“Presenting features of ABM in adults vary according to patient age 28 and cannot reliably distinguish bacterial from viral meningitis or other differential diagnoses.29”
Quote in the paperSubstantial claim1 of 2 sources checked
- cites [28] Magazzini, 2012, Clinical picture of meningitis in the adult patient and its relationship with age, Intern Emerg Med source
- cites [29] Khatib, 2017, Adults with suspected central nervous system infection: a prospective study of diagnostic accuracy, J Infect source
May combine two claims.
Premisecitation
The most consistent clinical symptom in ABM is headache; however, no individual symptom can satisfactorily discriminate ABM from other conditions.
“The most consistent clinical symptom in ABM is headache; 4 however, no individual symptom can satisfactorily discriminate ABM from other conditions.30”
Quote in the paperNot a substantial claim2 of 2 sources checked
- cites [4] Beek, 2004, Clinical features and prognostic factors in adults with bacterial meningitis, N Engl J Med source
  Citation 30 is attached to the claim about distinguishing ABM from other conditions. The Results (p. 4) report symptom frequencies among patients with bacterial meningitis, and the Conclusions (p. 2) discuss the low sensitivity of the classic triad, but neither assesses how well an individual symptom distinguishes ABM from other conditions. The headache claim is attached to citation 4, not this citation. (LLM, conf=0.76)
  Experimental — accuracy not yet measured
- cites [30] Granier, 1998, Recognising meningococcal disease in primary care: qualitative study of how general practitioners process clinical and contextual information, BMJ source
  The Introduction says that signs and symptoms of meningococcal disease are often non-specific in primary care, making diagnosis difficult. The Discussion describes widely varying combinations of symptoms in children. These passages support the general diagnostic difficulty, but the paper does not establish that no individual symptom can discriminate acute bacterial meningitis from other conditions. The headache clause is attached to a different citation and is not judged here. (LLM, conf=0.78)
  Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation
Prompt recognition, appropriate investigation and treatment save lives in acute bacterial meningitis.
“It is widely acknowledged that prompt recognition, appropriate investigation and treatment save lives. 1”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [1] McGill, 2016, Acute bacterial meningitis in adults, Lancet source
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation
The incidence of invasive MenY disease has been increasing in Sweden, Canada and the US.
“The incidence of invasive MenY disease has been increasing in Sweden, Canada and the US.19”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [19] Säll, 2017, Clinical presentation of invasive disease caused by Neisseria meningitidis serogroup Y in Sweden, 1995 to 2012, Epidemiol Infect source
  The Abstract states that invasive MenY incidence increased significantly in Sweden from 1995 to 2012. The Introduction reports an increased proportion of MenY cases in the USA, but does not establish an increased incidence there; it does not mention Canada in its account of countries with increases. (LLM, conf=0.88)
  Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation
A 56% reduction in invasive pneumococcal disease among adults has been reported since the introduction of PCV7 into the routine infant schedule and its replacement by PCV13 in April 2010.
“A 56% reduction in invasive pneumococcal disease (IPD) among adults has been reported since the introduction of the PCV7 into the routine infant schedule and its replacement by PCV13 in April 2010.8”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [8] Waight, 2015, Effect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction: an observational cohort study, Lancet Infect Dis source
  The Figure 1 and table section reports a 56% reduction in overall invasive pneumococcal disease in England and Wales in 2013/14 compared with the pre-PCV7 baseline. The Introduction confirms that PCV13 replaced PCV7 in April 2010. The 56% figure, however, covers all ages, not adults specifically. (LLM, conf=0.90)
  Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation
For all serogroups, outbreaks of meningococcal meningitis are associated with higher case-fatality ratios than sporadic cases.
“For all serogroups, outbreaks of meningococcal meningitis are associated with higher case-fatality ratios than sporadic cases.21”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [21] Brooks, 2006, Increased case-fatality rate associated with outbreaks of Neisseria meningitidis infection, compared with sporadic meningococcal disease, in the United States, 1994–2002, Clin Infect Dis source
  Results (Table 3; page not provided) show higher observed case-fatality rates for outbreak-associated than sporadic cases in serogroups C, B, and Y. But the differences for B and Y are statistically uncertain, there were no outbreak-associated W-135 cases, and the meningitis-specific comparison (13% vs. 10%) is also uncertain. The claim overstates the evidence by saying this holds for all serogroups of meningococcal meningitis. (LLM, conf=0.87)
  Experimental — accuracy not yet measured
May combine two claims.
Premisecitation
The 2015 Cochrane review showed severe hearing loss was significantly reduced by corticosteroids; this was especially true in high-income countries.
“The 2015 Cochrane review showed severe hearing loss was significantly reduced by corticosteroids; this was especially true in high-income countries.”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [53] Bretonnière, 2015, Rifampin use in acute community-acquired meningitis in intensive care units: the French retrospective cohort ACAM-ICU study, Crit Care source
  Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.
  Experimental — accuracy not yet measured
May combine two claims.
Premisecitation
CSF microscopy and Gram staining for bacteria has a sensitivity of 50-99% (dependent on organism and prior antibiotics) and a specificity of 97-100% in the diagnosis of ABM.
“CSF microscopy and Gram staining for bacteria has a sensitivity of 50-99% (dependent on organism and prior antibiotics) and a specificity of 97-100% in the diagnosis of ABM. 4”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [4] Beek, 2004, Clinical features and prognostic factors in adults with bacterial meningitis, N Engl J Med source
  The results (p. 6) report 80% sensitivity and 97% specificity for CSF Gram staining, values within the claimed ranges, but do not establish the full ranges. They also say the yield was similar with and without prior antimicrobial therapy, rather than showing the claimed dependence on prior antibiotics. (LLM, conf=0.88)
  Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation
Numerous adjunctive interventions have shown promise in tissue culture and animal models.
“Numerous adjunctive interventions have shown promise in tissue culture and animal models.29”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [29] Khatib, 2017, Adults with suspected central nervous system infection: a prospective study of diagnostic accuracy, J Infect source
  The Introduction describes a study of diagnostic accuracy in adults with suspected CNS infection, while the Results report clinical investigations and treatments. Searches for adjunctive interventions and for experimental animal or tissue-culture models found no passage addressing whether such interventions showed promise. (LLM, conf=0.76)
  Experimental — accuracy not yet measured
May combine two claims.
Premisecitation
Delayed LPs led to a reduction in pathogen detection, increased exposure to unnecessary anti-infectives and prolonged hospital stay.
“Delayed LPs led to a reduction in pathogen detection, increased exposure to unnecessary anti-infectives and prolonged hospital stay.37”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [37] McGill, 2018, Incidence, aetiology, and sequelae of viral meningitis in UK adults: a multicentre prospective observational cohort study, Lancet Infect Dis source
  The Results report that each hour of delayed lumbar puncture was associated with a 1% lower chance of pathogen detection in viral meningitis. The Discussion links a specific diagnosis to less inappropriate treatment and shorter stays, while the Abstract’s Interpretation says delayed punctures and unnecessary antivirals were associated with longer stays. The claim overstates these observational findings by saying delayed punctures caused all three outcomes. (LLM, conf=0.86)
  Experimental — accuracy not yet measured
May combine two claims.
Premisecitation
In most cases of ABM neuroimaging is not indicated prior to LP and can result in delays to antibiotic therapy and increased mortality.
“In most cases of ABM neuroimaging is not indicated prior to LP and can result in delays to antibiotic therapy and increased mortality.32”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [32] McGill, 2016, The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults, J Infect source
May combine two claims.
Premisecitation
Subgroup analysis showed a significant reduction in mortality in S. pneumoniae meningitis but not in N. meningitidis or H. influenzae meningitis.
“Subgroup analysis in this data showed a significant reduction in mortality in S. pneumoniae meningitis but not in N. meningitidis or H. influenzae meningitis.53”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [53] Bretonnière, 2015, Rifampin use in acute community-acquired meningitis in intensive care units: the French retrospective cohort ACAM-ICU study, Crit Care source
  In Results > Rifampin use (page unavailable), Table 2 reports a significant unadjusted association between rifampin given within 24 hours and lower ICU mortality in S. pneumoniae meningitis (p=0.031). It does not report corresponding subgroup analyses for N. meningitidis or H. influenzae. The Discussion also says the multivariate analysis found no association between rifampin use and ICU mortality, so the claim overstates the finding as a reduction in mortality. (LLM, conf=0.88)
  Experimental — accuracy not yet measured
May combine two claims.
Premisecitation
PCR has high sensitivity (87-100%) and specificity (98-100%) for bacterial DNA in CSF.
“PCR has high sensitivity (87-100%) and specificity (98-100%).1”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [1] McGill, 2016, Acute bacterial meningitis in adults, Lancet source
May combine two claims.
Findingown data
In England and Wales, 2013-17, the annual incidence of laboratory-confirmed ABM in adults was low, with S. pneumoniae the most common cause (0.12-0.18 per 100,000).
“Table 1 Incidence per 100 000 people of the main causes of laboratory-confirmed ABM in adults in England and Wales, 2013-17 (data from PHE) *”
Quote in the paperNot a substantial claim
May combine two claims.
Premisecitation
Kernig's and Brudzinski's signs are often cited but their sensitivity can be as low as 5%.
“Kernig's and Brudzinski's signs are often cited but their sensitivity can be as low as 5%.33”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [33] Brouwer, 2012, Dilemmas in the diagnosis of acute community-acquired bacterial meningitis, Lancet source
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation
Today, >75% of IMD in adults in the UK is caused by meningococcus group B (MenB).
“Today, >75% of IMD in adults in the UK is caused by meningococcus group B (MenB), 10”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [10] Ladhani, 2012, Invasive meningococcal disease in England and Wales: implications for the introduction of new vaccines, Vaccine source
May combine two claims.
Premisecitation
The MenB vaccine is anticipated to protect against 73-88% of invasive strains, but ongoing surveillance will be essential to determine true vaccine effectiveness.
“The vaccine is anticipated to protect against 73-88% of invasive strains, but ongoing surveillance will be essential to determine true vaccine effectiveness.16”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [16] Parikh, 2016, Effectiveness and impact of a reduced infant schedule of 4CMenB vaccine against group B meningococcal disease in England: a national observational cohort study, Lancet source
May combine two claims.
Premisecitation
S. pneumoniae is the commonest cause of community-acquired ABM in adults in England and Wales, responsible for 30% of laboratory-confirmed cases.
“S. pneumoniae is the commonest cause of communityacquired ABM in adults in England and Wales, responsible for 30% of laboratory-confirmed cases (PHE data 2017).”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites PHE data 2017
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Premisecitation
S. pneumoniae and N. meningitidis are both highly successful colonizers of the human nasopharynx.
“Streptococcus pneumoniae and N. meningitidis are both highly successful colonizers of the human nasopharynx.24”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [24] Gerber, 2010, Mechanisms of injury in bacterial meningitis, Curr Opin Neurol source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation
N. meningitidis remains the second leading cause of community-acquired ABM in adults in England and Wales, responsible for 10% of laboratory-confirmed cases.
“N. meningitidis remains the second leading cause of community-acquired ABM in adults in England and Wales, responsible for 10% of laboratory-confirmed cases (PHE data 2017).”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites PHE data 2017
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation
The risk of invasive meningococcal disease is highest in infancy, with a second peak between 15 and 19 years (incidence 3.2 per 100 000), reducing to 0.5-0.7 per 100 000 for those >25 years.
“While the risk of invasive meningococcal disease (IMD) is highest in infancy, a second peak occurs between 15 and 19 years with incidence of 3.2 per 100 000, reducing to 0.5-0.7 per 100 000 for those >25 years.10”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [10] Ladhani, 2012, Invasive meningococcal disease in England and Wales: implications for the introduction of new vaccines, Vaccine source
May combine two claims.
Premisecitation
Non-infectious mimics of ABM include subarachnoid haemorrhage, autoimmune syndromes, paraneoplastic syndromes, migraine and rarely medications such as lamotrigine and cotrimoxazole.
“Non-infectious mimics of ABM include subarachnoid haemorrhage, autoimmune syndromes, paraneoplastic syndromes, migraine and rarely medications, such as lamotrigine and cotrimoxazole.35”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [35] Simms, 2012, Lamotrigine and aseptic meningitis, Neurology source
May combine two claims.
Premisecitation
A subsequent meta-analysis investigating corticosteroid use showed no difference in mortality but some improvement in hearing loss.
“A subsequent meta-analysis investigating corticosteroid use showed no difference in mortality but some improvement in hearing loss.52”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [52] Meli, 2006, Doxycycline reduces mortality and injury to the brain and cochlea in experimental pneumococcal meningitis, Infect Immun source
May combine two claims.
Premisecitation
In animal models, doxycycline given as an adjunct alongside ceftriaxone downregulates CSF inflammation, leading to reduced mortality and attenuated hearing loss.
“in animal models, when given as an adjunct alongside ceftriaxone, has been shown to downregulate CSF inflammation leading to reduced mortality and attenuated hearing loss.54”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [54] Uppal, 2017, Role of rifampin in reducing inflammation and neuronal damage in childhood bacterial meningitis, Pediatr Infect Dis J source
- Rests on an assumption: Matrix metalloproteinases (MMPs) are key immune mediators that promote blood-brain barrier disruption and brain injury.
- Rests on an assumption: Doxycycline is an effective MMP inhibitor.
May combine two claims.
Interpretationreasoning
The duration of antibiotics in adults is based largely on expert opinion and is dependent on the organism isolated and clinical response.
“Therefore, the duration of antibiotics in adults is based largely on expert opinion and is dependent on the organism isolated and clinical response (Table 3).”
Quote in the paperSubstantial claim0 of 2 sources checked
- cites [46] Karageorgopoulos, 2009, Short versus long duration of antibiotic therapy for bacterial meningitis: a meta-analysis of randomised controlled trials in children, Arch Dis Child source
- cites [47] Ellis-Pegler, 2003, Three days of intravenous benzyl penicillin treatment of meningococcal disease in adults, Clin Infect Dis source
- Rests on an assumption: There is little evidence to guide duration of antibiotics for ABM outside paediatric trials.
May combine two claims.
Premisecitation
CSF culture positivity rate declines by >30% when LP is performed >4 h after initiation of antibiotics; however, the cell count and biochemistry remain informative up to 24-72 h later.
“CSF culture positivity rate declines by >30% when LP is performed >4 h after initiation of antibiotics; 38 however, the cell count and biochemistry remain informative up to 24-72 h later.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [38] Nigrovic, 2008, Effect of antibiotic pretreatment on cerebrospinal fluid profiles of children with bacterial meningitis, Pediatrics source
May combine two claims.
Premisecitation
Corticosteroids improve outcomes in ABM, due to reduction in inflammation.
“Corticosteroids improve outcomes in ABM, due to reduction in inflammation.34”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [34] Kaplan, 2017, Acute bacterial meningitis caused by acute otitis media in adults: a series of 12 patients, Ear Nose Throat J
  Not checked in the free run.
May combine two claims.
Premisecitation
Benefits of OPAT include reduced costs, shorter inpatient stays, fewer nosocomial infections and increased patient satisfaction.
“Benefits include reduced costs, shorter inpatient stays, fewer nosocomial infections and increased patient satisfaction.58”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [58] Michael, 2010, Effect of delayed lumbar punctures on the diagnosis of acute bacterial meningitis in adults, Emerg Med J source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation
CSF is produced at a rate of 22 ml/h and 15 ml or more can be taken safely.
“CSF is produced at a rate of 22 ml/h and 15 ml or more can be taken safely.38,39”
Quote in the paperNot a substantial claim0 of 2 sources checked
- cites [38] Nigrovic, 2008, Effect of antibiotic pretreatment on cerebrospinal fluid profiles of children with bacterial meningitis, Pediatrics source
- cites [39] Costerus, 2018, Cranial computed tomography, lumbar puncture, and clinical deterioration in bacterial meningitis: a nationwide cohort study, Clin Infect Dis source
Classified as probably not a substantial claim. May combine two claims.
Premisecitation
The recommended empirical regimen in the UK is a third-generation cephalosporin (ceftriaxone or cefotaxime), which has bactericidal activity for both S. pneumoniae and N. meningitidis, while achieving good CNS penetration.
“The recommended empirical regimen in the UK is a third-generation cephalosporin (ceftriaxone or cefotaxime), which has bactericidal activity for both S. pneumoniae and N. meningitidis, while achieving good CNS penetration.24”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [24] Gerber, 2010, Mechanisms of injury in bacterial meningitis, Curr Opin Neurol source
May combine two claims.
Premisecitation
CSF may be rendered sterile by administration of empirical antibiotics, within 2 h in meningococcal meningitis and within 4 h in pneumococcal meningitis.
“CSF may be rendered sterile by administration of empirical antibiotics, within 2 h in meningococcal meningitis and within 4 h in pneumococcal meningitis.43”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [43] Kanegaye, 2001, Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment, Pediatrics source
May combine two claims.
Premisecitation
CSF WCC may be normal (especially in early disease or immunodeficiency), and lymphocytes may predominate in partially antibiotic-treated ABM or L. monocytogenes meningitis.
“WCC, however, may be normal (especially in early disease or immunodeficiency), and lymphocytes may predominate in partially antibiotic-treated ABM or L. monocytogenes meningitis.42”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [42] Arevalo, 1989, Cerebrospinal fluid cell counts and chemistries in bacterial meningitis, South Med J source
May combine two claims.
Interpretationown data
ABM is an uncommon disease that continues to be associated with considerable morbidity and mortality among adults in the UK.
“ABM is an uncommon disease that continues to be associated with considerable morbidity and mortality among adults in the UK.”
Quote in the paperSubstantial claim
May combine two claims.
Interpretationreasoning
Lack of a confirmed microbiological diagnosis impedes pathogen-directed therapies, increases exposure to unnecessary broad-spectrum anti-infectives, potentially worsens outcomes, and hinders trials of new treatments.
“The lack of a confirmed microbiological diagnosis impedes pathogen-directed therapies, increases exposure to unnecessary broad spectrum anti-infectives, potentially worsens outcomes and hinders trials of new treatments.”
Quote in the paperSubstantial claim
Probably not a substantial claim: may not pass S3 (load-bearing).
Interpretationreasoning
Such vaccines have the potential to reduce the risk of serotype replacement and vaccine escape by providing pan-serotype pneumococcal protection.
“Such vaccines have the potential to reduce the risk of serotype replacement and vaccine escape by providing pan-serotype pneumococcal protection.”
Quote in the paperNot a substantial claim
Probably not a substantial claim: may not pass S2 (checkable), S4 (based).
Interpretationreasoning
In the context of changing epidemiology and the emergence of AMR, clinical diagnosis remains challenging.
“In the context of changing epidemiology and the emergence of AMR, clinical diagnosis remains challenging”
Quote in the paperNot a substantial claim

38 of 38

The paper relies on this without support.
Acute bacterial meningitis in adults is associated with a mortality that may exceed 30%.
“Acute bacterial meningitis (ABM) in adults is associated with a mortality that may exceed 30%.”
The paper relies on this without support.
There is continuing controversy and uncertainty over the best way to reduce the high mortality in ABM.
“In the light of continuing controversy and uncertainty over the best way to reduce the high mortality, we summarize the important future research directions.”
The paper relies on this without support.
Pathognomonic clinical examination findings do not exist for ABM.
“Pathognomonic clinical examination findings do not exist.”
The paper relies on this without support.
Often inappropriately small volumes of CSF are taken at LP, which limits diagnostic capacity.
“Often inappropriately small volumes of CSF are taken at LP, which limits diagnostic capacity.”
The paper relies on this without support.
A raised CSF white cell count (>5 cells/μl) with a predominance of neutrophils is typical of ABM.
“A raised CSF white cell count (WCC) (>5 cells/μl) with a predominance of neutrophils is typical of ABM.”
The paper relies on this without support.
The sensitivity of CSF culture depends upon whether antibiotics were administered pre- or post-CSF collection.
“The sensitivity of CSF culture depends upon whether antibiotics were administered pre-or post-CSF collection.”
The paper relies on this without support.
In contrast to CSF culture, PCR can detect bacterial DNA in CSF for several days after antibiotics have been administered.
“In contrast to CSF culture, polymerase chain reaction (PCR) can detect bacterial DNA in CSF for several days after antibiotics have been administered.”
The paper relies on this without support.
Resistance to penicillin resulting in treatment failure is rare for S. pneumoniae and extremely rare for N. meningitidis in the UK.
“Resistance to penicillin resulting in treatment failure is rare for S. pneumoniae and extremely rare for N. meningitidis in the UK.”
The paper relies on this without support.
There is little evidence to guide duration of antibiotics for ABM outside paediatric trials.
“There is little evidence to guide duration of antibiotics for ABM outside paediatric trials.”
The paper relies on this without support.
Since 2014 the UK and several other countries have seen a dramatic increase in MenW cases, accounting for 24% of IMD in England during 2014-15.
“However, since 2014 the UK and several other countries have seen a dramatic increase in MenW cases, accounting for 24% of IMD in England during 2014-15.”
The paper relies on this without support.
Matrix metalloproteinases (MMPs) are key immune mediators that promote blood-brain barrier disruption and brain injury.
“Matrix metalloproteinases (MMPs) are key immune mediators that promote BBB disruption and brain injury”
The paper relies on this without support.
Doxycycline is an effective MMP inhibitor.
“doxycycline is as an effective MMP inhibitor”
The paper relies on this without support.
Except for chloramphenicol, oral switches do not achieve sufficient antibiotic levels in the CSF.
“Except for chloramphenicol, oral switches do not achieve sufficient antibiotic levels in the CSF”
The paper relies on this without support.
Intravenous continuation therapy via outpatient antibiotic therapy (OPAT) services is increasingly being used for management of ABM.
“intravenous continuation therapy via outpatient antibiotic therapy (OPAT) services is increasingly being used for management of ABM”
The paper relies on this without support.
Close contacts of pneumococcal meningitis are not thought to have any increased risk.
“Close contacts of pneumococcal meningitis are not thought to have any increased risk”
The paper relies on this without support.
The antigenic diversity of S. pneumoniae and N. meningitidis challenges the success of current vaccines and particularly the generation of herd protection through the interruption of carriage and person-to-person spread.
“the antigenic diversity of S. pneumoniae and N. meningitidis challenges the success of current vaccines and particularly the generation of herd protection through the interruption of carriage and so person-to-person spread”
The paper relies on this without support.
Data on whether the recently introduced protein-based MenB vaccine prevents nasopharyngeal carriage has been conflicting to date.
“Data on whether the recently introduced proteinbased MenB vaccine prevents nasopharyngeal carriage has been conflicting to date.”

17 of 17

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

The Cochrane-review citation points to a rifampin study
Minor
The corticosteroid discussion cites reference 53 for the 2015 Cochrane review. Reference 53 is instead a retrospective study of rifampin use; the Cochrane review appears as reference 51.
The cited McGill report does not match reference 39
Minor
The text attributes the 42% figure to a 2018 McGill report and cites reference 39. That entry instead names Costerus and describes a study of CT, lumbar puncture and clinical deterioration.
The cited meningitis guideline points to a different paper
Minor
The text assigns citation 34 to the 2016 UK joint specialist societies' guideline, but reference 34 is a 2017 case series on otitis media. The guideline is listed as reference 32.

3 of 3

Clinical features and prognostic factors in adults with bacterial meningitis
van de Beek, D., de Gans, J., Spanjaard, L., Weisfelt, M., Reitsma, J. B., & Vermeulen, M. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040845 · Cited by 1,639 · see citing works
Acute Bacterial Meningitis in Adults -- A Review of 493 Episodes
Durand, M. L., Calderwood, S. B., Weber, D. J., Miller, S. I., Southwick, F. S., Caviness, V. S., & Swartz, M. N. (1993) · New England Journal of Medicine · doi:10.1056/nejm199301073280104 · Cited by 1,344 · see citing works
Dexamethasone in Adults with Bacterial Meningitis
de Gans, J., & van de Beek, D. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa021334 · Cited by 1,196 · see citing works
Epidemic meningitis, meningococcaemia, and Neisseria meningitidis
Stephens, D. S., Greenwood, B., & Brandtzaeg, P. (2007) · The Lancet · doi:10.1016/s0140-6736(07)61016-2 · Cited by 978 · see citing works
Corticosteroids for acute bacterial meningitis
Brouwer, M. C., McIntyre, P., Prasad, K., & van de Beek, D. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004405.pub5 · Cited by 809 · see citing works
Effect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction: an observational cohort study
Waight, P. A., Andrews, N. J., Ladhani, S. N., Sheppard, C. L., Slack, M. P. E., & Miller, E. (2015) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(15)70044-7 · Cited by 589 · see citing works
Planning, registration, and implementation of an immunisation campaign against meningococcal serogroup C disease in the UK: a success story
Miller, E. J., SALISBURY, D. M., & Ramsay, M. E. (2001) · Vaccine · doi:10.1016/s0264-410x(01)00299-7 · Cited by 483 · see citing works
Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites
Feikin, D. R., Kagucia, E. W., Loo, J. D., Link-Gelles, R., Puhan, M. A., Cherian, T., Levine, O. S., Whitney, C. G., O’Brien, K. L., Moore, M. R., et al. (2013) · PLoS Medicine · doi:10.1371/journal.pmed.1001517 · Cited by 470 · see citing works
Delays in the administration of antibiotics are associated with mortality from adult acute bacterial meningitis
Proulx, N., Frechette, D., Toye, B., Chan, J., & Kravcik, S. (2005) · QJM · doi:10.1093/qjmed/hci047 · Cited by 454 · see citing works
Lumbar Puncture in Pediatric Bacterial Meningitis: Defining the Time Interval for Recovery of Cerebrospinal Fluid Pathogens After Parenteral Antibiotic Pretreatment
Kanegaye, J. T., Soliemanzadeh, P., & Bradley, J. S. (2001) · Pediatrics · doi:10.1542/peds.108.5.1169 · Cited by 370 · see citing works
The Production of Cerebrospinal Fluid in Man and Its Modification by Acetazolamide
Rubin, R. C., Henderson, E. S., Ommaya, A. K., WALKER, M. D., & Rall, D. P. (1966) · Journal of neurosurgery · doi:10.3171/jns.1966.25.4.0430 · Cited by 324 · see citing works
Dilemmas in the diagnosis of acute community-acquired bacterial meningitis
Brouwer, M. C., Thwaites, G. E., Tunkel, A. R., & van de Beek, D. (2012) · The Lancet · doi:10.1016/s0140-6736(12)61185-4 · Cited by 302 · see citing works
Effectiveness and impact of a reduced infant schedule of 4CMenB vaccine against group B meningococcal disease in England: a national observational cohort study
Parikh, S. R., Andrews, N. J., Beebeejaun, K., Campbell, H., Ribeiro, S., Ward, C., White, J. M., Borrow, R., Ramsay, M. E., & Ladhani, S. N. (2016) · The Lancet · doi:10.1016/s0140-6736(16)31921-3 · Cited by 275 · see citing works
Acute bacterial meningitis in adults
McGill, F., Heyderman, R. S., Panagiotou, S., Tunkel, A. R., & Solomon, T. (2016) · The Lancet · doi:10.1016/s0140-6736(16)30654-7 · Cited by 274 · see citing works
Self-citation
The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults
McGill, F., Heyderman, R. S., Michael, B. D., Defres, S., Beeching, N. J., Borrow, R., Glennie, L., Gaillemin, O., Wyncoll, D., Kaczmarski, E., et al. (2016) · Journal of Infection · doi:10.1016/j.jinf.2016.01.007 · Cited by 254 · see citing works
Self-citation
Adjunctive dexamethasone in bacterial meningitis: a meta-analysis of individual patient data
van de Beek, D., Farrar, J., de Gans, J., Hoang, N. T., MOLYNEUX, E. M., Peltola, H., Peto, T., Roine, I., Scarborough, M., Schultsz, C., et al. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70023-5 · Cited by 241 · see citing works
Effect of antibiotic pretreatment on cerebrospinal fluid profiles of children with bacterial meningitis
Nigrovic, L. E., Malley, R., Macias, C. G., Kanegaye, J. T., Moro-Sutherland, D. M., Schremmer, R. D., Schwab, S. H., Agrawal, D., Mansour, K. M., Bennett, J. E., et al. (2008) · Pediatrics · doi:10.1542/peds.2007-3275 · Cited by 226 · see citing works
Host–pathogen interactions in bacterial meningitis.
Doran, K. S., Fulde, M., Gratz, N., Kim, B. J., Nau, R., Prasadarao, N., Schubert-Unkmeir, A., Tuomanen, E. I., & Valentin-Weigand, P. (2016) · Acta Neuropathologica · doi:10.1007/s00401-015-1531-z · Cited by 208 · see citing works
Incidence, aetiology, and sequelae of viral meningitis in UK adults: a multicentre prospective observational cohort study
McGill, F., Griffiths, M. J., Bonnett, L. J., Geretti, A. M., Michael, B. D., Beeching, N. J., McKee, D., Scarlett, P., Hart, I. J., Mutton, K. J., et al. (2018) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(18)30245-7 · Cited by 193 · see citing works
Meningococcal C conjugate vaccine: the experience in England and Wales
Campbell, H., Borrow, R., Salisbury, D., & Miller, E. (2009) · Vaccine · doi:10.1016/j.vaccine.2009.04.067 · Cited by 168 · see citing works
Outpatient parenteral antimicrobial therapy today
Paladino, J. A., & Poretz, D. (2010) · Clinical Infectious Diseases · doi:10.1086/653520 · Cited by 167 · see citing works
Mechanisms of injury in bacterial meningitis
Gerber, J., & Nau, R. (2010) · Current Opinion in Neurology · doi:10.1097/wco.0b013e32833950dd · Cited by 149 · see citing works
Trends in bacterial, mycobacterial, and fungal meningitis in England and Wales 2004–11: an observational study
Okike, I. O., Ribeiro, S., Ramsay, M. E., Heath, P. T., Sharland, M., & Ladhani, S. N. (2014) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(13)70332-3 · Cited by 138 · see citing works
Invasive meningococcal disease in England and Wales: implications for the introduction of new vaccines
Ladhani, S. N., Flood, J. S., Ramsay, M. E., Campbell, H., Gray, S. J., Kaczmarski, E. B., Mallard, R. H., Guiver, M., Newbold, L. S., & Borrow, R. (2012) · Vaccine · doi:10.1016/j.vaccine.2012.03.011 · Cited by 124 · see citing works
Increased Case‐Fatality Rate Associated with Outbreaks ofNeisseria meningitidisInfection, Compared with Sporadic Meningococcal Disease, in the United States, 1994–2002
Brooks, R., Woods, C. W., Benjamin, Jr., & Rosenstein, N. E. (2006) · Clinical Infectious Diseases · doi:10.1086/504804 · Cited by 124 · see citing works
PCR of peripheral blood for diagnosis of meningococcal disease
Newcombe, J., Cartwright, K. A. V., Palmer, W. H., & McFadden, J. (1996) · Journal of Clinical Microbiology · doi:10.1128/jcm.34.7.1637-1640.1996 · Cited by 122 · see citing works
Effect of delayed lumbar punctures on the diagnosis of acute bacterial meningitis in adults
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Retrospective analysis of the etiology, clinical characteristics and outcomes of community-acquired bacterial meningitis in the University Infectious Diseases Centre in Lithuania
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“Other risk factors for invasive disease include asplenia, CSF leakage from anatomic defects, and damage to the blood-brain barrier due to infections, namely, bacteremia and COVID-19 [5].”
BackgroundInfluential
Are cerebrospinal fluid biochemical parameters valid to predict positive results in microbiological molecular diagnostic platforms? A 4-year experience with the FilmArray® Panel Meningitis/Encephalitis for detection of community-acquired bacterial meningitis
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“” 47 (continued) ‐ Seizures: new onset, 11,47,55,57 – 61 or continuous or uncontrolled 54,62,63 ‐ Altered level of consciousness: GCS ≤ 9, 11 GCS ≤ 12, 54,62,63 moderate-to-severe impairment of consciousness, 47,57 – 61 or rapidly declining conscious level 54 ‐ Severe immunocompromised state…”
Influential
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“Notably, patients with bacterial meningitis may present without the classic signs of the disease, increasing the risk of misdiagnosis [2,3].”
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“However, molecular techniques are increasingly becoming useful [10] as they are more sensitive, rapid, and not affected by viability [11].”
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ACUTE BACTERIAL MENINGITIS MANAGEMENT IN ADULTS IS INADEQUATE: A MULTI–CENTRE AUDIT AND SURVEY
Needham, E., Brown, J. W. L., Senaratne, D. N. S., Karimi, A. M., Gibson, T. A., Brown, E. E., Kim, S., Thorpe, J. W., Boyle, A. A., & Coles, A. J. (2013) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2013-306573.8 · Cited by 1 · see citing works
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The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults
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Clinical management of community-acquired meningitis in adults in the UK and Ireland in 2017: a retrospective cohort study on behalf of the National Infection Trainees Collaborative for Audit and Research (NITCAR)
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Self-citation
Community-acquired bacterial meningitis in adults: emergency department management protocol
Smets, I., Verelst, S., Meyfroidt, G., Wijngaerden, E. V., Wilmer, A. P., Loon, J. V., Lagrou, K., & Dubois, B. (2020) · Acta Neurologica Belgica · doi:10.1007/s13760-020-01428-w · Cited by 5 · see citing works

Authors: Ellis, J., Luintel, A., Chandna, A., & Heyderman, R. S.
Affiliations: University College London Hospitals NHS Foundation Trust (GB)
Corresponding author: Ellis, Jayne
ORCID: Ellis, Jayne
Luintel, Akish
Chandna, Arjun
Heyderman, Robert S
Venue: British Medical Bulletin
Publisher: Oxford University Press (OUP)
Published: 2019-09
Volume: 131
Issue: 1
Pages: 57-70
ISSN: 0007-1420 (ISSN-L)
1471-8391
DOI: 10.1093/bmb/ldz023
OpenAlex: W2975263159
Cited by: 12
References: 62
Citations by year: 2026: 1 · 2025: 4 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 2
FWCI: 0.15
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor, 25 d)
Locations: British Medical Bulletin (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: National Institute for Health Research Health Protection Research Unit
National Institute for Health and Care Research (ACF-2017-20-001)
Public Health England
Topics: Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
Keywords: adults, mortality, clinical features, differential diagnosis, lumbar puncture, cerebrospinal fluid analysis, molecular diagnosis, guideline adherence, adjunctive corticosteroid therapy, brain herniation, pneumococcal conjugate vaccine, host inflammatory response, antibiotic regimens
MeSH terms: Adjuvants, Pharmaceutic, Adrenal Cortex Hormones, Adult, Antibodies, Bacteriological Techniques, Cerebrospinal Fluid, Drug Therapy, Combination, United Kingdom, Humans, Meningitis, Meningococcal, Neisseria meningitidis, Pneumococcal Infections, Specimen Handling, Spinal Puncture, Meningitis, Bacterial, Community-Acquired Infections, Antibiotic Prophylaxis, Neuroimaging

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Community-acquired acute bacterial meningitis in adults: a clinical update

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