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National Collaborating Centre for Women's and Children's Health (UK). Bacterial Meningitis and Meningococcal Septicaemia: Management of Bacterial Meningitis and Meningococcal Septicaemia in Children and Young People Younger than 16 Years in Primary and Secondary Care. London: RCOG Press; 2010. (NICE Clinical Guidelines, No. 102.)

2Development of the guideline

2.1. Bacterial meningitis and meningococcal septicaemia in children and young people

This guideline covers bacterial meningitis and meningococcal septicaemia, focusing on management of these conditions in children and young people aged younger than 16 years in primary and secondary care, and using evidence of direct relevance to these age groups where available.

Bacterial meningitis

Bacterial meningitis is an infection of the surface of the brain (meninges) by bacteria that have usually travelled there from mucosal surfaces via the bloodstream. In children and young people aged 3 months or older, the most frequent causes of bacterial meningitis include Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae type b (Hib; see table 2.1). These organisms occur normally in the upper respiratory tract and can cause invasive disease when acquired by a susceptible person. In neonates (children younger than 28 days), the most common causative organisms are Streptococcus agalactiae (Group B streptococcus), Escherichia coli, S. pneumoniae and Listeria monocytogenes (see table 2.2). These organisms are likely to be acquired around the time of birth from the maternal genital and gastrointestinal tract.1

Table 2.1. Incidence of and mortality from bacterial meningitis in children aged under 16 years in England and Wales by causative organism.

Table 2.1

Incidence of and mortality from bacterial meningitis in children aged under 16 years in England and Wales by causative organism.

Table 2.2. Incidence of bacterial meningitis in neonates (aged < 28 days) in England and Wales by causative organism, 1996–1997.

Table 2.2

Incidence of bacterial meningitis in neonates (aged < 28 days) in England and Wales by causative organism, 1996–1997.

The most recent UK national surveillance study of bacterial meningitis in neonates (aged under 28 days) was conducted in 1996–1997 and identified a case fatality rate of 10% in bacteriologically proven cases.3 Comparison with the previous national surveillance study (which was conducted in 1985–1987)4 revealed little change in the overall incidence of neonatal bacterial meningitis (0.22 cases per 1,000 live births in 1985–1987 versus 0.21 cases per 1,000 live births in 1996–1997). Although mortality has fallen significantly there has been no change in the rate of sequelae.5 A recent national study focusing specifically on Group B streptococcus in children in the first 90 days of life was conducted in 2000–2001 and reported a meningitis case fatality rate of 12.4%.6 Infection with L. monocytogenes is rare, accounting for approximately 5% of cases of neonatal meningitis; most cases involve early onset (age under 7 days), occur predominantly in premature infants and are related to maternal infection. Traditionally, pregnancy-associated L. monocytogenes has been considered capable of causing meningitis and sepsis in infants aged up to 3 months, but current epidemiological data indicate that nearly all pregnancy-associated cases present clinically in the first month of life: for example, of 72 cases of L. monocytogenes meningitis diagnosed between 1990 and 2007, only one occurred in an infant aged more than 4 weeks (source: Health Protection Agency [HPA], London).

The epidemiology of paediatric bacterial meningitis in the UK has changed dramatically in the past two decades following the introduction of vaccines developed to control the bacteria that cause meningitis. Hib was the main cause of bacterial meningitis in children aged under 5 years before the introduction of the Hib conjugate vaccine in 1992.7 It is now the third most common causative organism after N. meningitidis and S. pneumoniae (see table 2.1). Reduction in the incidence of disease caused by serogroup C meningococcus in the UK after the introduction of the meningococcal C (MenC) conjugate vaccine in 1999 has been equally marked.8 A reduction in the incidence of pneumococcal disease is already evident following the introduction of the pneumococcal conjugate vaccine in 2006* and is likely to decline further. The pneumococcal conjugate vaccine covers only seven serotypes of pneumococcus, although 91 have been described.9 As no vaccine is currently licensed against serogroup B meningococcus, this pathogen is now the most common cause of bacterial meningitis (and septicaemia) in children and young people aged 3 months or older (see HPA guidance).

The incidence of pneumococcal meningitis in children younger than 3 months may decline as a result of vaccination through population (or ‘herd’) immunity. However, serotypes not included in the current vaccine (for example ST1), appear to be more likely to cause disease in this age group than in older age groups. For example, the percentage of invasive pneumococcal disease serotypes found in the seven-valent vaccine before widespread vaccination was 47% for those aged under 1 month compared with 88% for children aged 1 to 4 years.10 Thus, population immunity with the current pneumococcal conjugate vaccine may have minimal impact on pneumococcal meningitis in children younger than 3 months.

This guideline does not consider meningitis associated with tuberculosis (TB), because tuberculous meningitis (or meningeal TB) is covered in ‘Tuberculosis: clinical diagnosis and management of tuberculosis, and measures for its prevention and control’, National Institute for Health and Clinical Excellence (NICE) clinical guideline 33.11 However, some features of the presentation of tuberculous meningitis are indistinguishable from bacterial meningitis.

Meningococcal disease

Most N. meningitidis colonisations are asymptomatic, but occasionally the organism invades the bloodstream (usually within a few days of a susceptible person acquiring the organism) to cause meningococcal disease. Meningococcal disease most commonly presents as bacterial meningitis (15% of cases) or septicaemia (25% of cases), or as a combination of the two syndromes (60% of cases).12 Rarely the disease presents as pneumonia, arthritis, osteomyelitis, pericarditis, endophthalmitis or conjunctivitis.13 Meningococcal disease is the leading infectious cause of death in early childhood,14 making its control a priority for clinical management (as well as public health surveillance and control; see below). The disease can be fatal within hours of the first symptoms appearing, and many experts believe that lives could be saved by earlier recognition and prompt and appropriate emergency management. This view is supported by research in adults on the ‘golden hours’ that suggests that the initial management of patients with meningococcal disease may be critical in determining outcome**.

Disease-causing meningococci are encapsulated with polysaccharides, the chemical nature of which determines the serogroup of the organism. Serogroups A, B, C, W135 and Y are the main causes of invasive meningococcal disease.15 Most meningococcal disease in Europe is caused by serogroups B and C, but the serogroup distribution varies over time: following the introduction of the MenC conjugate vaccine (which protects against serogroup C meningococcus), almost all cases of meningococcal disease in England and Wales are now caused by serogroup B.15

The highest incidence of meningococcal disease occurs among children aged under 2 years; another period of increased risk occurs in adolescence and early adulthood.15 The disease is more frequent in winter months15 and is associated with smoking, crowding and recent viral respiratory illness.16–19 The case fatality rate is about 10%,20 with the highest mortality rates occurring in people with fulminant meningococcal septicaemia (meningococcal septicaemia that strikes suddenly and with great severity).21

Notification and public health management

Under the Health Protection (Notification) Regulations 2010,†† registered medical practitioners in England have a legal requirement to notify the proper officer of the local authority in which the patient resides when they have reasonable grounds for suspecting that the patient has a notifiable disease as listed in Schedule 1 of the Regulations. From October 2010, the Regulations will place a duty on diagnostic laboratories to notify the HPA when they identify evidence of infection caused by specified causative agents. Prior notification by a diagnostic laboratory does not remove the registered medical practitioner’s responsibility to notify a notifiable disease.

The Regulations identify those diseases which should be notified urgently. Urgent notifications are to be made orally, usually by telephone, as soon as is reasonably practicable and always within 24 hours. Oral notification should be followed by a written notification to be received by the proper officer within 3 days of the clinical suspicion being formed. This is the case for clinical and laboratory diagnoses. Acute meningitis (including bacterial meningitis) and meningococcal septicaemia are notifiable diseases requiring urgent notification. From the laboratory perspective, N. meningitidis should be reported urgently. The Department of Health has issued guidance22 explaining the notification requirements on registered medical practitioners and diagnostic laboratories that test human samples, and health protection powers available to local authorities and justices of the peace.***

The purposes of notification are to prompt local investigation and public health action to control these diseases, including prevention of nosocomial (healthcare associated) transmission and transmission in the community. The resulting data are also used for analysis of local and national trends. The HPA has issued guidance on public health management of meningococcal disease in the UK15 which covers laboratory investigation of suspected cases, local and national public health surveillance, and public health action after a case to prevent secondary infection, including chemoprophylaxis (using antibiotics and/or vaccines) in close contacts, the wider community and healthcare settings.††† Specific recommendations contained in the HPA guidance include:

  • isolation of the index case during the first 24 hours of treatment with antibiotics (after this the index case ceases to be infectious)23
  • use of surgical masks by healthcare professionals during initial management to reduce the possibility of exposure to large particle droplets (especially during airway management procedures), so avoiding the need for chemoprophylaxis
  • use of chemoprophylaxis only for those healthcare professionals whose mouth or nose is directly exposed to large particle droplets or secretions from the respiratory tract of a probable or confirmed case of meningococcal disease during acute illness until 24 hours of systemic antibiotics has been completed: general medical or nursing care of cases is not an indication for prophylaxis.

2.2. Aim and scope of the guideline

This clinical guideline concerns the management of bacterial meningitis and meningococcal septicaemia in children and young people younger than 16 years in primary and secondary care. It has been developed with the aim of providing guidance in the following areas:

  • diagnosis of bacterial meningitis and meningococcal septicaemia (covering symptoms and signs, identification of levels of risk based on probabilities of combinations of signs and symptoms, and differentiating between meningococcal septicaemia and other causes of non-blanching rash)
  • management of suspected bacterial meningitis and meningococcal septicaemia in primary care and in the pre-hospital setting
  • management of bacterial meningitis and meningococcal septicaemia in secondary care, covering:

    choice of antibiotics

    fluid resuscitation

    timing and role of intubation and the decision to initiate it

    corticosteroids for the treatment of meningitis

    use of scoring systems such as the Glasgow meningococcal septicaemia prognostic score (GMSPS) in diagnosis and management

    the role of recombinant bacterial permeability increasing protein (Bpi) and activated protein C

  • retrieval and transfer to secondary and tertiary care
  • choice and timing of investigations:

    blood tests, aspirates and swabs

    lumbar puncture

    radiology and immunological testing

  • information that should be given to parents and carers (at the time of initial presentation and after diagnosis, regarding short- and long-term effects, and including significant psychological and physical morbidities).

The following groups are specifically excluded from the guideline:

  • children and young people with known immunodeficiency
  • children and young people with brain tumours, existing hydrocephalus or intracranial shunts
  • neonates already receiving care in neonatal units.

Further information about the areas covered in the guideline is available in the ‘scope’ of the guideline (reproduced in appendix A).

2.3. For whom is the guideline intended?

This guideline is of relevance to those who work in or use the National Health Service (NHS) in England, Wales and Northern Ireland, in particular:

  • healthcare professionals involved in the care of children and young people with bacterial meningitis or meningococcal septicaemia, including paediatricians, general practitioners (GPs) and nurses
  • those responsible for commissioning and planning healthcare services, including primary care trust commissioners, Health Commission Wales commissioners, and public health and trust managers
  • parents and carers of children and young people with bacterial meningitis or meningococcal septicaemia.

A version of this guideline for patients and their parents and carers is available from the NICE website (www.nice.org.uk/CG102) or from NICE publications on 0845 003 7783 (quote reference number N2202).

2.4. Other relevant documents

This guideline is intended to complement other existing and proposed works of relevance, including the following guidance published by NICE:

This guideline also draws on clinical questions and searches developed for the Scottish Intercollegiate Guidelines Network (SIGN) clinical guideline on management of invasive meningococcal disease in children and young people.27 The Department of Health guidance on health protection legislation in England****22 and the HPA guidance on public health management of meningococcal disease in the UK15 should also be considered in conjunction with this guideline (see section 3).

2.5. Who has developed the guideline?

The guideline was developed by a multi-professional and lay Guideline Development Group (GDG) convened by the National Collaborating Centre for Women’s and Children’s Health (NCC-WCH). Membership included:

  • eight paediatricians (including paediatricians specialising in emergency medicine and infectious diseases)
  • a GP
  • two nurses specialising in paediatric critical care
  • a public health physician
  • two patient/carer members.

NCC-WCH staff provided methodological support for the guideline development process, undertook systematic searches, retrieved and appraised the evidence, developed health economic models and wrote successive drafts of the guideline.

Two external advisers were appointed by the GDG to advise on topics relevant to the guideline.

All GDG members’ and external advisers’ potential and actual conflicts of interest were recorded on declaration forms provided by NICE (summarised in appendix B). None of the interests declared by GDG members constituted a material conflict of interest that would influence recommendations developed by the GDG.

Organisations with interests in the management of bacterial meningitis and meningococcal septicaemia in children and young people aged under 16 years were encouraged to register as stakeholders for the guideline. Registered stakeholders were consulted throughout the guideline development process. The types of organisations eligible to register as stakeholders included:

  • national patient and carer organisations that directly or indirectly represent interests of children and young people aged under 16 years with bacterial meningitis or meningococcal septicaemia and their families
  • national organisations that represent healthcare professionals who provide services for children and young people aged under 16 years with bacterial meningitis or meningococcal septicaemia
  • companies that manufacture preparations and/or products used in the management of bacterial meningitis or meningococcal septicaemia in children and young people aged under 16 years
  • providers and commissioners of health services in England, Wales and Northern Ireland
  • statutory organisations such as the Department of Health and the Welsh Assembly Government
  • research organisations that have undertaken nationally recognised research in relation to the topics covered in the guideline.

A list of registered stakeholder organisations for this guideline is presented in appendix C.

2.6. Guideline development methodology

This guideline was commissioned by NICE and developed in accordance with the process outlined in successive editions of ‘The guidelines manual’.***** Table 2.3 summarises the key stages of the process and which version of the guidelines manual was followed at each stage. In accordance with NICE’s Equality Scheme††††, ethnic and cultural considerations and factors relating to disabilities were considered by the GDG at every stage of the process and addressed specifically in individual recommendations where relevant.

Table 2.3. Stages in the NICE guideline development process and versions of ‘The guidelines manual’ followed at each stage.

Table 2.3

Stages in the NICE guideline development process and versions of ‘The guidelines manual’ followed at each stage.

Developing clinical questions and identifying evidence

The GDG formulated clinical questions based on the scope (see appendix D). These formed the starting point for subsequent evidence reviews. Relevant published evidence to answer the clinical questions was identified by applying systematic search strategies (see appendix E) to the following databases:

  • Medline (1950 onwards)
  • Embase (1980 onwards)
  • Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 onwards using the Ovid platform and 1987 onwards using the Ebsco platform)
  • three Cochrane databases (Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effects).

PsycInfo (1967 onwards) was also searched for evidence related to long-term sequelae of bacterial meningitis and meningococcal disease and the NHS Economic Evaluation Database (NHS EED) was also searched to identify economic studies. Except where specifically stated, the searches were not limited by date or language of publication (although publications in languages other than English were not reviewed). Generic and specially developed search filters were used to identify particular study designs, such as randomised controlled trials (RCTs). There was no systematic attempt to search grey literature (conferences, abstracts, theses and unpublished trials) and hand searching of journals not indexed on the databases was not undertaken.

Towards the end of the guideline development process, the searches were updated and reexecuted, to include evidence published and indexed in the databases by 1 June 2009.

Reviewing and grading evidence

Evidence relating to clinical effectiveness was reviewed and graded using the hierarchical system presented in table 2.4. This system reflects the susceptibility to bias inherent in particular study designs.

Table 2.4. Levels of evidence for intervention studies.

Table 2.4

Levels of evidence for intervention studies.

The type of clinical question dictates the highest level of evidence that may be sought. In assessing the quality of evidence, each study was assigned a quality rating coded as ‘++’, ‘+’ or ‘−’. For issues of therapy or treatment, the highest possible evidence level (EL) is a well-conducted systematic review or meta-analysis of RCTs (EL = 1++) or an individual RCT (EL = 1+). Studies of poor quality were rated as ‘−’. Studies rated as ‘−’ should not be used as a basis for making a recommendation, but they may be used to inform recommendations. For issues of prognosis, the highest possible level of evidence is a cohort study (EL = 2).

For each clinical question, the highest available level of evidence was sought. Where appropriate (for example, if a systematic review, meta-analysis or RCT was identified to answer a question), studies of a weaker design were not considered. Where systematic reviews, meta-analyses and RCTs were not identified, other appropriate experimental or observational studies were sought. For diagnostic tests, test evaluation studies examining the performance of the test were used if the effectiveness (accuracy) of the test was required, but where an evaluation of the effectiveness of the test in the clinical management of patients and the outcome of disease was required, evidence from RCTs or cohort studies was optimal. For studies evaluating the accuracy of a diagnostic test, sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs) were calculated or quoted where possible (see table 2.5). Likelihood ratios (LRs) were also quoted where reported.

Table 2.5. ‘2 × 2’ table for calculation of diagnostic accuracy parameters.

Table 2.5

‘2 × 2’ table for calculation of diagnostic accuracy parameters.

The hierarchical system described above covers studies of treatment effectiveness. However, it is less appropriate for studies reporting accuracy of diagnostic tests. In the absence of a validated ranking system for this type of test, NICE has developed a hierarchy of evidence that takes into account various factors likely to affect the validity of such studies (see table 2.6).

Table 2.6. Levels of evidence for studies of the accuracy of diagnostic tests.

Table 2.6

Levels of evidence for studies of the accuracy of diagnostic tests.

Some studies were excluded from the reviews after obtaining copies of the corresponding publications because they did not meet inclusion criteria specified by the GDG (see appendix F). Clinical evidence from included studies was extracted into evidence tables for each question (see appendix G), and a brief summary of each study was included in the guideline text. Where possible, dichotomous outcomes are presented as relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs), and continuous outcomes are presented as mean differences with 95% CIs or standard deviations (SDs).

The body of evidence identified for each clinical question was synthesised qualitatively in clinical evidence statements. Quantitative synthesis (meta-analysis) was also undertaken for specific areas of the guideline, with results being presented in the text as pooled RRs, pooled ORs or weighted mean differences (WMDs). By default, meta-analyses were conducted by fitting fixed effects models, but where statistically significant heterogeneity was identified, random effects models were used. Forest plots are presented for the effectiveness of empiric antibiotics for the treatment of suspected bacterial meningitis and effectiveness of corticosteroids for the treatment of bacterial meningitis (see appendix H).

Incorporating health economics

The aims of the health economic input to the guideline were to inform the GDG of potential economic issues relating to the management of bacterial meningitis and meningococcal septicaemia in children and young people aged under 16 years, and to ensure that recommendations represented a cost-effective use of healthcare resources. Health economic evaluations aim to integrate data on benefits or harms (ideally in terms of quality adjusted life years [QALYs]) and costs of different care options.

The GDG prioritised a number of clinical questions where it was thought that economic considerations would be particularly important in formulating recommendations. For this guideline the areas prioritised for economic analysis were:

GDG interpretation of the evidence and creating recommendations

For each clinical question, recommendations for clinical care were derived using, and linked explicitly to, the evidence that supported them. In the first instance, informal consensus methods were used by the GDG to agree clinical and, where appropriate, cost-effectiveness evidence statements. Statements summarising the GDG’s interpretation of the evidence and any extrapolation from the evidence used to form recommendations were also prepared to ensure transparency in the decision-making process.

In areas where no substantial clinical research evidence was identified, the GDG considered other evidence-based guidelines and consensus statements or used their collective experience to identify good practice. The health economics justification in areas of the guideline where the use of NHS resources (interventions) was considered was based on GDG consensus in relation to the likely cost-effectiveness implications of the recommendations. The GDG also identified areas where evidence to answer its clinical questions was lacking and used this information to formulate recommendations for future research.

Towards the end of the guideline development process, formal consensus methods were used to consider all the clinical care recommendations and research recommendations that had been drafted previously. The GDG identified ten ‘key priorities for implementation’ (key recommendations) and five high priority research recommendations. The key priorities for implementation were those recommendations likely to have the biggest impact on patients’ care and outcomes in the NHS as a whole; they were selected using a variant of the nominal group technique (see the NICE guidelines manual). The priority research recommendations were selected in a similar way.

Stakeholder involvement in the guideline development process

Registered stakeholder organisations were invited to comment on the draft scope and the draft guideline. Stakeholder organisations were also invited to undertake a pre-publication check of the final guideline to identify factual inaccuracies. The GDG carefully considered and responded to all comments received from stakeholder organisations. The comments and responses, which were reviewed independently for NICE by a guideline review panel, are published on the NICE website.

2.7. Specific considerations for this guideline

For this guideline, the effectiveness of interventions was assessed against the following broad outcome categories:

  • mortality
  • loss of limbs
  • relapse of infection
  • duration of hospital stay
  • need for rehabilitation
  • adverse effects of antibiotic treatment
  • immediate, short-term and long-term neurological complications including:

    hearing loss

    visual impairment

    mobility and ambulation problems

    psychosocial/behavioural problems.

Some of the clinical questions developed for the SIGN guideline****** on management of invasive meningococcal disease in children and young people27 were sufficiently similar to clinical questions developed for this guideline that SIGN search strategies could be updated and used as search strategies for this guideline. For other questions, the GDG developed original search strategies. Some searches were restricted by year of publication, for example to target studies conducted after the introduction of the Hib conjugate vaccine, or by country of study, for example to target studies conducted in high-income (developed) countries, so that the pathogens and clinical settings reported in the studies were relevant to current epidemiology and NHS clinical practice in England in Wales (see individual chapters for further details). Studies involving adults as well as children and young people were included where data were presented separately for children and/or young people.

Where the evidence supported it, the GDG made separate recommendations for the management of different conditions (bacterial meningitis, meningococcal septicaemia and, in some cases, meningococcal disease). Unless otherwise specified, the recommendations refer to all children and young people aged under 16 years. The GDG also used the term neonate in some recommendations.

2.8. Schedule for updating the guideline

Clinical guidelines commissioned by NICE are published with a review date 3 years from the date of publication. Reviewing may begin before 3 years have elapsed if significant evidence that affects guideline recommendations is identified sooner.

In this revised reprint, the hydrocortisone dosage in the recommendation relating to steroid replacement therapy using low-dose corticosteroids in children and young people with shock that is unresponsive to vasoactive agents has been corrected (see Sections 1.2 and 6.8). The care pathway has also been revised to reflect the action required when meningococcal meningitis is confirmed in children older than 3 months (see Section 1.5).

Copyright © 2010, Royal College of Obstetricians and Gynaecologists.

No part of this publication may be reproduced, stored or transmitted in any form or by any means, without the prior written permission of the publisher or, in the case of reprographic reproduction, in accordance with the terms of licences issued by the Copyright Licensing Agency in the UK [www.cla.co.uk]. Enquiries concerning reproduction outside the terms stated here should be sent to the publisher at the UK address printed on this page.

The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant laws and regulations and therefore for general use.

Cover of Bacterial Meningitis and Meningococcal Septicaemia
Bacterial Meningitis and Meningococcal Septicaemia: Management of Bacterial Meningitis and Meningococcal Septicaemia in Children and Young People Younger than 16 Years in Primary and Secondary Care.
NICE Clinical Guidelines, No. 102.
National Collaborating Centre for Women's and Children's Health (UK).
London: RCOG Press; 2010.

NICE (National Institute for Health and Care Excellence)

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