Clinical Topic A-Z Clinical Speciality

Meningitis (bacterial)/meningococcal septicaemia

Meningitis (bacterial)/meningococcal septicaemia
D008581Meningitis
D008589Meningococcal Infections
Child healthInfections and infestations
2011-01-01Last revised in January 2011

Meningitis (bacterial)/meningococcal septicaemia - Summary

Meningitis is a condition caused by inflammation of the meninges (the outer membranes covering the brain and spinal cord).

Causes of meningitis can be infective (bacterial, viral, and fungal) or non-infective (certain cancers, autoimmune disorders, and drugs).

Bacterial meningitis is a life-threatening condition that can affect all ages, but is most common in young people and children.

Streptococcus pneumoniae and Neisseria meningitides are the most common causative organisms of acute bacterial meningitis in children and adults, being responsible for nearly 80% of all cases.

Meningitis resulting from infection with Streptococcus pneumoniae is known as pneumococcal disease; meningitis resulting from infection with N. meningitides (also called meningococcus) is known as meningococcal disease.

Meningococcal septicaemia is a result of N. meningitides entering the bloodstream and causing blood poisoning.

Transmission occurs through close contact, by droplets or direct contact with respiratory secretions.

The annual incidence of acute bacterial meningitis in developed countries is 2 to 5 per 100,000 population. It is one of the top 10 causes of infection-related death worldwide, with 30–50% of survivors experiencing permanent neurological sequelae.

Clinical features of acute bacterial meningitis include:

Non-specific symptoms: fever, nausea and vomiting, lethargy, irritable or unsettled mood, refusal of food and drink, headache, muscle ache or joint pain, and respiratory symptoms and signs.

More specific symptoms: stiff neck, altered mental state (confusion, delirium and drowsiness, impaired consciousness), non-blanching rash, back rigidity, bulging fontanelle (in children younger than 2 years of age), photophobia, Kernig's sign, Brudzinski's sign, unconsciousness, toxic or moribund state, paresis, focal neurological deficit (including cranial nerve involvement and abnormal pupils), and seizures.

Bacterial meningitis and meningococcal septicaemia are medical emergencies and require immediate admission to hospital.

If there is a non-blanching rash, parenteral benzylpenicillin should be given pre-admission (unless the person is allergic to penicillin).  

The management of close contacts (involving prophylactic measures) should be undertaken in conjunction with the local or regional health protection unit.

Prophylaxis against meningococcal disease should be considered for people who have had prolonged close contact with the case in a household-type setting during the 7 days before onset of illness, and people who have had transient close contact with a case only if they have been directly exposed to large particle droplets or secretions from the respiratory tract of a case around the time of admission to hospital.

Close contacts of individual cases of pneumococcal meningitis are not at increased risk of pneumococcal infection and do not require antibiotic prophylaxis or immunization.

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This CKS topic covers the primary care management of suspected acute bacterial meningitis and meningococcal septicaemia in children and adults. It also covers how to manage close contacts of a person with confirmed bacterial meningitis or meningococcal septicaemia.

This CKS topic is based mainly on the clinical guideline Bacterial meningitis and meningococcal septicaemia published by the National Institute for Health and Clinical Excellence (NICE) [NICE, 2010a], the clinical guideline Management of invasive meningococcal disease in children and young people published by the Scottish Intercollegiate Guidelines Network (SIGN) [SIGN, 2008], and the Guidance for public health management of meningococcal disease in the UK published by the Health Protection Agency (updated in January 2011) [HPA, 2011].

This CKS topic does not cover the diagnosis and management of meningitis and meningococcal septicaemia in secondary care.

There are separate CKS topics on Feverish children - risk assessment, Feverish children - management, Immunizations - childhood, and Immunizations - pneumococcal.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary healthcare.

How up-to-date is this topic?

How up-to-date is this topic?

Changes

Last revised in January 2011

July 2013 — minor update. Links to the DVLA website have been updated.

May 2011 — minor update. Text on prophylactic treatment for close contacts updated to reflect amendments to Immunization against infectious disease — 'The Green Book' from the Department of Health [DH, 2011]. Issued in June 2011.

October 2010 to February 2011 — this is a new CKS topic.

Update

New evidence

NICE Evidence published an evidence update on bacterial meningitis and meningococcal septicaemia in January 2012. [Free Full-text (pdf)]

Evidence-based guidelines

No new evidence-based guidelines since 1 October 2010.

HTAs (Health Technology Assessments)

No new HTAs since 1 October 2010.

Economic appraisals

No new economic appraisals relevant to England since 1 October 2010.

Systematic reviews and meta-analyses

Systematic reviews published since the last revision of this topic:

Borchorst, S., and Moller, K. (2012) The role of dexamethasone in the treatment of bacterial meningitis – a systematic review. Acta Anaesthesiologica Scandinavica 56(10), 1210-1221. [Abstract]

Kulik, D.M., Uleryk, E.M. and Maguire, J.L. (2013) Does this child have bacterial meningitis? A systematic review of clinical prediction rules for children with suspected bacterial meningitis. Journal of Emergency Medicine 45(4), 508-519. [Abstract]

Primary evidence

No new randomized controlled trials published in the major journals since 1 October 2010.

New policies

No new national policies or guidelines since 1 October 2010.

New safety alerts

No new safety alerts since 1 October 2010.

Changes in product availability

No changes in product availability since 1 October 2010.

Goals and outcome measures

Goals

To support primary healthcare professionals:

To make a diagnosis of suspected bacterial meningitis and meningococcal septicaemia

To provide appropriate management of all suspected cases in primary care

To manage the close contacts of a person with confirmed bacterial meningitis or meningococcal septicaemia

Background information

Definition

What is it?

Meningitis is a condition caused by the inflammation of the meninges (the outer membranes covering the brain and spinal cord).

This is different from encephalitis, which is due to inflammation of the brain tissue itself.

Causes of meningitis can be infective (bacterial, viral, and fungal) and non-infective (certain cancers, autoimmune disorders, and drugs).

For further information, see Differential diagnosis in Diagnosis under Management.

Bacterial meningitis is a life-threatening condition that affects all ages, but is most common in young people and children (see Prevalence).

Streptococcus pneumoniae and Neisseria meningitidis are the most common causative organisms of acute bacterial meningitis in children and adults [Chaudhuri et al, 2008]. For further information, see Causes.

Meningococcal septicaemia is a result of N. meningitidis entering the bloodstream and causing blood poisoning. For further information on meningococcal infection, see Meningococcal disease under Causes.

[Hopkins and Jolles, 2005; Chaudhuri et al, 2008; Branco and Tasker, 2010; DH, 2006; National Collaborating Centre for Women's and Children's Health, 2010]

Causes

What causes bacterial meningitis?

Bacterial meningitis can arise as a result of [Begg et al, 1999]:

Direct spread of the infection into the cerebrospinal fluid from adjacent structures (such as sinuses, mastoids or bone [such as spinal osteomyelitis]) or

A complication of bacteraemia from a distant source.

Only a relatively small number of bacteria are responsible for most cases of acute bacterial meningitis. There is still uncertainty regarding how these pathogens cross the blood-brain barrier and cause meningitis.

In the developed world, the bacterial pathogens responsible for acute bacterial meningitis vary with age [Tunkel et al, 2004; Kim, 2010]:

Younger than 1 month of age: Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes, and Klebsiella species. These organisms are usually acquired around the time of birth from the maternal genital and gastrointestinal tract [Saez-Llorens and McCracken, 2003].

From 1–3 months of age: Streptococcus pneumoniae, Neisseria meningitidis, S. agalactiae, Haemophilus influenzae, and E. coli.

From 3 months–50 years of age: N. meningitidis and S. pneumoniae.

Older than 50 years of age: S. pneumoniae, N. meningitidis, L. monocytogenes, and aerobic Gram-negative bacilli.

S. pneumoniae and N. meningitidis are the most common causative organisms of acute bacterial meningitis in children and adults, responsible for nearly 80% of all cases [Chaudhuri et al, 2008].

Since the introduction of the pneumococcal conjugate vaccine in 2006, a reduction in the incidence of pneumococcal disease is already evident and is likely to decline further.

N. meningitidis (serogroup B) is the most common cause of bacterial meningitis and septicaemia in children and young people.

For further information, see What causes meningococcal disease? and What causes pneumococcal meningitis?

[DH, 2010; Meningitis Research Foundation, 2010; National Collaborating Centre for Women's and Children's Health, 2010]

Meningococcal disease

What is the cause of meningococcal disease?

Meningococcal disease is the term used to describe the three different presentations of invasive meningococcal infection caused by the Gram-negative aerobic bacterium, Neisseria meningitidis (also called meningococcus):

Bacterial meningitis (15% of cases).

Meningococcal septicaemia (25% of cases).

The combination of both bacterial meningitis and meningococcal septicaemia (60%).

It is transmitted through close contact in droplets or secretions from the upper respiratory tract. Transmission usually requires either frequent or prolonged close contact.

Neisseria meningitidis is usually commensal, with 5–11% of adults and up to 25% of adolescents being asymptomatic carriers. However, the carriage rate is low in infants and young children.

Using data from 89 cross-sectional and longitudinal studies, one meta-analysis (search date: up to March 2010) reported carriage prevalence increased through childhood from 4.5% in infants to a peak of 23.7% in 19-year olds, before declining in adulthood to 7.8% in 50-year olds [Christensen et al, 2010].

It is uncertain why the disease develops in some people but not in others. For information on risk factors for meningococcal disease, see Risk factors.

Incubation period is from 2 to 7 days.

The onset of disease can vary from fulminant with acute and overwhelming symptoms to insidious with mild prodromal symptoms.

There are at least 13 meningococcal serogroups; A, B, C, W135, and Y cause most cases of meningococcal disease.

Serogroups B and C used to be responsible for the majority of invasive meningococcal disease in UK. However, invasive disease caused by serogroup C has been rare since the introduction of the meningococcal C vaccine (for further information, see the CKS topic on Immunizations - childhood).

Currently, there is no vaccine against serogroup B, which is now responsible for the majority of meningococcal disease in all age groups.

For the period 2008/2009, the Health Protection Agency reported only 13 cases of serogroup C infection (corresponding to 1.1% of reported meningococcal infections). This contrasts with a figure of 1052 cases (90.2%) for serogroup B infection [HPA, 2010b].

Meningococcal disease occurs in all countries — with the highest incidence in sub-Saharan Africa ('meningitis belt') where outbreaks (involving serogroups A, W135, and X) can occur within a very short period of time (at the end of dry, dusty season).

Large epidemics of meningococcal disease have been linked to the annual Hajj pilgrimage to Mecca in Saudi Arabia. This has resulted in importations of serogroup A and W135 infections into the UK and to other countries. Consequently, evidence of receipt of quadrivalent vaccine (serogroups A, C, Y, W135) is now an entry requirement to Saudi Arabia (for further information, see the CKS topic on Immunizations - travel).

Although most cases of bacterial meningitis arise sporadically, only meningococcal disease can occur in epidemic form [Saez-Llorens and McCracken, 2003].

[SIGN, 2008; DH, 2010; Meningitis Research Foundation, 2010; National Collaborating Centre for Women's and Children's Health, 2010]

Pneumococcal meningitis

What is the cause of pneumococcal meningitis?

Pneumoccal disease is the term used to describe infections caused by the encapsulated Gram-positive bacterium Streptococcus pneumoniae (also called pneumococcus).

The capsule is the most important characteristic of S. pneumoniae; pneumococci that lack a capsule are not normally virulent.

Although over 90 different capsular types have been characterized, only 8–10 capsular types are responsible for around 66% cases of serious infections in adults and around 80% of invasive infections in children.

The organism is transmitted through close contact, by droplets or direct contact with respiratory secretions.

It usually gains entry into the body by colonizing the nasopharyngeal mucosal epithelium.

Depending on the site of colonization, S. pneumoniae may cause sinusitis (via nasal sinus), otitis media (in the middle ear cavity), pneumonia, and systemic (invasive) infections, which include bacteraemic pneumonia, bacteraemia, and meningitis.

Invasive pneumococcal disease (IPD) is a major cause of morbidity and mortality, particularly affecting very young people, elderly people, and people who are asplenic or immunocompromised (see Prevalence and Risk factors).

Consequently, pneumococcal vaccination is now offered to all adults older than 65 years of age and to all children (as part of the childhood immunization programme), as well as to high-risk groups. For further information, see the CKS topics on Immunizations - childhood and Immunizations - pneumococcal.

S. pneumoniae rarely causes clusters of serious disease including septicaemia, pneumonia and meningitis in closed settings.

[HPA, 2008; DH, 2006]

Prevalence

How common is it?

The annual incidence of acute bacterial meningitis in developed countries is estimated to be 2 to 5 per 100,000 population. This may be ten times higher in undeveloped countries [Chaudhuri et al, 2008].

It is one of the top 10 causes of infection-related death worldwide with 30–50% of survivors experiencing permanent neurological sequelae (see Prognosis and Complications) [Chaudhuri et al, 2008].

The main causes of acute bacterial meningitis are Neisseria meningitidis and Streptococcus pneumoniae.

N. meningitidis (serogroup B) is the most common cause of bacterial meningitis and septicaemia in children and young people in the UK (see Causes).

Bacterial meningitis and meningococcal septicaemia are more frequent in children and young people (see below).

In adults, one study reported that [Gjini et al, 2006]:

The mean annual incidence of community-acquired bacterial meningitis in England and Wales to be around 0.6 cases per 100,000 (for the period 1991–2002, based on laboratory reports).

S. pneumoniae (predominantly in older adults) and N. meningitidis (predominantly in young adults) together accounted for 78% of cases.

Meningococcal disease

The incidence in UK has declined slightly in recent years — with an average annual incidence of 2.05 per 100,000 population between 2006/2007 to 2009/2010 [HPA, 2011].

It has been estimated that the average GP will see only one or two cases of meningococcal disease in his or her career in primary care [Hart and Thomson, 2006; National Collaborating Centre for Women's and Children's Health, 2010].

Around 50% of meningococcal disease in the UK occurs in children younger than 4 years of age.

Pneumoccal meningitis

In England and Wales, 5.5% of reported case of invasive pneumococcal disease (IPD) are meningitis (laboratory confirmed, period 1996–2005) [HPA, 2009].

Approximately 5000–6000 cases of IPD are reported annually to the Health Protection Agency (HPA) [HPA, 2010a]. The annual incidence of IPD is approximately 12 per 100,000 population [HPA, 2008].

Young children (younger than 2 years of age) and the elderly are most at risk of IPD (see Risk factors).

Latest published figures from the HPA reported 252 laboratory-confirmed cases of pneumoccal meningitis for 2004/2005. Of these, 29.3% cases were in children 1 year of age and younger, and 40.0% were in adults 45 years of age and older [HPA, 2009].

Other causes of bacterial meningitis

Other bacteria are responsible for a minority of cases of bacterial meningitis.

The British Infection Society reported the following figures for adults in England and Wales [Begg et al, 1999]:

Staphylococcus aureus: around 40 cases a year.

Listeria monocytogenes: around 20 cases a year.

Mycobacterium tuberculosis: around 15 cases a year.

Escherichia coli: around 10 cases a year.

Streptococcus pyogenes: around 10 cases a year.

Risk factors

What are the risk factors?

For information on the risk factors for the two main causes of bacterial meningitis, see:

What are the risk factors for meningococcal disease?

What are the risk factors for pneumococcal disease?

Meningococcal disease

What are the risk factors for meningococcal disease?

Young age is the most significant risk factor for meningococcal disease.

Although meningococcal disease can affect all ages, incidence of meningococcal disease is highest in infancy, and declines during childhood with a secondary rise in teenagers and young adults.

Meningococcal disease is the leading infectious cause of death in early childhood.

Other risk factors

The season — bacterial meningitis and meningococcal septicaemia are more prevalent during the winter, and may follow outbreaks of influenza.

Smoking, including smoking in the household.

Accommodation — including living in overcrowded households or in military barracks.

[PHLS Meningococcal Infections Working Party, 1995; Begg et al, 1999; Branco and Tasker, 2010; HPA, 2011]

Pneumococcal disease

What are the risk factors for invasive pneumococcal disease?

Risk factors for invasive pneumococcal disease (which include meningitis and bacteraemia) include [HPA, 2008; Brouwer et al, 2010; DH, 2006; Kim, 2010]:

The very young and the elderly. These groups are most at risk of invasive pneumococcal disease (with incidences exceeding 40 per 100,000 in these groups) [HPA, 2008].

An absent or non-functioning spleen.

Other cause(s) of impaired immunity (for example, HIV infection and chemotherapy).

Solid organ dysfunction (for example lung, heart, liver or kidney).

Basal skull fractures with leakage of cerebrospinal fluid.

Cochlear implants.

Nephrotic syndrome.

Sickle-cell disease.

Diabetes mellitus.

Otitis.

Sinusitis.

Incidence of invasive pneumococcal disease is highest in the winter months [HPA, 2008].

One UK study (undertaken between 1997 and 2002) reported that 76% of 50 microbiologically confirmed cases of pneumococcal meningitis in North Yorkshire were seen during the winter months [Weightman and Sajith, 2005].

Complications

What are the complications of acute bacterial meningitis?

Acute bacterial meningitis is one of the top 10 causes of infection-related death worldwide with 30–50% of survivors experiencing permanent neurological sequelae [Chaudhuri et al, 2008].

Although the mortality from acute bacterial meningitis has fallen in recent years, there has been no change in the rate of sequelae [National Collaborating Centre for Women's and Children's Health, 2010].

Global and regional risks of disabling sequelae

One recent meta-analysis (search date: 1980 to 2008, 132 studies covering 18,183 survivors of acute bacterial meningitis) calculated the median (IQR) risk of at least one major sequela to be 24.7% (95% CI 16.2–35.3%) for pneumococcal meningitis, 9.5% (95% CI 7.1–15.3%) for bacterial meningitis caused by Haemophilus influenzae type b (Hib), and 7.2% (95% CI 4.3–11.2%) for meningococcal meningitis [Edmond et al, 2010]. It also reported that:

The most common types of major sequelae were hearing loss (33·6%), followed by seizures (12·6%), motor deficit (11·6%), cognitive impairment (9·1%), hydrocephalus (7·1%), and visual disturbance (6·3%).

19.7% of people were reported to have multiple sequelae. The most common multiple impairment combinations were cognitive deficit plus hearing loss (39.1%) and cognitive deficit plus motor impairment (21.1%).

The all-cause risk of a major sequela was twice as high in African (25.1%) and Southeast Asia (21.6%) regions than in the European region (9.4%).

Prognostic factors predicting sequelae and death

In children (0 to 18 years) with bacterial meningitis, a systematic review (search date: up to March 2009, 31 studies) reported a number of prognostic factors to be statistically significant in more than one study of moderate or high quality [de Jonge et al, 2010].

These include complaints lasting more than 48 hours before admission, coma/impaired consciousness, prolonged duration of seizures, prolonged fever, shock, peripheral circulatory failure, respiratory distress, absence of petechiae, young age, and Streptococcus pneumoniae being the causative organism.

However, due to significant heterogeneity between the studies, it was not possible to determine the exact (independent) predictive values of these factors in predicting death or sequelae.

For information on the complications of the two main causes of bacterial meningitis in UK, see What are the complications of meningococcal disease? and What are the complications of pneumococcal meningitis?

Meningococcal disease

What are the complications of meningococcal disease?

In people who recover from meningococcal disease [Meningitis Research Foundation, 2008a]:

One in five experience reduced quality of life.

One in seven experience neurological or sensory disability, amputation or tissue loss, or other lifelong sequelae.

Long term complications of meningococcal disease in children and young people [SIGN, 2008; NICE, 2010a]:

Hearing loss — the most common morbidity of meningitis and meningococcal disease. Reported incidence rates ranged from 1.9–25%.

Neurological morbidities — in children, these include epilepsy, motor deficits, learning disabilities, and neurodevelopmental delay.

Bone and joint complications — these are increased with severe invasive meningococcal disease (for example damage to growth plates in children). They may only be apparent many years after the initial illness.

Skin and limb complications — meningococcal disease can cause post-necrotic scarring. Extensive soft tissue necrosis in children may require skin grafting, reconstructive surgery, or even amputation.

Renal impairment or failure.

Pneumococcal meningitis

What are the complications of pneumococcal meningitis?

The burden of sequelae remains high with pneumococcal meningitis in developed countries.

This was highlighted in a meta-analysis (search date: September 1991 to June 2009, 63 studies covering 3408 pneumococcal meningitis survivors in high-income countries) [Jit, 2010]:

The pooled prevalence of any reported sequelae was 31.7% (95% CI 27.2 to 36.3%, 47 studies).

The pooled prevalence were calculated for the following sequelae: hearing loss 20.9% (95% CI 17.1 to 24.7), seizures 6.5% (95% CI 3.3 to 9.7%), hydrocephalus 6.8% (95% CI 3.3 to 10.2%), spasticity/paresis 8.7% (95% CI 6.4 to 11.0%), cranial nerve palsies 12.2% (95% CI 5.3 to 19.1%), and visual impairment 2.4% (0 to 5.7%).

The authors warn that publication bias may result in some studies including certain sequelae under broader categories (such as neurological deficits) or not reporting certain types of sequelae.

Prognosis

What is the prognosis of acute bacterial meningitis?

Acute bacterial meningitis is a medical emergency.

It is one of the top 10 causes of infection-related death worldwide with 30–50% of survivors experiencing permanent neurological sequelae (see Complications) [Chaudhuri et al, 2008].

Table 1 highlights the incidence of and mortality from bacterial meningitis in children under 16 years of age in England and Wales.

Pneumococcal meningitis is associated with a poorer outcome than those caused by Neisseria meningitidis and Haemophilus influenzae type b (Hib) [Saez-Llorens and McCracken, 2003].

In neonates, data from a UK national surveillance study of bacterial meningitis (conducted in 1996 to 1997) reported a case fatality rate of 10% (in bacteriological proven cases) [Holt et al, 2001].

For adults in England and Wales, one study reported that mortality rates (period 1991 to 2002) among meningococcal and pneumococcal infections have fallen (from 0.45 per 100,000 to 0.31 per 100,000, p < 0.001), even though the incidence rates for these infections have not fallen [Gjini et al, 2006].

For information on the prognosis of the two main causes of acute bacterial meningitis in UK, see What is the prognosis for meningococcal disease? and What is the prognosis for pneumococcal meningitis?

Table 1 . Incidence of and mortality from bacterial meningitis in children aged under 16 years in England and Wales by causative organism.
Organism (Period of data collection, source of isolate) Number of cases Number of deaths (Case fatality rate %)
Neisseria meningitidis* (Mid 2006 to mid 2007, all invasive) 790 (aged less than 16 years; includes 38 cases in infants under 3 months). 25 (3.2%)
Streptococcus pneumoniae (2005, meningitis: cerebrospinal fluid/blood) 232 (aged less than 15 years; includes 9 cases in infants under 2 months). n/a (6% to 11%) Varies by age and is an amalgamation of data from 1998 to 2005
Haemophilus influenzae type b (Hib)* (Mid 2006 to mid 2007, all invasive) 53 (aged less than 15 years; includes 6 cases in infants under 3 months). 1 (1.9%)
* Data from Health Protection Agency. † Data from [Johnson et al, 2007].
Data from: [National Collaborating Centre for Women's and Children's Health, 2010]

Meningococcal disease

What is the prognosis of meningococcal disease?

Urgent treatment is required as meningococcal disease can rapidly be fatal, with the majority of deaths occurring in the first 24 hours (before specialist intervention).

Death is usually caused by shock and circulatory collapse (septicaemia and/or meningitis) or raised intracranial pressure (meningitis)

Septicaemia can progress rapidly to shock and circulatory collapse. Deterioration can be rapid and irreversible [Meningitis Research Foundation, 2008b].

Septicaemia is more common and is more dangerous — particularly when presenting on its own without clinical meningitis. People presenting with septicaemia only have the worst prognosis.

In children

The mortality of meningococcal disease remains high at around 10%. It is the leading infectious cause of death in children.

Septicaemia without signs of meningitis can have a mortality rate as high as 50%.

Features which predict poor prognosis at the time of presentation [Meningitis Research Foundation, 2010]:

Presence of shock.

Absence of meningism.

Rapidly progressive purpuric rash.

Low peripheral white blood cell count.

Thrombocytopenia.

Markedly deranged coagulation.

Depressed conscious level.

Pneumococcal meningitis

What is the prognosis of pneumococcal meningitis?

People with pneumococcal meningitis can deteriorate rapidly and this can be difficult to predict [Weisfelt et al, 2006].

Mortality can range from 16% to 37%.

On hospital admission, they are likely to present with focal neurological deficits (29 to 42%) and seizures (7 to 21%). Around 11-19% may presented in a comatose state.

Systemic compromise (such as hypotension and tachycardia) is an important predictor of unfavourable outcome.

In an UK study undertaken in the North Yorkshire (between 1997 and 2002), 50 cases of microbiologically confirmed cases of pneumococcal meningitis were reported with an overall in-hospital mortality of 28% [Weightman and Sajith, 2005].

Diagnosis

Diagnosis of bacterial meningitis and meningococcal septicaemia

Clinical features

What are the clinical features of bacterial meningitis or meningococcal disease?

It is not possible to rule in or rule out a diagnosis of bacterial meningitis or meningococcal disease on the basis of the presence or absence of any single clinical feature or combination of clinical features. Clinical judgement is required, taking into account how quickly the illness is progressing, the overall severity of the illness, and the level of concern on the part of the patient, parent, or carer (particularly compared with previous illness in the child or young person or their family).

Non-specific features

Common

Fever — not always present, especially in neonates.

Vomiting/nausea.

Lethargy.

Irritable or unsettled mood.

Ill appearance.

Refusal of food and drink.

Headache.

Muscle ache or joint pain.

Respiratory symptoms and signs, or difficulty breathing.

Less common

Chills or shivering

Diarrhoea, abdominal pain or distention.

Sore throat or coryza, or other ear, nose and throat symptoms or signs.

More specific features:

Stiff neck.

Altered mental state — includes confusion, delirium and drowsiness, and impaired consciousness.

Non-blanching rash — be aware that the rash may be less visible in people with darker skin tones — check soles of feet, palms of hands, and conjunctivae. For further information, see Features of meningococcal rash.

Shock (see Features of shock for further information).

Back rigidity.

Bulging fontanelle — in children younger than 2 years of age.

Photophobia.

Kernig's sign — when the thigh is flexed onto the abdomen, check whether the leg can be passively extended when the knee is flexed. Meningeal inflammation will cause the person to resist leg extension (positive Kernig's sign).

Brudzinski's sign — when passive flexion of the neck is performed, meningeal irritation will result in flexion of the hips and knees (positive Brudzinski's sign).

Unconsciousness.

Toxic or moribund state.

Paresis.

Focal neurological deficit, including cranial nerve involvement and abnormal pupils.

Seizures.

In a person presenting only with meningococcal septicaemia, Kernig's sign, Brudzinski's sign, paresis, focal neurological deficit, and seizures are not present.

Features of shock

Signs of shock

In their guideline on acute bacterial meningitis and meningococcal septicaemia, the National Institute for Health and Care Excellence highlights the following features of shock [NICE, 2010a]:

Capillary refill time more than 2 seconds.

For further information on capillary refill time, see Normal physiological values under Assessment of vital signs.

Unusual skin colour (such as skin mottling).

Tachycardia and/or hypotension.

Respiratory symptoms or breathing difficulty.

Leg pain.

Cold hands or feet.

Toxic or moribund state.

Altered mental state or decreased conscious level.

Poor urine output.

Basis for recommendation

Basis for recommendation

These recommendations are based on the clinical guideline, Bacterial meningitis and meningococcal septicaemia, published by the National Institute for Health and Care Excellence (NICE) [National Collaborating Centre for Women's and Children's Health, 2010]. They are based on expert opinion and limited evidence. Where appropriate, CKS has extrapolated these recommendations for children and young people to adults.

Clinical features of bacterial meningitis, meningococcal disease, and meningococcal septicaemia

The NICE guidance development group (GDG) evaluated the evidence on:

The prevalence of individual signs and symptoms of bacterial meningitis (three prospective cohort studies, nine retrospective studies [of which eight were cohort studies], and one cross-sectional study).

Symptoms and signs of bacterial meningitis compared to those of viral or aseptic meningitis (two cohort studies).

Symptoms and signs of meningococcal septicaemia (a systematic review of mainly descriptive studies, three prospective cohort studies, and six retrospective case series — however, only one study specifically reported symptoms and signs of meningococcal septicaemia [see below]).

However, the NICE GDG highlighted a number of serious weaknesses in the evidence:

Most of the reported data did not distinguish clearly between symptoms and signs of meningococcal septicaemia, meningococcal meningitis, and other bacterial causes of meningitis.

Most of the studies were retrospective.

No studies were identified by NICE which provided frequencies of clinical features in children with bacterial meningitis before admission to hospital.

Studies of clinical features noted at or during hospital admission were limited in quality because:

In all cases, it was not possible to calculate sensitivity or specificity of the clinical features identified.

There were variations between the studies regarding the type of bacterial meningitis, stage of the illness presented, type of hospital setting, and country.

These studies are likely to be biased as only children who were clinically suspected to have meningitis (such as neck stiffness) would be selected for investigation (for lumbar puncture).

For meningococcal disease, the diagnostic accuracy of symptoms and signs (individually or in combination) in primary and secondary care settings were not reported in most studies.

Based on the evidence evaluated and expert opinion, the GDG produced an overview of symptoms and signs that should lead healthcare professionals to consider a diagnosis of bacterial meningitis, meningococcal disease and meningococcal septicaemia.

For meningococcal septicaemia, these clinical features were extrapolated from meningococcal disease data. This was necessary as only one study identified reported symptoms and signs specifically for meningococcal septicaemia, whereas several studies provided prevalence data for children and young people with meningococcal disease.

The lack of diagnostic clinical features has also been highlighted in two recent systematic reviews:

In a systematic review of prospective data (search date up to June 2009, 10 papers met inclusion criteria), several useful clinical features were found to influence the likelihood of bacterial meningitis in children [Curtis et al, 2010]. However, no isolated clinical feature was found to be diagnostic and the most accurate diagnostic combination remain unclear.

In another systematic review examining which clinical features can be used to confirm or exclude the possibility of serious infection in children presenting to ambulatory care settings in developed countries (search date: up to June 2009, 30 studies met inclusion criteria with 3 retrospective studies involving children with meningitis), no clinical features were found to have a rule-out value but some combinations of clinical features can be used to exclude the possibility of serious infection (but not specifically for meningitis) [Van den Bruel et al, 2010]. Although red flags for serious infection were identified (such as rapid breathing, poor peripheral perfusion, and petechial rash), the authors warn that serious illness will still be missed without effective use of precautionary measures.

Difficulty in diagnosing meningococcal disease

NICE and the Scottish Intercollegiate Guidelines Network (SIGN) highlighted the reasons why the diagnosis of meningococcal disease is a challenge in primary care [SIGN, 2008; National Collaborating Centre for Women's and Children's Health, 2010]:

The disease is rare (see Prevalence in Background information). Most healthcare professionals will only encounter one or two cases in their entire career. Consequently, most will have difficulty gaining experiencing in recognizing the disease.

In the early stages of meningococcal disease, clinical features may be vague and non-specific and are similar to other non-bacterial cases of meningitis (see Differential diagnosis) and to many common, less life-threatening viral illnesses. Although many unwell children will present with a fever, very few will develop meningococcal disease. The classic presentation of meningococcal disease is uncommon in primary care.

The obvious features of meningococcal disease may take time to emerge. Unfortunately, the disease can progress very rapidly, with most children being admitted to hospital within about 24 hours of the illness starting. Consequently, this leaves little time for healthcare professionals to 'wait and see' if clinical features are evolving.

The frequency of clinical features varies between children of different ages.

There is a lack of community-based studies which have investigated the frequency of symptoms and signs suggestive of meningococcal disease.

The Meningitis Research Foundation highlighted meningococcal disease as very unpredictable. In its guidance for doctors in training, it warned to avoid simply 'eyeballing' a child and assuming they have a trivial illness, as this how many mistakes are made [Meningitis Research Foundation, 2010].

The diagnosis of meningococcal disease can only be confirmed in secondary care [National Collaborating Centre for Women's and Children's Health, 2010]. The definitive test for meningitis is a lumbar puncture with laboratory examination of the cerebrospinal fluid.

Features of meningococcal rash

How should I assess a rash that is suspicious of meningococcal septicaemia?

People with meningococcal meningitis or meningococcal septicaemia may develop a blanching or a non-blanching rash. Be aware that:

The process of meningitis or septicaemia can be quite advanced before the rash starts to appear.

A blanching rash may develop into a non-blanching rash as the illness progresses.

When a non-blanching rash is present, it may appear as either as a purpuric rash and/or petechial rash. A rapidly evolving petechial or purpuric rash is a sign of very severe disease.

Purpuric (haemorrhagic) rash (spots larger than 2 mm in diameter)

Some children and young people with meningococcal septicaemia will develop a haemorrhagic rash, but this may be absent in the pre-hospital phase of the illness and may initially be blanching or macular in nature.

Scanty petechial rash

Petechiae are red or purple non-blanching macules smaller than 2 mm in diameter. Consequently, the rash may appear as 'flea bitten'.

Although it can indicate the presence of serious bacterial infection (in particular, with Neisseria meningitidis), the majority of children and young people with petechial rashes seen in primary care and Accident and Emergency departments do not have meningococcal disease.

Be aware that petechial rashes can be caused by infections other than meningococcal disease and also by non-infective causes (see Other causes of petechial rashes).

Images of petechial, purpuric, and meningococcal rashes can be found in the document Recognition and early management of meningococcal disease in children and young people (pdf) (see pages 52–54) produced by the Meningitis Research Foundation (available at www.meningitis.org).

Images of meningococcaemia are also available on www.dermnet.com/Meningococcemia.

The risk of meningococcal disease is high in a child or young person with petechiae if:

The petechiae start to spread

The rash becomes purpuric

There are signs of bacterial meningitis

There are signs of meningococcal septicaemia

The child or young person appears ill to a healthcare professional.

Meningococcal disease is less likely in an afebrile child or young person (or one with a history of fever) who is presenting with a non-spreading petechial rash — especially if the rash has been present for more than 24 hours.

Examine the whole body systematically for rash and unusual skin colour — particularly for non-blanching rashes and petechiae. It can some time to make a careful assessment.

This is best performed:

Under good lighting, checking the whole body (particularly in a febrile child with no focal cause).

While the child is not crying (if possible). This can be difficult to perform in neonates and infants as they can be uncooperative when ill and it is often difficult to pinpoint where the infection is coming from.

Non-blanching rash can be checked using the 'glass test'.

This involves pressing the side of a glass or tumbler firmly against the rash to see if the rash fades or loses colour under pressure. A petechial or purpuric rash does not fade.

Be aware that the glass test should not be used solely for diagnosing bacterial meningitis and meningococcal septicaemia. The glass test should only used as an aid to determine whether a rash blanches under pressure.

For people with darker skin, a rash may be less visible (even when using the glass test). Check paler areas of the body (such as the soles of the feet or palms of the hands) or the conjunctivae or palate.

Ask the parent or person about any new rashes or marks (such as a bruise, spot, blister, or stain — the person may use other words to describe a rash).

Other causes of petechial rashes

Other causes of petechial rashes

In addition to meningococcal infection, petechiae may have other causes, such as [Forgie and Marrie, 2010]:

Other infections — for example enterovirus, Epstein-Barr virus, adenoviruses, and respiratory viruses.

Non-infective causes — these include clotting factor or platelet deficiencies. Petechiae in the eyes or on the face may also result from non-infective causes (such as sneezing, coughing, vomiting, and trauma).

Basis for recommendation

Basis for recommendation

These recommendations are based on the clinical guideline Bacterial meningitis and meningococcal septicaemia published by the National Institute for Health and Care Excellence (NICE) [National Collaborating Centre for Women's and Children's Health, 2010], guidance from the Meningitis Research Foundation endorsed by the British Medical Association [Meningitis Research Foundation, 2008a] and by the Royal College of Paediatrics and Child Health and College of Emergency Medicine [Meningitis Research Foundation, 2010]), and expert narrative reviews on meningococcal disease [Hart and Thomson, 2006], on petechiae [Forgie and Marrie, 2010], and on the glass test [Parikh and Maconochie, 2003; Mant and Van den Bruel, 2010].

Petechiae and purpura

A variety of rashes may occur in any type of meningitis. Petechial and purpuric rashes are usually indicative of invasive meningococcal infection (although they can be present in Haemophilus influenzae type b meningitis and pneumococcal disease) [Begg et al, 1999; Saez-Llorens and McCracken, 2003].

Petechiae and purpura are significantly more common with invasive meningococcal infection than with pneumococcal meningitis (which rarely presents with rashes).

The non-blanching rash is caused by the presence of meningococcal endotoxin in the blood stream. This causes the monocytes and neutrophils to produce pro-inflammatory cytokines which alter coagulation and lead to endothelial cell injury. The net result is blood and other fluid leaking out of the damaged blood vessels into the surrounding tissues. This occurs in all the small blood vessels in the body and is most visible in the skin [Forgie and Marrie, 2010; Meningitis Research Foundation, 2010].

Glass test

Although the glass test is widely promoted in patient information leaflets, CKS found no evidence on its use. The glass test is not promoted in the NICE or Scottish Intercollegiate Guidelines Network (SIGN) guidelines [SIGN, 2008; NICE, 2010a].

Two expert reviews highlighted the dangers of relying solely on this test for the diagnosis of meningococcal disease [Parikh and Maconochie, 2003; Mant and Van den Bruel, 2010]. This is because of the risk of getting a:

False-negative result — as the haemorrhagic rash may be absent in the pre-hospital phase and may initially be blanching or macular in nature.

False-positive result — most people with petechial rashes seen in primary care and Accident and Emergency departments do not have meningococcal disease. In addition, petechial rashes may be caused by other infections and non-infective causes (see Other causes of petechial rashes).

Consequently, the glass test should not be used as the only test for diagnosing meningococcal meningitis and/or meningococcal septicaemia.

Presentation in a child or young person

How is a child or a young person with bacterial meningitis or meningococcal disease likely to present?

In children and young people with bacterial meningitis or meningococcal disease, the disease is not always obvious.

With bacterial meningitis

Bacterial meningitis can evolve rapidly.

Non-specific features of infection (such as fever, vomiting, irritability and upper respiratory tract symptoms) are likely to be present.

Many, but not all, children and young people will have neck stiffness or decreased level of consciousness.

A minority of children and young people will have seizures or shock.

The classic triad of meningitis (headache, neck stiffness, and photophobia) only occur in a minority of children and young people before hospital admission.

If these features are present, they are more likely to occur in older children and young people than in young children.

Older children and young people

Many, but not all, children and young people with bacterial meningitis will have neck stiffness or decreased level of consciousness.

Children younger than 2 years of age

They are more likely to present with irritability, lethargy, and decreased level of consciousness. Some will have a bulging fontanelle and neck stiffness.

Infants and neonates (younger than 28 days of age)

Infants are less likely to have clinical features of meningism (such as headache, stiff neck, or photophobia).

In neonates, it is not possible to accurately distinguish bacterial infections from trivial infections.

Although fever is a common non-specific symptom, it is more often absent in neonates.

With meningococcal disease

They can present with a wide variety of clinical features, depending on:

Their age.

The duration of the illness.

Whether they have focal infection (for example meningitis) or septicaemia.

Meningococcal disease can rapidly be fatal, with the majority of deaths occurring in the first 24 hours (before specialist care intervention).

The initial stages of meningococcal disease can be similar to those seen in minor respiratory or gastrointestinal illness (such as coryza and diarrhoea).

Most will present with relatively non-specific clinical features, such as fever, gastrointestinal symptoms (such as nausea, vomiting, and poor appetite [or poor feeding in babies]), drowsiness, and irritability.

The early (or prodromal) phase of meningococcal disease can last up to 4 hours in young children, and 8 hours in adolescents. In some cases, this can be much longer.

Be aware that fever is not present in all children (particularly in neonates) with serious bacterial infection.

Hypothermia (particularly in infants) may also indicate serious infection.

Although many children become suddenly ill with a fever, some can develop septicaemia after what seems to have been a simple viral illness.

These children may present initially with trivial symptoms which last for some time, before deteriorating with a high fever and other symptoms of sepsis.

Symptoms of meningococcal disease progresses in the following order: fever, symptoms of sepsis, haemorrhagic rash, impaired consciousness and meningism.

In the early stages of the illness, most children and young people experience pain in their extremities (which can make them restless and miserable), paleness (mottled or pallid appearance, or cyanosis), and cold extremities (despite the presence of fever). Median time of onset is around 8 hours.

In later stages, they may have an altered mental state, hypotension, and respiratory symptoms.

The classical features of haemorrhagic rash, meningism and impaired consciousness also develop later (median onset 13–22 hours).

Features which predict poor prognosis at the time of presentation include:

Presence of shock.

Absence of meningism.

Rapidly progressive purpuric rash.

Depressed conscious level.

Most children and young people with meningococcal disease will develop a haemorrhagic rash during their illness.

However, this may not be present in the pre-hospital phase of the illness.

In addition, the rash may initially be blanching or macular in nature.

For further information, see Features of meningococcal rash for further information.

Basis for recommendation

Basis for recommendation

This information is based on the following documents:

The clinical guideline Bacterial meningitis and meningococcal septicaemia published by the National Institute for Health and Clinical Excellence (NICE) [National Collaborating Centre for Women's and Children's Health, 2010]. It is derived from evidence reviewed by NICE (for further information, see Basis for recommendation in Clinical features).

The guidance Recognition and early management of meningococcal disease in children and young people issued by the Meningitis Research Foundation [Meningitis Research Foundation, 2010]. The guidance is endorsed by the Royal College of Paediatrics and Child Health and the College of Emergency Medicine.

Presentation in adults

How is an adult with bacterial meningitis likely to present?

Evidence on the presentation of bacterial meningitis (including meningococcal disease) in primary care is lacking.

Adults with bacterial meningitis typically present with clinical features of meningeal irritation. Most will present with at least two of the following:

Headache.

Fever.

Neck stiffness.

Altered mental status.

Basis for recommendation

Basis for recommendation

This information is based on the Consensus statement on diagnosis, investigation, treatment and prevention of acute bacterial meningitis in immunocompetent adults issued by the British Infection Society [Begg et al, 1999], the guideline on the management of community-acquired bacterial meningitis published by European Federation of Neurological Societies [Chaudhuri et al, 2008], and expert narrative reviews [Fitch and van de Beek, 2007; Schut et al, 2008; Brouwer et al, 2010].

For adults, evidence on the presentation of bacterial meningitis in primary care is lacking — particularly in the early stages of meningitis [Begg et al, 1999; Fitch and van de Beek, 2007].

One literature review (search date: up to July 1997; 10 studies met inclusion criteria) found many of the signs and symptoms of bacterial meningitis have been inadequately studied [Attia et al, 1999]. It reported that individual items of the clinical history have low accuracy for the diagnosis of meningitis in adults. However, it found the absence of fever, neck stiffness, and altered mental status effectively excludes bacterial meningitis (sensitivity 99–100% for the presence of one of these findings).

The British Infection Society highlights the following important points regarding acute bacterial meningitis in adults [Begg et al, 1999]:

Neck stiffness is absent in 18% of patients. Its absence does not exclude meningitis.

Skin rashes (in particular petechiae or purpura) are significantly more common in meningococcal meningitis than in pneumococcal meningitis. In addition, a variety of rashes can occur in any type of meningitis (including those in which the cultures are negative). For further information on meningococcal rashes, see Features of meningococcal rash.

Fundoscopic abnormalities are unusual (with a figure of 4% reported in one study).

Cranial nerve palsies (in particular, affecting the nerves III, IV, VI, and VII) and focal neurological signs occur in 10-30% of cases. These might be early sign of meningitis caused by Listeria monocytogenes.

85% of people are found to exhibit abnormal mental states — which may be the only sign in the elderly.

Seizures have been reported in 30% of cases and are significantly more common in pneumococcal than meningococcal meningitis.

A guideline produced by the European Federation of Neurological Societies (EFNS) on acute bacterial meningitis in older children and adults provides little information on clinical presentation [Chaudhuri et al, 2008]. It only highlighted one Dutch study involving adults with bacterial meningitis.

Based on 696 cases, this study reported the sensitivity of the classic triad of fever, neck stiffness, and altered mental status to be low (appearing in only 44% of cases) [van de Beek et al, 2004]. However, 95% of cases have at least two of the following four symptoms: headache, fever, neck stiffness, and altered mental status.

Assessment of vital signs

How should I assess vital signs in a person with suspected bacterial meningitis or meningococcal disease?

In all people with suspected bacterial meningitis or meningococcal disease:

Check and document the following:

Heart rate.

Respiratory rate.

Blood pressure.

Temperature.

Capillary refill time.

Oxygen saturation (if a pulse oximeter is available).

See Normal physiological values for reference values, and the section on Features of shock under Clinical features.

Perform a neurological assessment — for example, using the Alert, Voice, Pain, Unresponsive (AVPU) scale:

Is the person Alert? (Be aware that a very ill child with septicaemia can still be alert.)

Does the person respond to your Voice?

Does the person respond to Pain?

Is the person Unresponsive?

Normal physiological values

Capillary refill time:

This can be assessed by pressing for 5 seconds on the nail of the big toe or finger, the forehead, or the centre of the sternum until it blanches. Count the time (in seconds) it takes for the colour to return.

In the guideline on acute bacteria meningitis and meningococcal septicaemia, the National Institute for Health and Care Excellence (NICE) advised that a capillary refill time more than 2 seconds to be one of the signs for shock (see Features of shock under Clinical features) [NICE, 2010a].

Oxygen saturation:

For children and young adults, the normal value is greater than 95% in air.

The normal ranges for heart rate, respiratory rate, and systolic blood pressure for children and young people are outlined in Table 1.

Table 1 . Normal range for various vital signs for children and young people.
Age (years) Heart rate (per minute) Respiratory rate (per minute) Systolic blood pressure
Younger than 1 year 110–160 30–40 70–90
1–2 years 100–150 25–35 80–95
2–5 years 95–140 25–30 80–100
5–12 years 80–120 20–25 90–110
Older than 12 years 60–100 15–20 100–120
Data from: [Meningitis Research Foundation, 2008a; Meningitis Research Foundation, 2010]

[Meningitis Research Foundation, 2008a; Meningitis Research Foundation, 2010]

Basis for recommendation

Basis for recommendation

These recommendations are based on the clinical guideline Bacterial meningitis and meningococcal septicaemia published by the National Institute for Health and Care Excellence (NICE) [National Collaborating Centre for Women's and Children's Health, 2010], and guidance from the Meningitis Research Foundation endorsed by the British Medical Association [Meningitis Research Foundation, 2008a] and by the Royal College of Paediatrics and Child Health and the College of Emergency Medicine [Meningitis Research Foundation, 2010]).

Differential diagnosis

What else might it be?

Bacterial meningitis, meningococcal disease or meningococcal septicaemia should be assumed in all people presenting with clinical features consistent with these infections until proven otherwise.

The differential diagnosis of acute bacterial meningitis is very difficult, as the illnesses can present with many common non-specific clinical features. These features are also found in other non-life-threatening, self-limiting infections, as well as other forms of infective and non-infective causes of meningitis.

Differential diagnosis of acute bacterial meningitis include:

Other infective meningitis and meningoencephalitis (viral, tuberculous, fungal, leptospiral, and primary amoebic) — for example:

Viral meningitis

This is common and can occur at any age. It is not possible to differentiate viral and bacterial meningitis with any certainty on the basis of clinical features alone.

However, unlike bacterial meningitis which can be life-threatening if left untreated, viral meningitis is usually a less serious disease with spontaneous recovery. Confusion and seizures are very rare in cases of viral meningitis (except for febrile convulsions in small children).

Enteroviruses (for example Coxsackie A and B viruses, and echoviruses) are the most common cause of viral meningitis in children and adults. Management is generally conservative. Most cases presenting clinically with meningitis are self-limiting with a good prognosis. However, enteroviral meningitis can lead to meningoencephalitis.

Other causes of viral meningitis include the herpes simplex virus (HSV) (usually a complication of primary genital herpes [especially with HSV-2] in adults and adolescents and is self limiting in immunocompetent people) and the Human immunodeficiency virus (HIV) (neurological conditions [such as meningitis, meningoencephalitis, and encephalitis] may be associated with more rapid progression of HIV-related disease).

Fungal meningitis

Although life-threatening, fungal meningitis is rare. People at risk of fungal meningitis are those with immunodeficiency (for example people with AIDS) or with immunosuppression (for example caused by chemotherapy).

Cryptococcus is the most common cause of fungal meningitis in immunocompromised people.

Tuberculous meningitis

Some features of tuberculous meningitis are indistinguishable from acute bacterial meningitis.

Viral encephalitis.

Certain cancers and central nervous system tumours.

Brain abscess.

Spinal epidural abscess (cervical).

Parameningeal infection — such as cranial osteomyelitis and subdural empyema.

Other non-infective causes of meningitis

Autoimmune disorders, for example systemic lupus erythematosus, Behçet's syndrome.

Drugs:

Aseptic meningitis is a rare adverse drug reaction and seems to be associated with connective tissue disease (in particularly systemic lupus erythematosus).

A variety of drugs have been reported as causing meningitis, mainly on the basis of anecdotal reports. Nonsteroidal anti-inflammatory drugs have been most commonly implicated (with ibuprofen most reported).

Basis for recommendation

Basis for recommendation

This information is based on expert reviews [Seaton and France, 1999; Newton et al, 2002; Hopkins and Jolles, 2005; Logan and MacMahon, 2008; Schut et al, 2008; Branco and Tasker, 2010], case reports of drug-induced meningitis [Seaton and France, 1999; Tamburini et al, 2005; Rodriguez et al, 2006], a European guideline on managing community-acquired bacterial meningitis [Chaudhuri et al, 2008], and the clinical guideline Bacterial meningitis and meningococcal septicaemia published by the National Institute for Health and Care Excellence (NICE) [NICE, 2010a].

CKS identified no guidance or reference to allow primary care healthcare professionals to distinguish these conditions reliably.

Management

Management

Scenario: Non-blanching rash or meningococcal septicaemia : covers the pre-hospital management of suspected bacterial meningitis with non-blanching rash or meningococcal septicaemia.

Scenario: Without non-blanching rash : covers the pre-hospital management of suspected bacterial meningitis without non-blanching rash.

Scenario: Managing close contacts : covers the management of people who have been in close contact with a person who has been confirmed as having pneumococcal or meningococcal disease.

Scenario: Follow up after discharge : covers the follow up of people who have recovered from bacterial meningitis or meningococcal septicaemia, after they have been discharged from hospital.

Scenario: Non-blanching rash or meningococcal septicaemia

Scenario: Managing suspected bacterial meningitis with non-blanching rash or meningococcal septicaemia

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Management

How should I manage a person presenting with suspected bacterial meningitis with a non-blanching rash or meningococcal septicaemia?

If there is any clinical suspicion of bacterial meningitis with non-blanching rash or meningococcal septicaemia (see Diagnosis for further information on clinical features of these conditions including features of meningococcal rash):

Admit the person as an emergency by telephoning 999.

Administer a single dose of parenteral benzylpenicillin at the earliest opportunity, provided that treatment does not delay urgent transfer to hospital.

Ideally, benzylpenicillin should be given intravenously, or intramuscularly if a vein is not available.

If given intramuscularly, it should be given as proximally as possible — preferably into a part of the limb that is still warm (as cold areas will be less well perfused).

Dosage:

Adults and children 10 years of age or older — 1200 mg.

Children 1–9 years of age — 600 mg.

Children younger than 1 year of age — 300 mg.

Benzylpenicillin should be carried in GP emergency bags, and checked regularly to ensure that it is within its expiry date.

Withhold benzylpenicillin if the person has a clear history of penicillin anaphylaxis (a history of a rash following penicillin is not a contraindication).

Basis for recommendation

Basis for recommendation

These recommendations are based on the clinical guideline Bacterial meningitis and meningococcal septicaemia published by the National Institute for Health and Care Excellence (NICE) [NICE, 2010a], the clinical guideline Management of invasive meningococcal disease in children and young people published by the Scottish Intercollegiate Guidelines Network (SIGN) [SIGN, 2008], and the Guidance for public health management of meningococcal disease in the UK published by the Health Protection Agency [HPA, 2011].

Urgent hospital admission for children and young people

The NICE guidance development group (GDG) recommends urgent hospital admission (as an emergency by telephoning 999) for children and young people with suspected bacterial meningitis with non-blanching rash or meningococcal septicaemia [NICE, 2010a]. This is because a delay in transfer to secondary care is associated with poor outcome [National Collaborating Centre for Women's and Children's Health, 2010].

A similar recommendation is made by SIGN, who also emphasized that, if a diagnosis is of meningococcal disease is likely, urgent treatment should not be delayed with interval assessment [SIGN, 2008].

Given that it is not possible to distinguish these two conditions, suspected meningococcal disease should be assumed if a non-blanching rash is present [National Collaborating Centre for Women's and Children's Health, 2010; NICE, 2010b]. This is also in line with recommendation from:

The SIGN guideline which stated that: 'generalised petechial rash, beyond the distribution of the superior vena cava, or a purpuric rash in any location, in an ill child, are strongly suggestive of meningococcal septicaemia and should lead to urgent treatment and referral to secondary care' [SIGN, 2008]. A petechial rash is one of the features in an ill child which 'should prompt consideration of a diagnosis of invasive meningococcal disease' [SIGN, 2008].

A guideline issued by The European Federation of Neurological Societies (EFNS) on the management of community-acquired bacterial meningitis in older children and adults [Chaudhuri et al, 2008].

Expert narrative reviews [Forgie and Marrie, 2010].

For further information on meningococcal rashes, see Features of meningococcal rash in Diagnosis.

Urgent hospital admission for adults

The scope of the NICE and SIGN clinical guidelines is limited to children and young people. Urgent hospital admission is also recommended for adults by the following guidance:

The Health Protection Agency's guidance for public health management of meningococcal disease, which stressed that 'rapid admission to hospital is highest priority when meningococcal disease is suspected' [HPA, 2011].

The European Federation of Neurological Societies (EFNS) guidance on managing community-acquired bacterial meningitis in older children and adults [Chaudhuri et al, 2008].

Guidance on meningococcal meningitis and septicaemia issued by the Meningitis Research Foundation, and endorsed by the British Medical Association [Meningitis Research Foundation, 2008a].

Guidance from the Chief Medical Officer (CMO) [CMO, 1999], a Public Health Laboratory Services (PHLS) guidance on the control of meningococcal disease for consultants in communicable disease control [PHLS Meningococcal Infections Working Party, 1995], and a consensus statement from the British Information Society Working Party on the diagnosis, investigation, treatment and prevention of acute bacterial meningitis in immunocompetent adults [Begg et al, 1999].

Given that it is not possible to accurately differentiate bacterial meningitis from other causes (for example viral meningitis), experts recommend that all suspected cases of acute meningitis should be admitted urgently for confirmation of diagnosis and ongoing management [Logan and MacMahon, 2008].

Pre-hospital parenteral antibiotics

There is a lack of good trial evidence to support the use of pre-hospital antibiotic treatment.

The NICE GDG's recommendation to give pre-hospital parenteral antibiotics to children and young people with suspected meningococcal disease is based on recommendations from the Chief Medical Officer (CMO) [CMO, 1997; National Collaborating Centre for Women's and Children's Health, 2010]. They found no evidence to support the CMO recommendation.

The CMO advised the following for all suspected cases of meningococcal disease (all ages) [CMO, 1997]:

Benzylpenicillin should be given as soon as the diagnosis of meningococcal infection (especially in the presence of fever and a haemorrhagic rash and accompanied by altered consciousness) is suspected, if possible given intravenously.

Benzylpenicillin should be withheld only in individuals if there is a known history of anaphylaxis following previous penicillin administration; a history of rash following penicillin is not a contraindication.

The NICE GDG found no evidence to recommend an alternative to benzylpenicillin [National Collaborating Centre for Women's and Children's Health, 2010].

Pre-hospital antibiotic treatment is also recommended in guidance issued by SIGN, HPA, and EFNS [Chaudhuri et al, 2008; SIGN, 2008; HPA, 2011].

Although the NICE GDG found no evidence to direct a change in practice, they considered that a strong recommendation to give antibiotics in the community could lead to delayed hospital admittance. Given that the priority is to prevent death, the consensus view of the GDG is that 'parenteral antibiotics should be administered as early as practicable in people with meningococcal disease but the priority in clinical management should be immediate access to hospital care' [National Collaborating Centre for Women's and Children's Health, 2010].

This NICE recommendation is also highlighted in the updated HPA guidance on managing meningococcal disease in children and adults [HPA, 2011].

Benzylpenicillin dosage and route of administration

The dosages of benzylpenicillin are in line with guidance issued by the Chief Medical Officer, NICE, the HPA, the Meningitis Research Foundation, the British Infection Society, the PHLS, and SIGN, as well as by the manufacturer of benzylpenicillin [PHLS Meningococcal Infections Working Party, 1995; Begg et al, 1999; CMO, 1999; Meningitis Research Foundation, 2008a; SIGN, 2008; NICE, 2010a].

Although NICE recommended that benzylpenicillin can be given intramuscularly or intravenously [NICE, 2010a], the preferred route of administration is by intravenous injection [PHLS Meningococcal Infections Working Party, 1995; Rajapaksa and Starr, 2010]. However, this might be difficult if the person's circulatory system is compromised (for example if they are in shock due to reduced tissue perfusion).

Intramuscular injection is the less preferred as drug absorption can be impaired by shock and hypotension. However, it is recommended if a vein cannot be found [PHLS Meningococcal Infections Working Party, 1995], as this is preferable to giving no antibiotics [Rajapaksa and Starr, 2010].

Alternative pre-hospital parenteral antibiotic in people with penicillin allergy

Both NICE and SIGN do not recommended specific parenteral antibiotics for children or young people who have a clear history of penicillin anaphylaxis [SIGN, 2008; NICE, 2010a]. The priority is urgent transfer to hospital.

In line with the NICE guideline, the updated HPA guidance (published in January 2011) no longer recommends alternative antibiotics for people with penicillin allergy [HPA, 2011].

This is a change from the previous HPA guidance which recommended pre-hospital administration of chloramphenicol (off-label use) for people with a history of immediate allergic reactions after previous penicillin or cephalosporin administration [HPA, 2006]. This recommendation is in line with an earlier PHLS guidance on the control of meningococcal disease (chloramphenicol dose: 1.2 g for adults and 25mg/kg for children under 12 years, ideally intravenously or intramuscularly if a vein is not available) [PHLS Meningococcal Infections Working Party, 1995].

As highlighted by some CKS external reviewers, chloramphenicol is rarely carried in GP emergency bags.

Chloramphenicol is still recommended by the British National Formulary if there is a history of immediate hypersensitivity reaction to penicillin or to cephalosporins [BNF 60, 2010]. No explicit information is given regarding pre-hospital dosage or the basis to support this recommendation. For information on BNF dosages, see Pre-hospital antibiotic treatment in Scenario: Without non-blanching rash.

Scenario: Without non-blanching rash

Scenario: Managing suspected bacterial meningitis without non-blanching rash

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Management

How should I manage a person presenting with suspected bacterial meningitis without non-blanching rash?

If there is any clinical suspicion of bacterial meningitis without non-blanching rash (for information on the clinical features of bacterial meningitis, see Diagnosis):

Admit the person as an emergency by telephoning 999.

Do not give any parenteral antibiotic treatment unless urgent transfer to hospital is not possible (for example in remote locations or owing to adverse weather conditions).

For further information regarding antibiotic choice, see Pre-hospital antibiotic treatment.

If the person has no specific clinical features of bacterial meningitis, but it is not possible to exclude the person being in the early stages of the disease:

Consider watchful waiting and offer safety netting.

For further information, see Safety netting.

Basis for recommendation

Basis for recommendation

These recommendations are based on the clinical guideline Bacterial meningitis and meningococcal septicaemia published by the National Institute for Health and Care Excellence (NICE) [NICE, 2010a], and the clinical guideline Management of invasive meningococcal disease in children and young people published by the Scottish Intercollegiate Guidelines Network (SIGN) [SIGN, 2008].

Urgent hospital admission for children and young people

The NICE guidance development group (GDG) recommend urgent hospital admission (as an emergency by telephoning 999) for children and young people with suspected bacterial meningitis without non-blanching rash [NICE, 2010a].

With bacterial meningitis and meningococcal disease, urgent hospital admission is recommended because a delay in transfer to secondary care is associated with poor outcome [National Collaborating Centre for Women's and Children's Health, 2010].

A similar recommendation is made by SIGN, who also emphasize that, if the diagnosis is of meningococcal disease (which include meningococcal meningitis by itself) is likely, urgent treatment should not be delayed with interval assessment [SIGN, 2008].

Urgent hospital admission for adults

The scope of the NICE and SIGN clinical guidelines is limited to children and young people. Similar recommendations are made for adults by the following guidance:

A guideline issued by The European Federation of Neurological Societies (EFNS) on the management of community-acquired bacterial meningitis in older children and adults [Chaudhuri et al, 2008]. Immediate transfer to the nearest secondary care centre is recommended for those people with suspected acute bacterial meningitis 'without rapidly evolving skin rash.'

The Health Protection Agency's guidance for public health management of meningococcal disease, which stresses that 'rapid admission to hospital is highest priority when meningococcal disease is suspected' [HPA, 2011].

Guidance on meningococcal meningitis and septicaemia issued by the Meningitis Research Foundation, and endorsed by the British Medical Association [Meningitis Research Foundation, 2008a].

Guidance on meningococcal infection from the Chief Medical Officer (CMO) [CMO, 1999]; a Public Health Laboratory Services (PHLS) guidance on the control of meningococcal disease for consultants in communicable disease control [PHLS Meningococcal Infections Working Party, 1995]; and a consensus statement from the British Information Society Working Party on the diagnosis, investigation, treatment, and prevention of acute bacterial meningitis in immunocompetent adults [Begg et al, 1999].

Given that it is not possible to accurately differentiate bacterial meningitis from other causes (for example viral meningitis), experts recommend that all suspected cases of acute meningitis should be admitted urgently for confirmation of diagnosis and ongoing management [Logan and MacMahon, 2008].

Pre-hospital parenteral antibiotics in people with suspected meningitis without non-blanching rash

For children and young people with suspected meningitis without non-blanching rash, the NICE GDG did not recommend giving parenteral antibiotics (unless urgent transfer to hospital is not possible) because [National Collaborating Centre for Women's and Children's Health, 2010]:

It found no high-quality evidence on the effects of pre-hospital antibiotics in children and young people with suspected bacterial meningitis.

It highlights that it is usual to administer antibiotics in hospital than in primary care for these people. This is because:

The rate of progression of the disease is slower when compared with septicaemia.

Lumbar puncture is usually performed before antibiotic administration. If lumbar puncture is not performed, it is difficult to distinguish bacterial meningitis from other illnesses which do not require antibiotic treatment.

Corticosteroids are used as adjunctive therapy for bacterial meningitis, and these should be administered before or with the first dose of antibiotics.

Consequently, antibiotic treatment should be delayed until the diagnosis has been made by lumbar puncture in secondary care.

The NICE GDG found no evidence to direct a change in practice.

This recommendation is in line with the following guidance (which also applies to adults):

The EFNS guideline on managing community-acquired bacterial meningitis in older children and adults [Chaudhuri et al, 2008]. If there is no 'strong suspicion of disseminated meningococcal infection (meningococcemia)', they recommend that 'rapid preadmission antibiotic therapy should be considered only if a delay in excess of 90 minutes in hospital transfer is anticipated' [Chaudhuri et al, 2008]. Immediate transfer to the nearest secondary care centre is recommended for suspected acute bacterial meningitis 'without rapidly evolving skin rash'.

Guidance for ambulance personnel issued by the Meningitis Research Foundation and endorsed by the Joint Royal Colleges Ambulance Liaison Committee (JRCALC) [Meningitis Research Foundation, 2008b]. The guidance only recommends giving benzylpenicillin to people with clinical features indicative of meningococcal septicaemia if a non-blanching rash is present.

Pre-hospital antibiotic treatment

What pre-hospital antibiotic treatment is recommended for people with suspected bacteria meningitis without a non-blanching rash?

For people with suspected bacterial meningitis without non-blanching rash, the priority is urgent transfer to hospital (see Management for further information).

Administer parenteral antibiotic treatment only if urgent transfer to hospital is not possible — for example, in remote locations or in adverse weather conditions.

Choice of antibiotic will depend on availability or local policy.

Options include a third generation cephalosporin (preferred), benzylpenicillin (which might be the only parenteral antibiotic available), or chloramphenicol (rarely carried) if there is a clear history of immediate allergic reactions to penicillin or cephalosporins. For further information, see Additional information.

Additional information

Additional information

Choice of pre-hospital antibiotic treatment

Although pre-hospital antibiotic treatment is only indicated if urgent transfer to hospital is not possible, no particular antibiotic is recommended by the National Institute for Health and Care Excellence (NICE) for children and young people with suspected bacterial meningitis without non-blanching rash [National Collaborating Centre for Women's and Children's Health, 2010]. For information regarding the basis for recommending the antibiotics below, see Basis for recommendation.

A third-generation cephalosporin (preferred option — if this is available) such as ceftriaxone (preferred) or cefotaxime.

Ceftriaxone (can be given by slow intravenous injection, deep intramuscular injection, or as a slow intravenous infusion or deep intramuscular injection if a vein is not available [see below]); this is an off-label indication:

For adults — 1000 mg.

CKS identified no guidance which recommends pre-hospital administration of ceftriaxone in children with suspected bacterial meningitis.

Standard therapeutic dosages recommended for children by the manufacturer of ceftriaxone are:

Children 12 years and over — 1000 mg once daily.

Infants and children of up to 12 years — 20 to 50 mg/kg body weight once daily. For children with body weights of 50 kg or more, the usual adult dosage (1000 mg daily) should be used. Doses of 50 mg/kg or over should be given by slow intravenous infusion over at least 30 minutes.

Neonates: a daily dose of 20 to 50 mg/kg body weight (not to exceed 50 mg/kg). The intravenous dose should be given over 60 minutes.

Seek urgent specialist advice if in doubt.

Cefotaxime (ideally intravenously or intramuscularly if a vein is not available [see below]); this is an off-label indication:

For adults and children 12 years of age and older — 1000 mg.

For children younger than 12 years of age — 50 mg/kg.

Benzylpenicillin

This might be the only parenteral antibiotic carried in the GP emergency bag.

Benzylpenicillin should be given ideally intravenously, or intramuscularly if a vein is not available (see below).

For adults and children 10 years of age or older — 1200 mg.

For children 1–9 years of age — 600 mg.

For children younger than 1 year of age — 300 mg.

Benzylpenicillin should be carried in GP emergency bags, and checked regularly to ensure that it is within its expiry date.

Chloramphenicol — rarely carried in GP emergency bags

Chloramphenicol can be considered as an alternative for people with a clear history of immediate allergic reactions to penicillin or cephalosporins (off-label indication)

Route of administration: ideally intravenously or intramuscularly if a vein is not available (see below).

For adults and children 12 years of age and older — 1200 mg.

For children younger than 12 years of age — 25 mg/kg.

Intramuscular injection

If given intramuscularly, the antibiotic should be given as proximally as possible — preferably into a part of the limb that is still warm (as cold areas will be less well perfused).

Basis for recommendation

Basis for recommendation

Choice of antibiotics for people with suspected bacterial meningitis without non-blanching rash

There is a lack of evidence to support the use of pre-hospital antibiotic treatment in people with suspected bacterial meningitis without non-blanching rash.

Although pre-hospital antibiotic treatment is only indicated if urgent transfer to hospital is not possible, no particular antibiotic is recommended by the National Institute for Health and Care Excellence (NICE) [National Collaborating Centre for Women's and Children's Health, 2010]. No high-quality evidence was found on the use of pre-hospital parenteral antibiotics for suspected acute bacterial meningitis (see Basis for recommendation in Management).

For primary care, the choice of antibiotics will be dependent on availability. A third-generation cephalosporin (such as ceftriaxone or cefotaxime) is preferred if this is available. However, these are not commonly carried in GP emergency bags. Consequently, benzylpenicillin may be the only parenteral antibiotic available. Chloramphenicol (if available — rarely carried in GP emergency bags) could be considered if the person has a clear history of penicillin anaphylaxis after a previous dose. These recommendations are extrapolated from the following guidelines and references.

Third generation cephalosporins

The recommendation to offer third generation cephalosporins (in particular, ceftriaxone) is extrapolated from the those issued by NICE, the British Infection Society and the British National Formulary.

In the clinical guideline Bacterial meningitis and meningococcal septicaemia, a third-generation cephalosporin (with ceftriaxone) is recommended by NICE for empirical antibiotic treatment of suspected bacterial meningitis for children older than 3 months of age in secondary care. This is based on the following [National Collaborating Centre for Women's and Children's Health, 2010]:

There is no evidence of a difference in clinical outcomes between third-generation cephalosporins and penicillin- and chloramphenicol-based regimens.

This is based on a Cochrane systematic review (search date: up to March 2007) [Prasad et al, 2007]. However, most of the studies were undertaken in the 1980s and there is uncertainty regarding their methodological quality and/or reporting.

Consequently, the choice of empirical therapy is based on the current antibiotic resistance patterns of the most common organisms causing bacterial meningitis in this age group in England and Wales, and on cost effectiveness. Currently, there is a low prevalence of cefotaxime and ceftriaxone resistance in the UK.

Given the possibility of penicillin resistance among Streptococcus pneumoniae and Haemophilus influenzae, the NICE guideline development group (GDG) considered that a third-generation cephalosporin should be used as empiric therapy in all cases of suspected bacterial meningitis in secondary care. It was also noted that the third-generation cephalosporins sterilized the cerebral spinal fluid (CSF) more quickly than other antibiotics.

NICE reported a four-armed open-label RCT (involving 220 consecutive cases of bacterial meningitis in children 3 months to 15 years of age) which found ceftriaxone sterilized the CSF more rapidly than cefotaxime, ampicillin and chloramphenicol (p < 0.01; results for direct comparison of ceftriaxone and cefotaxime were not reported — although no significant difference in mortality was seen between these two drugs) [Peltola et al, 1989].

Compared to cefotaxime, ceftriaxone has the advantage that it requires only once-daily administration.

Third generation cephalosporins are also recommended by:

Consensus Statement issued by the British Infection Society on the diagnosis, investigation, treatment, and prevention of acute bacterial meningitis in immunocompetent adults (cefotaxime 1 gram or ceftriaxone 1 gram is recommended, see below) [Begg et al, 1999].

The British National Formulary (see below) [BNF 60, 2010].

Benzylpenicillin and chloramphenicol

These two antibiotics are recommended by:

A Consensus Statement issued by the British Infection Society on the diagnosis, investigation, treatment, and prevention of acute bacterial meningitis in immunocompetent adults [Begg et al, 1999].

A single injection of benzylpenicillin is recommended first line. Although the recommendations are based on those for meningococcal disease, they 'feel it reasonable to extend them to all patients with suspected bacterial meningitis'. They acknowledged that no randomized trials on the effects of pre-hospital antibiotic treatment have been performed. They recommended a single injection of benzylpenicillin (1.2 grams) or a cephalosporin (cefotaxime 1 gram or ceftriaxone 1 gram) if penicillin is contraindicated.

The British National Formulary [BNF 60, 2010].

The BNF recommends that 'if a patient with suspected bacterial meningitis without non-blanching rash cannot be transferred urgently to hospital, or if meningococcal disease is suspected, benzylpenicillin can be given before transfer to hospital; cefotaxime may be an alternative in penicillin allergy; chloramphenicol may be used if history of immediate hypersensitivity reaction to penicillin or to cephalosporins' [BNF 60, 2010].

However, no information is given regarding pre-hospital dosage for chloramphenicol or the basis to support this recommendation (see below for BNF dosages).

Route of administration

For benzylpenicillin, cephalosporins and chloramphenicol, the preferred route of administration is by intravenous injection [PHLS Meningococcal Infections Working Party, 1995; ABPI Medicines Compendium, 2009b; Rajapaksa and Starr, 2010]. However, this might be difficult if the person's circulatory system is compromised (for example if they are in shock due to reduced tissue perfusion).

This is also in line with the NICE recommendation on empirical treatment of bacterial meningitis in secondary care [National Collaborating Centre for Women's and Children's Health, 2010].

Although ceftriaxone can be administrated by deep intramuscular injection, slow intravenous injection, or as a slow intravenous infusion [ABPI Medicines Compendium, 2009a], NICE recommends giving intravenous ceftriaxone without delay.

Intramuscular injection is the less preferred as drug absorption can be impaired by shock and hypotension. However, it is recommended if a vein cannot be found [PHLS Meningococcal Infections Working Party, 1995], as this is preferable to giving no antibiotics [Rajapaksa and Starr, 2010].

Pre-hospital antibiotic dosage

For cefotaxime, doses are in line with those recommended by British Infection Society (for adults) [Begg et al, 1999] and the British National Formulary (for children) [BNF for Children, 2010]. This is an off-label use of cefotaxime.

For ceftriaxone, the dose for adults is based on that recommended by the British Infection Society [Begg et al, 1999]. This is an off-label use of ceftriaxone. The 1 gram dose is comparable to the standard therapeutic dosage recommended by the manufacturer of ceftriaxone [ABPI Medicines Compendium, 2009a].

CKS identified no guidance which recommends pre-hospital administration of ceftriaxone in children with suspected bacterial meningitis.

Consequently, only standard therapeutic doses recommended by the manufacturer have been offered. This is in line with the recommended pre-hospital dosage for adults.

For chloramphenicol, the doses are extrapolated from those recommended in a report issued by PHLS for consultants in communicable disease control on the control of meningococcal disease (for people who have a history of penicillin anaphylaxis) [PHLS Meningococcal Infections Working Party, 1995]. This is an off-label use of chloramphenicol.

These dosages are comparable to standard dosages recommended by the manufacturer of chloramphenicol [ABPI Medicines Compendium, 2009b]:

For adults: 1 g of chloramphenicol every 6-8 hours.

For children: 50 mg/kg chloramphenicol daily in divided doses every 6 hours.

Neonates and premature Infants: 25 mg/kg in divided doses.

The BNF does not explicitly recommend any particular dosage for pre-hospital chloramphenicol treatment [BNF 60, 2010]. It offers the following dosages which are compatible to those recommended by PHLS and the manufacturer of chloramphenicol:

By intravenous injection or infusion: 12.5 mg/kg every 6 hours (can be doubled for severe infections such as septicaemia and meningitis, providing high doses reduced as soon as clinically indicated).

For child over 1 month (haemophilus epiglottitis and pyogenic meningitis):12.5–25 mg/kg every 6 hours (high dosages decreased as soon as clinically indicated)

Neonate under 2 weeks: 12.5 mg/kg twice daily

Neonate aged 2 weeks–1 month: 12.5 mg/kg 2–4 times daily.

Safety netting

What safety netting should I consider in a person not requiring admission?

Consider watchful waiting when the person has no specific clinical features of bacterial meningitis, meningococcal disease or meningococcal septicaemia, but it is not possible to exclude the person being in the early stages of the disease.

It is not possible to distinguish between meningococcal disease and other infections (including self-limiting viral infections) in the early stages of infection.

Document all clinical findings

Although it is not possible to entirely exclude a diagnosis of bacterial meningitis or meningococcal septicaemia by checking for clinical features, it is good medical practice to document the absence of these features (see Clinical features in Diagnosis).

Provide symptomatic treatment if appropriate (for example use of antipyretic and self-care advice on managing fever). For further information on managing feverish illness in children, see the CKS topic on Feverish children - management.

Follow up the person within 4–6 hours.

If this is not possible, liaise with another appropriate healthcare professionals regarding arrangement for follow up.

Be aware the infants and young children may only present with non-specific symptoms in the first 4–6 hours. It is rare that meningococcal disease can be excluded within this time.

The early (or prodromal) phase of bacterial meningitis or meningococcal disease can last up to 4 hours in young children, and 8 hours in adolescents. In some cases, this can be much longer.

Consequently, do not exclude the potential diagnosis of meningococcal disease in a young child presenting with non-specific symptoms within the first 4–6 hours of illness.

Provide an appropriate safety net to the individual or parent or carer — even if the assessment does not support a diagnosis of suspected meningitis and/or septicaemia.

This should take into account the person's or parents' anxiety and their capacity to manage the situation, as well as their access to medical assistance (for example proximity to the hospital if they live remotely) — particularly out of hours.

Advise the person to trust their instincts and to seek medical assistance again if their condition worsens, even if the person was seen recently.

Provide appropriate information on warning signs and symptoms of meningitis and septicaemia and when they should seek urgent medical assistance.

Give advice on identification of a non-blanching rash — including the glass test (see Features of meningococcal rash in Diagnosis). Patients and parents or carers using the glass test should be advised to seek urgent medical advice:

If the person is acutely ill and presents with a non-blanching rash. Meningitis and septicaemia should be assumed unless proven otherwise.

If the person becomes acutely ill and their condition has deteriorated, regardless of whether the glass test is positive or negative.

For patient information on how to detect the early stages of possible meningococcal disease (including leaflets), see Self-help information in Scenario: Follow up after discharge.

Basis for recommendation

Basis for recommendation

These recommendations are based on the clinical guideline Management of invasive meningococcal disease in children and young people published by the Scottish Intercollegiate Guidelines Network (SIGN) [SIGN, 2008] and the Meningitis Research Foundation endorsed by the British Medical Association [Meningitis Research Foundation, 2008a]. They have been extrapolated to cover adults.

Follow up and safety net

The serious medical consequences of misdiagnosing meningococcal disease have been highlighted by the National Institute for Health and Care Excellence and the Medical Defence Union [MDU, 2010; NICE, 2010c]. Consequently, it is vital that people with an uncertain diagnosis are followed up and are provided with an appropriate safety net [Almond et al, 2009].

The 'safety net' recommendations are based on guidance issued by SIGN [SIGN, 2008] and by the Meningitis Research Foundation [Meningitis Research Foundation, 2008a].

Glass test

Because of the risk of false-positive and false-negative results, the glass test should not be used as the sole criterion for diagnosing meningococcal septicaemia (for further information, see Features of meningococcal rash in Diagnosis).

Scenario: Managing close contacts

Scenario: Managing close contacts of those with bacterial meningitis and meningococcal septicaemia

0months3060monthsBoth

Overview

Overview

The management of close contacts (involving prophylactic measures) should only be considered after consultation with the local or regional health protection unit.

The management of close contacts for the two main causes of bacterial meningitis are discussed here: meningococcal disease and pneumococcal meningitis.

Seek specialist advice for management of other causes of bacterial meningitis — for example, by Haemophilus influenzae type b (Hib).

For meningococcal disease:

Following confirmation of meningococcal disease in secondary care, the GP and other healthcare professionals may be involved in:

Identifying contacts who are at risk of meningococcal disease.

Reassuring people who may be in contact with the index case but do not require prophylactic treatment.

Prescribing or supplying prophylactic treatments for at-risk groups.

For pneumococcal meningitis:

For close contacts of individual cases of pneumococcal meningitis:

Prophylactic treatment is not indicated as these people are not at increased risk of pneumococcal infection.

Seek specialist advice and liaise closely with the local or regional health protection unit when managing close contacts of clusters or outbreaks in closed settings.

Meningococcal disease

Managing close contacts of meningococcal disease

At-risk groups

Who should be considered for prophylaxis against meningococcal disease?

The decision to offer prophylaxis for close contacts should be made only after discussion with the local or regional health protection unit. The following information is based on guidance issued by the Health Protection Agency.

Be aware that the risk to a contact is low with meningococcal disease. The risk is highest in the first 7 days after a case is diagnosed (see Additional information for definition), and falls sharply thereafter.

Prophylaxis against meningococcal disease should be considered for the following close contacts, regardless of meningococcal vaccination status:

People who have had prolonged close contact with the case in a household-type setting during the 7 days before onset of illness.

For examples: people who are living or sleeping in the same household (including extended household), pupils in the same dormitory, boy/girlfriends, or university students sharing a kitchen in a hall of residence.

People who have had transient close contact with a case only if they have been directly exposed to large particle droplets/secretions from the respiratory tract of a case around the time of admission to hospital (for further information, see Prophylaxis in healthcare settings).

Chemoprophylaxis should be taken by the case when they are able to take oral medication and before hospital discharge (unless the disease has already been treated with ceftriaxone).

Chemoprophylaxis is still required for people treated with cefotaxime as it is unknown if this antibiotic eradicates carriage.

Seek specialist advice and liaise closely with the local or regional health protection unit:

When there is uncertainty regarding whether prophylaxis should be given or not (for example if a case occurs in a group of children looked after by the same childminder or among a circle of close friends).

In dispersal settings where close contacts have been identified and where contact has now finished (for example people sleeping in the same room on holiday or at university). Attempts should be made to arrange prophylactic treatment within 1 week of dispersal if practicable.

For information on who should not be offered prophylaxis, see Prophylaxis not indicated.

Additional information

Additional information

Definition of 'case'

A confirmed case (that requires public health action) is defined by the Health Protection Agency (HPA) as a clinical diagnosis of meningitis, septicaemia or other invasive disease (e.g. orbital cellulitis, septic arthritis) with at least one of the following [HPA, 2011]:

Neisseria meningitidis isolated from normally sterile site.

Gram negative diplococci in normally sterile site.

Meningococcal DNA in normally sterile site.

Meningococcal antigen in blood, cerebral spinal fluid or urine.

Although not meeting the definition of a confirmed case, the HPA highlights that meningococcal infection of the conjunctiva is considered to be an indication for public health action because of the high immediate risk of invasive disease [HPA, 2011].

Basis for recommendation

Basis for recommendation

These recommendations are taken from Guidance for public health management of meningococcal disease in the UK, published by the Health Protection Agency (HPA) [HPA, 2011].

Risk to household contacts

The HPA highlights that the risk of meningococcal disease for close contacts is low [HPA, 2011]. Around 97% cases of meningococcal disease are sporadic.

For people living in the same household as the index case, the risk is highest in the first 7 days after the case is diagnosed and subsequently falls rapidly. A household is defined by HPA (in line with Office for National Statistics definition) as 'one person living alone or a group of people who share common housekeeping or a living room' [HPA, 2011].

If prophylaxis is not given, the absolute risk is around 1 in 300 during the period 1–30 days after an index case. After 4 weeks, the risk is probably close to background level.

This increased risk may be due to a number of factors, such as genetic susceptibility in the family, increased exposure to virulent meningococci, and environmental factors.

Risk to non-household contacts

The risk for contacts outside the household is even lower — presumably related to the lower intensity of exposure ot the virulent strains [HPA, 2011].

Data from England and Wales (1995–2001) indicate that after a case of meningococcal disease in pre-school or primary or secondary school, the absolute risk to children at the same institution within the next 4 weeks is [Davison et al, 2004]:

Pre-school group — around 1 in 1500.

Primary school — around 1 in 18,000.

Secondary school — around 1 in 33,000.

Reports of clusters in other settings (for example the workplace) are rare.

Risk to healthcare professionals

For healthcare professionals in contact with cases of meningococcal disease, the risk is very low [Pollard and Begg, 1999; HPA, 2011]

There is a relatively increased risk of disease in the first 10 days after exposure. One study estimated an attack rate of 0.8 per 100,000 at-risk healthcare workers [Gilmore et al, 2000]. For further information, see Prophylaxis in healthcare settings.

Prophylaxis not indicated

When is prophylaxis not indicated for contacts of meningococcal disease?

The decision to offer prophylaxis should only be made after consultation with the local or regional health protection unit. The following information is based on guidance issued by the Health Protection Agency.

Prophylaxis against meningococcal disease is not indicated for the following contacts (unless they are already classed as close contacts — see At-risk groups):

Staff and children attending same nursery or crèche.

Students/pupils in same school, class, or tutor group.

Work or school colleagues.

Friends.

Residents of nursing or residential homes.

People who kiss on the cheek or mouth (intimate kissing would normally bring the contact into the 'close prolonged contact' category).

People sharing food or drink, or other activities with a similar low level of salivary contact.

People attending the same social function.

People travelling in the next seat in the same plane, train, bus, or car.

Prophylaxis is also not indicated for post-mortem contact with a case:

Kissing the body is not considered to be risk. Body bags are not necessary.

Transportation to other countries for burial or cremation does not pose a risk.

There is no restriction on embalming.

Basis for recommendation

Basis for recommendation

These recommendations are on Guidance for public health management of meningococcal disease in the UK published by the Health Protection Agency (HPA) [HPA, 2011]. They are based on expert opinion.

Transient contact

For transient contact with the index case before acute illness, this is regarded as unlikely to be an important risk factor for disease.

Consequently, prophylaxis is not indicated for people with mere proximity to the case (for example during travel in a plane, bus, or car).

Although a US guideline considered offering prophylaxis to people seated next to an index case for more than 8 hours [MMWR, 2001], the HPA highlighted that a recent review by the European Centre for Disease Prevention and Control only identified one possible transmission — during an 11-hour flight in which two passengers contracted serogroup B meningococcal disease (onset of symptoms two and five days after landing, respectively) [ECDC, 2009].

Low-level salivary contact

Low-level salivary contact (such as sharing cups or glasses) was not considered a risk factor. This was based on a US study (involving 258 students), which found a very low isolation rate for Neisseria meningitidis in saliva swabs (0.4%), compared with 32.2% and 19.4% for swabs taken from the nasopharynx and tonsils, respectively [Orr et al, 2003].

Pre-school and primary and secondary schools

The risk of contacts for pupils in a pre-school group or primary or secondary school is low — considerably lower than that for household contacts (see Basis for recommendation for At-risk groups).

The HPA identified one retrospective study in European countries, which supported a policy of giving chemoprophylaxis to the whole nursery instead of treating only close contacts. However, after taking into account heterogeneity in the data, there was no significant difference between the policies [Boccia et al, 2006].

Having considered the estimates of risk and the benefit of treatment, the HPA recommended that the UK policy of not giving antibiotics to pre-school groups after a single case should be maintained, as the benefit of antibiotic prophylaxis in this setting is unknown. In addition:

The potential for risk reduction with antibiotic prophylaxis is reduced owing to the time delay from identification of the case to antibiotic administration within the institute.

Harm may arise from adverse drug reactions and eradication of naturally immunising strains from the naopharynx (see below).

Such an antibiotic policy may lead to antibiotic resistance.

The HPA also highlights that, as one goes further outside the case household:

The lower the chance of finding a carrier of a pathogenic meningococcal strain.

The greater the chance that treatment will do harm by eradicating carriage of non-pathogenic organisms that may generate cross-protective immunity. This particularly applies in young children who are more likely to be carrying Neisseria lactamica than Neisseria meningitidis.

Other settings outside the household

The HPA only identified rare reports of clusters in settings outside the household (such as the work place). The level of risk was also considered to be much lower than that for educational settings [HPA, 2011].

Prophylactic treatments

What prophylactic treatments are offered to close contacts of meningococcal disease?

Prophylactic treatment of close contacts should only be considered after consultation with the local or regional health protection unit. The following information is based on guidance issued by the Health Protection Agency.

For close contacts who are at risk of meningococcal disease (see At-risk groups):

Offer the following prophylactic measures as soon as possible (ideally within 24 hours) after the diagnosis of the index case:

Chemoprophylaxis (regardless of immunization status)— the following antibiotics are recommended:

Ciprofloxacin (single-dose oral treatment, off-label use) — drug of choice and is recommended for use in all age groups and pregnancy.

Rifampicin (2 days of oral treatment) — licensed and recommended for all age groups.

Azithromycin (single-dose oral treatment, off-label use) — an alternative antibiotic for chemoprophylaxis in pregnant women.

Ceftriaxone (single-dose injection, off-label use) — use for certain patient groups (for example pregnant women).

Remind the person that the treatment is not fully protective and close contacts must be alert to the symptoms and signs of meningococcal disease.

For further information (including dosage), see the sections on Ciprofloxacin, Rifampicin, and Chemoprophylaxis for pregnant or breastfeeding women under Prescribing information.

Vaccination (if not previously immunized) — depending on the infective strain of Neisseria meningitidis isolated. Vaccines are available against serogroups A, C, W135, and Y. For further information, see Vaccination recommendations.

Chemoprophylaxis should be given first and the decision to offer vaccination should be made when the results of serogrouping are available.

If there is a delayed report of a case, chemoprophylaxis (and vaccination if appropriate) should be offered up to 4 weeks after onset of illness.

For cases in contacts who have received prophylaxis

If further cases occur within a group of close contacts in the 4 weeks after chemoprophylaxis, repeat prophylaxis with an alternative antibiotic.

For index case

Prophylaxis will be given to the index case before hospital discharge unless the disease has already been treated with ceftriaxone. Those treated with cefotaxime should still receive prophylaxis because it is not known whether cefotaxime eradicates carriage.

Vaccination recommendations

Vaccination recommendations

The following recommendations on vaccination of close contacts and index cases are based on guidance issued by the Health Protection Agency [HPA, 2011] and the Department of Health [DH, 2011]. It should be noted that [DH, 2011]:

Chemoprophylaxis should be given as soon as possible, while the decision to offer vaccination should be made when the results of serogrouping are available.

Current vaccines do not protect against serogroup B meningococcal infection.

Close contacts — confirmed serogroup C infection

Vaccination with a meningococcal C conjugate vaccine should be offered to all close contacts who have not been previously immunized with this vaccine.

Close contacts who are partially immunized should complete a course of meningococcal C vaccination.

Close contacts of any age who were only immunized in infancy and those who completed the recommended immunization course (including the 12-month booster) more than one year before should be offered an extra dose of MenC conjugate vaccine.

Close contacts — confirmed serogroup A, W135, or Y infection

Vaccination with a quadrivalent conjugate vaccine (Menveo®) should be offered to all close contacts of any age

Those younger than 12 months of age will require a second dose 1 month after the first.

Vaccination of index case

Offer meningococcal C conjugate vaccine (according to the recommended national schedule) to any unimmunized index cases under the age of 25 years (whatever the serogroup).

For further information, see the CKS topic on Immunizations - childhood.

For confirmed cases of serogroup C disease who have previously been immunised with meningococcal C conjugate (or polysaccharide) vaccine:

Offer a booster dose of the vaccine around the time of discharge from hospital.

For index cases who are in the risk-group for meningococcal disease (for example asplenia, complement deficiency) and have not been immunized (or are incompletely immunized for age) with the quadrivalent MenACWY conjugate vaccine:

Complete the recommended immunization course (two doses 1 month apart if aged less than 1 year; one dose after first birthday),

Offer an extra dose of the quadrivalent MenACWY conjugate vaccine if they have received this vaccine more than 12 months previously.

Basis for recommendation

Basis for recommendation

These recommendations are based on Guidance for public health management of meningococcal disease in the UK published by the Health Protection Agency (HPA) [HPA, 2011] and information from the Department of Health's: Immunization against infectious disease — the Green Book [DH, 2011].

Chemoprophylaxis

Antibiotic prophylaxis is given to reduce the risk of invasive disease by eradicating carriage in the following close contacts [HPA, 2011]:

Established carriers who pose an infection risk to other people.

Those who may have newly acquired the invasive strain and who may themselves be at risk.

One systematic review (search date: up to 2003) identified limited evidence from a meta-analysis of four observational studies and one small trial. It found that chemoprophylaxis given to household contacts reduced the risk of meningococcal disease in the 1–30 days after onset of disease in the index patient (risk ratio 0.11, 95% CI 0.02 to 0.58). This means that the number of people who need to be treated to prevent one case of meningitis infection occurring was about 218 (95% CI 121 to 1135) [Purcell et al, 2004].

Vaccination

Vaccination is offered to reduce the long-term risk of disease in close contacts (if previously not immunized).

It is estimated that, for un-immunized close contacts, the number needed to vaccinate with the meningococcal C vaccine to prevent one case of confirmed serogroup C infection is around 1000 [HPA, 2011].

This is based on a systematic review (five studies and one unpublished report, 4630 primary cases and 30 household clusters with 40 subsequent cases)which examined the effectiveness of vaccination (in addition to chemoprophylaxis) in preventing meningococcal disease among household contacts [Hoek et al, 2008].

Vaccination is not recommended by the HPA for people who received chemoprophylaxis for transient contact and in dispersal settings.

Prophylaxis for the index case after benzylpenicillin treatment

It has been found that around 5% of people treated with benzylpenicillin continued to carry the invasive strain even after completing treatment and before hospital discharge [HPA, 2011].

Consequently, prophylaxis is recommended to eradicate carriage to reduce the risk that convalescent cases may pose to other household contacts after hospital discharge [HPA, 2011].

Prophylaxis in healthcare settings

When and what prophylactic treatments should be offered in healthcare settings for close contacts of meningococcal disease?

The management of close contacts in healthcare settings should only be considered after consultation with the local or regional health protection unit. The following information has been reproduced from guidance issued by the Health Protection Agency.

Healthcare workers should reduce the possibility of exposure to large particle droplets (for example by wearing surgical masks, using closed suction) especially when carrying out airway management procedures, so that chemoprophylaxis is not needed.

For healthcare workers who are in contact with cases of meningococcal disease, there is an increased relative risk of the disease in the 10-day period after exposure. However, the absolute risk is very low.

Chemoprophylaxis is indicated for people whose mouth or nose is directly exposed to large particle droplets/secretions from the respiratory tract of a probable or confirmed case of meningococcal disease during acute illness until completed 24 hours of systemic antibiotics.

This type of exposure will only occur among staff who are working close to the face of the case without wearing a mask or other mechanical protection.

This can occur when using suction during airway management, inserting an airway, intubating, or if the patient coughs directly into the face of the healthcare worker.

Recommended chemoprophylaxis regimens:

Ciprofloxacin 500 mg as a single dose or rifampicin 600 mg orally twice daily for 2 days.

Chemoprophylaxis is not indicated for:

People who are providing general medical or nursing care of cases.

Exposure of the eyes to respiratory droplets. However, because such exposure carries a low risk of meningococcal conjunctivitis and subsequent invasive disease, advise the person to seek early treatment if conjunctivitis develops within 10 days of exposure.

Routine vaccination of healthcare workers with meningococcal conjugate vaccines is not recommended.

Seek specialist advice for healthcare workers (including dentists) and contacts of cases on a hospital ward where the diagnosis of meningococcal disease is initially unsuspected and not treated with systemic antibiotics.

Chemoprophylaxis is usually not indicated for patients or staff contacts of such cases as a hospital ward is not equivalent to a household setting.

However, the threshold for giving chemoprophylaxis should be lower for immunocompromised contacts who may be at increased risk of invasive disease.

Consequently, risk assessment is advised.

Basis for recommendation

Basis for recommendation

These recommendations are on Guidance for public health management of meningococcal disease in the UK published by the Health Protection Agency (HPA) [HPA, 2011]. They are in line with an earlier recommendations issued by the working group of the Public Health Laboratory Service (PHLS) Meningococcus Forum [Stuart et al, 2001].

Risk to healthcare workers

For healthcare workers who are in contact with cases of meningococcal disease, there is an increased relative risk of the disease in the 10-day period after exposure. However, the absolute risk is very low [HPA, 2011].

In a retrospective survey to measure the risk of meningococcal disease in health-care workers who had been in close contact with cases in England and Wales, only three pairs of primary and health-care-worker cases were identified between 1982 and 1996 [Gilmore et al, 2000]. From this, the study estimated an attack rate in health-care workers of 0·8 per 100 000 health-care workers at risk, which is 25 times that in the general population (p = 0·0003). The authors concluded that the excess risk is small and inappropriate use of prophylactic antibiotics should be avoided.

The data were consistent with a higher (but unquantifiable) risk in those more heavily exposed to nasopharyngeal secretions of cases around the time of admission to hospital.

In addition, meningococcal carriage rate decrease rapidly in the patient after the initiation of intravenous benzylpenicillin [HPA, 2011].

Meningococci are undetectable by nasopharyngeal swabbing after 24 hours on benzylpenicillin treatment.

A similar or more rapid effect on suppression of carriage is expected with third generation cephalosporins (such as ceftriaxone). Both ceftriaxone and rifampicin are known to be effective in eradicating carriage, whereas penicillin is thought to suppress but not eradicate carriage.

Meningococcal conjugate vaccines

The HPA do not recommend routine vaccination of healthcare workers with meningococcal conjugate vaccines because [HPA, 2011]:

The serogroup of the infecting strain is not usually known. Consequently previous vaccination would not obviate the need for chemophylaxis.

Most cases are caused by serogroups other than A, C, Y and W135 and would not be prevented by the quadrivalent conjugate vaccine.

Pneumococcal meningitis

How should I manage close contacts of pneumococcal meningitis?

The management of close contacts should only be considered after consultation with the local or regional health protection unit. The following information is based on guidance issued by the Department of Health and the Health Protection Agency.

For close contacts of individual case of pneumococcal meningitis (or other invasive pneumococcal disease), inform the person that:

They are not at increased risk of pneumococcal infection.

Antibiotic prophylaxis and immunization is not indicated.

Seek specialist advice and liaise closely with the local or regional health protection unit when managing close contacts of clusters or outbreaks in closed settings.

Further information can be found in the Interim UK guidelines for the public health management of clusters of serious pneumococcal disease in closed settings issued by the Health Protection Agency (available at www.hpa.org.uk).

Basis for recommendation

Basis for recommendation

These recommendations are based on Interim UK guidelines for the public health management of clusters of serious pneumococcal disease in closed settings issued by the Health Protection Agency [HPA, 2008] and the handbook Immunisation against infectious disease ('The Green Book') issued by the Department of Health [DH, 2006].

Scenario: Follow up after discharge

Scenario: Follow up after hospital discharge for bacterial meningitis and meningococcal septicaemia

0months3060monthsBoth

Overview

Overview

For people with confirmed bacterial meningitis, meningococcal disease or meningococcal septicaemia, the GP and other primary care healthcare professionals may be involved in follow up after the person has been discharged from hospital:

To provide information and support (for example on driving and on support groups).

To check with the person or parents that the appropriate hospital follow up has been arranged (for example a hearing test).

To continue to monitor for any long term complications of bacterial meningitis and/or meningococcal septicaemia.

Support and follow up

What support and follow up are recommended in primary care after hospital discharge?

People discharged from hospital who are recovering from bacterial meningitis, meningococcal disease or meningococcal septicaemia

Provide information and support for the person and their family (if this is not done on discharge) — particularly if the person experiences permanent disability or has died.

For information on support groups, see Self-help information.

Give or reinforce advice on driving if appropriate. For further information, see Information on driving.

Check with the person or parents whether appropriate hospital follow up has been arranged.

Before hospital discharge, the person should be assessed for the following:

Any potential sensory, neurological, psychosocial, orthopaedic, cutaneous, or renal morbidities.

Any potential long-term effects of their condition and pattern of recovery (see Complications in Background information).

The person should be referred to the appropriate specialists after discharge if required.

For children and young people, this includes a formal audiological assessment which should be performed as soon as possible, preferably before discharge or within 4 weeks of being fit to test.

For adults, a follow up with audiometry is mandatory if the person has symptoms or signs of deafness on discharge.

Be alert for possible late-onset sensory, neurological, orthopaedic, and psychosocial effects of bacterial meningitis and meningococcal septicaemia.

For adults who have an uncomplicated recovery and are asymptomatic:

They may experience headache and fatigue for some time after the acute illness.

Offer reassurance that this is common and they will recover without any complications.

Basis for recommendation

Basis for recommendation

These recommendations are based on the clinical guideline Bacterial meningitis and meningococcal septicaemia published by the National Institute for Health and Care Excellence (NICE) [NICE, 2010c], the clinical guideline Management of invasive meningococcal disease in children and young people published by the Scottish Intercollegiate Guidelines Network (SIGN) [SIGN, 2008], and a Consensus Statement on Diagnosis, Investigation, Treatment and Prevention of Acute Bacterial Meningitis in Immunocompetent Adults published by the British Infection Society [Begg et al, 1999].

Information on driving

What are the issues regarding driving in adults after recovering from meningitis?

Adults recovering from meningitis should be made aware of the legal issues regarding driving. These apply to:

Car drivers and motorcycles — Group 1 entitlement.

Drivers of large goods vehicles (LGVs) and passenger carrying vehicles (PCVs, such as minibuses) — Group 2 entitlement.

Document the advice provided in the person's medical records.

If the person experienced no seizures during acute illness phase and convalescence

All drivers and motorcyclists: They may resume driving provided there is no residual disabling symptoms and clinical recovery is complete.

Notify the Driver and Vehicle Licensing Agency (DVLA) only if there is residual disability.

If the person experienced seizures during the acute febrile illness phase

For car drivers and motorcyclists:

Do not drive for 6 months from the date of the last seizure(s).

The driving licence is refused or revoked for 6 months from the date of the last seizure. However, the licence will remain valid until 70 years of age.

For LGV and PCV drivers:

They must stop driving and notify the DVLA.

They can resume driving if they have no seizures for 5 years and are not taking any anticonvulsant medications during this time.

If the person experienced seizures during or after convalescence

All drivers and motorcyclists must stop driving and notify the DVLA. The epilepsy regulations will apply.

For up-to-date information on legal issues (including the epilepsy regulations), consult the At a glance document which is available from the DVLA (www.gov.uk).

Patient information on surrendering the driving licence to the DVLA (including appropriate forms) can be found on the www.gov.uk website (www.gov.uk).

Basis for recommendation

Basis for recommendation

These recommendations are based on guidelines issued by the Driver and Vehicle Licensing Agency [DVLA, 2010].

Self-help information

Where can I find self-help information on meningitis and meningococcal septicaemia?

Information on meningitis should be given to parents and carers at the time of initial presentation and after diagnosis. This should cover the short- and long-term effects of the disease and include contact details of patient support organizations.

Self-help information on recognizing the signs of meningitis and septicaemia is available from:

NHS Choices (www.nhs.uk) includes a:

Health tool, Meningitis symptom alert, to help to recognize the signs of meningitis in babies; produced in conjunction with The Meningitis Trust.

Patient information leaflets on the symptoms and signs of meningitis.

Meningitis Research Foundation (www.meningitis.org).

Free 24-hour helpline for the UK: 0808 800 3344.

The Meningitis Trust (http://www.meningitis-trust.org).

Offers free services, providing emotional, practical, and financial support for people who have been affected by meningitis.

Free 24-hour helpline for UK: 0808 801 0388.

Brain and Spine Foundation (www.brainandspine.org.uk).

Free phone number: 0808 808 1000.

Meningitis

The National Deaf Children's Society (NDCS) (www.ndcs.org.uk).

Free phone number: 0808 800 8880 (Monday to Friday: 9.30 am to 5 pm and Saturday: 9.30 am to midday).

Meningitis and childhood deafness (pdf) .

Basis for recommendation

Basis for recommendation

The recommendation to offer information at the time of initial presentation and after diagnosis is in line with guidance issued by the National Institute for Health and Clinical Excellence [National Collaborating Centre for Women's and Children's Health, 2010].

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://medicines.org.uk/emc), or the British National Formulary (BNF) (www.bnf.org).

Chemoprophylaxis

Chemoprophylaxis against meningococcal disease

Ciprofloxacin

Ciprofloxacin for chemoprophylaxis of meningococcal disease

Prescribing issues

What are the prescribing issues for ciprofloxacin for chemoprophylaxis of meningococcal disease?

Prophylactic antibiotics should only be prescribed after consultation with the local or regional health protection unit. Check local policy. The following general information is based on the guidance (pdf) issued by the Health Protection Agency (HPA, available on www.hpa.org.uk) and is intended only as a guide. For further information, consult the HPA guidance and the manufacturers' Summaries of Product Characteristics (available on www.medicines.org.uk).

Ciprofloxacin is recommended for chemoprophylaxis of meningococcal disease (off-label indication) in all age groups as well as for women who are pregnant or breastfeeding (see Chemoprophylaxis for pregnant or breastfeeding women for further information).

Ciprofloxacin is preferred over rifampicin (no longer drug of choice) because of the following advantages over rifampicin:

Treatment only requires a single dose (see below).

Ciprofloxacin is not a potent enzyme inducer and does not affect hormonal contraceptives (see below).

It is more readily available in community pharmacies.

Dosage of ciprofloxacin:

Adults and children older than 12 years of age: a single dose of 500 mg.

Children 5–12 years of age: a single dose of 250 mg.

Children 2–4 years of age: a single dose of 125 mg.

Drug interactions

A single dose of ciprofloxacin is unlikely to have a significant effect.

Although ciprofloxacin can have an unpredictable effect on epilepsy, it may be preferable to rifampicin if the person is taking phenytoin.

Adverse effects

These may include nausea, diarrhoea, rash, fatigue or facial swelling, and tendon damage.

Advise the person to seek urgent medical attention if they experience breathing difficulties (rare adverse effect) after taking ciprofloxacin.

Basis for recommendation

These recommendations are based on guidance issued by the Health Protection Agency (HPA) on the public health management of meningococcal disease in the UK [HPA, 2011].

Use in children and growing adolescents

Due to joint/cartilage damage seen in immature animals given ciprofloxacin, the manufacturers do not recommend the use of ciprofloxacin in children or growing adolescents unless benefits of treatment are considered to outweigh risks.

For chemoprophylaxis of meningococcal disease in children, the HPA recommend this off-label use because it found evidence of lack of joint damage in young children given ciprofloxacin [HPA, 2011].

In the studies identified, the HPA found the risk of arthropathy due to ciprofloxacin to be very low. Arthralgia were transient and most were coincidental. Adverse effects resolved after treatment cessation in all the studies.

One randomized controlled trial (undertaken in Malawi) on eradicating meningococcal nasal carriage eradication found no difference in the rate of adverse effects between ciprofloxacin and rifampicin in contacts of persons with meningococcal meningitis [Cuevas et al, 1995]. In the ciprofloxacin group, 469 contacts were between 2 to 18 years of age (ciprofloxacin dose: 15 mg/kg as a single dose). Only 6 children reported adverse effects with only mild abdominal pain considered to be related to ciprofloxacin therapy.

A review of multiple controlled prospective and retrospective studies (using higher doses of ciprofloxacin) found the rate of adverse events in children given ciprofloxacin was similar to those on other antibiotics [Drew et al, 1976; Burkhardt et al, 1997]. No long-term cartilage damage was found.

Similar clinical growth was seen in a controlled study when 111 neonates receiving ciprofloxacin were compared to 100 controls, even at one year of follow-up [Drossou-Agakidou et al, 2004].

The risk of tendon disorders was similar low (0.8%) in a large retrospective study involving 4.531 children who were given ciprofloxacin or azithromycin [Yee et al, 2002].

Advice

What advice should be given to someone prescribed ciprofloxacin for chemoprophylaxis of meningococcal disease?

Provide verbal and written information on ciprofloxacin and meningococcal disease.

For further information, see Self-help information in Scenario: Follow up after discharge and the guidance (pdf) issued by the Health Protection Agency (www.hpa.org.uk), which includes sample patient information leaflets on chemoprophylaxis.

Remind the person that the treatment is not fully protective and close contacts must be alert to the symptoms and signs of meningococcal disease.

Advise the following:

Ciprofloxacin should taken swallowed whole with an adequate amount of liquid. Drink plenty of fluids for rest of the day to avoid excessive alkalinity of urine.

Do not take ciprofloxacin with dairy products (such as milk or yoghurt) or with mineral-fortified drinks alone (such as calcium-fortified orange juice).

Adverse effects of ciprofloxacin include:

Nausea, diarrhoea, rash, fatigue or facial swelling, and tendon damage.

Breathing difficulties (rare) — tell the person to seek urgent medical attention if they experience this after taking ciprofloxacin.

Basis for recommendation

These recommendations are based on guidance issued by the Health Protection Agency (HPA) on the public health management of meningococcal disease in the UK [HPA, 2011].

Rifampicin

Rifampicin for chemoprophylaxis of meningococcal disease

Prescribing issues

What are the prescribing issues for rifampicin for the chemoprophylaxis of meningococcal disease?

Prophylactic antibiotics should only be prescribed after consultation with the local or regional health protection unit. Check local policy. The following general information is based on the guidance (pdf) issued by the Health Protection Agency (HPA, available on www.hpa.org.uk) and is intended only as a guide. For further information, consult the HPA guidance and the manufacturers' Summaries of Product Characteristics (available on www.medicines.org.uk).

For the chemoprophylaxis of meningococcal disease, rifampicin is licensed for use in all age groups (see below for dosage). However, compared to ciprofloxacin, it is no longer drug of choice for meningococcal chemoprophylaxis because:

It is associated with rapid induction of resistance.

It inhibits contraceptives.

It has a longer regime duration.

It is usually only available from hospital pharmacies.

Rifampicin is also no longer recommended for use in pregnant women (see Chemoprophylaxis for pregnant or breastfeeding women).

Rifampicin is contraindicated in the presence of jaundice or if the person is currently being treated with a combination of saquinavir and ritonavir (owing to the potential increased risk of hepatotoxicity).

Be aware that rifampicin is a potent inducer of certain cytochrome P450 enzymes. Consequently, it can interact with a number of drugs, including hormonal contraceptives (see Advice), anticoagulants, and phenytoin.

The drug is available in the following formulations: rifampicin 150 mg capsules, 300 mg capsules, and 100 mg/5 mL oral suspension.

Licensed dosages for chemoprophylaxis of meningococcal disease

Rifampicin should be taken twice daily for 2 days.

Adults and children older than 12 years of age: 600 mg twice daily for 2 days.

Children 1–12 years of age: 10 mg/kg twice daily for 2 days.

Infants younger than 12 months of age: 5 mg/kg twice daily for 2 days.

Suitable doses for children based on average weight for age

0–2 months: 20 mg (l mL of 100 mg/5 mL oral suspension) twice daily for 2 days (off-label indication).

3–11 months: 40 mg (2 mL of 100 mg/5 mL oral suspension) twice daily for 2 days.

1–2 years: 100 mg (5 mL of 100 mg/5 mL oral suspension) twice daily for 2 days.

3–4 years: 150 mg (7.5 mL of 100 mg/5 mL oral suspension) twice daily for 2 days.

5–6 years: 200 mg (10 mL of 100 mg/5 mL oral suspension) twice daily for 2 days.

7–12 years: 300 mg (can be given as a capsule or 15 mL of 100 mg/5 mL oral suspension) twice daily for 2 days.

The drug should be taken at least 30 minutes before a meal or 2 hours after a meal.

Adverse effects of rifampicin include:

Nausea, diarrhoea, urticaria and rash, fatigue, headache, and drowsiness.

Orange/reddish staining of urine, sputum, and tears — which may stain soft contact lenses (see Advice) and nappies.

Basis for recommendation

These recommendations are based on guidance issued by the Health Protection Agency (HPA) on the public health management of meningococcal disease in the UK [HPA, 2011].

Advice

What advice should be given to someone prescribed rifampicin for chemoprophylaxis of meningococcal disease?

Emphasize the importance of completing the 2-day course of treatment.

Provide verbal and written information on rifampicin and meningococcal disease.

For further information, see Self-help information in Scenario: Follow up after discharge and the guidance (pdf) issued by the Health Protection Agency (www.hpa.org.uk), which includes sample patient information leaflets on chemoprophylaxis.

Remind the person that the treatment is not fully protective and close contacts must be alert to the symptoms and signs of meningococcal disease.

Warn that adverse effects of rifampicin include:

Nausea, diarrhoea, urticaria and rash, fatigue, headache, and drowsiness.

Orange/reddish staining of urine, sputum, and tears — which may stain soft contact lenses (see below) and nappies.

For people using soft contact lenses:

Warn that rifampicin may permanently stain soft contact lenses.

Consequently, they should not be worn for 1 week following completion of rifampicin treatment.

For women taking combined hormonal contraceptives (pills, patches, and vaginal rings) or progestogen-only pills (POPs):

Warn that rifampicin will reduce the efficacy of these methods of contraception.

For information on managing women taking combined hormonal contraceptives or progestogen-only pills, see the CKS topics on Contraception - combined hormonal methods and Contraception - progestogen-only methods.

Basis for recommendation

These recommendations are based on guidance issued by the Health Protection Agency on the public health management of meningococcal disease in the UK [HPA, 2011].

Chemoprophylaxis for pregnant or breastfeeding women

Which chemoprophylaxis regimen against meningococcal disease is recommended for women who are pregnant or breastfeeding?

Prophylactic antibiotics should only be prescribed after consultation with the local or regional health protection unit. Check local policy. The following general information is based on the guidance (pdf) issued by the Health Protection Agency (HPA, available on www.hpa.org.uk) and is intended only as a guide. For further information, consult the HPA guidance and the manufacturers' Summaries of Product Characteristics (available on www.medicines.org.uk).

For pregnant women:

Choice of antibiotics are ciprofloxacin, ceftriaxone or azithromycin.

Rifampicin is no longer recommended for use in pregnancy.

Ciprofloxacin (given as a single dose of 500 mg, off-label use) has the advantage that it is easily accessible in primary care.

Azithromycin (also given as a single dose of 500 mg, off-label use) can also be used for chemoprophylaxis.

Ceftriaxone is is restricted to certain patient groups as it has to be given by injection and the injection is painful.

For breastfeeding women:

Options are:

Ciprofloxacin — given as a single dose of 500 mg, off-label use.

Rifampicin — 600 mg twice daily for 2 days.

Basis for recommendation

These recommendations are based on guidance produced by the Health Protection Agency (HPA) on the management of meningococcal disease in UK [HPA, 2011]. The safety of different antibiotic regimens used for chemoprophylaxis of meningococcal disease in pregnant and breastfeeding women is poorly studied.

Only one trial (undertaken in Malawi) was identified by the HPA [Cuevas et al, 1995]. Ceftriaxone was given as a single intramuscular injection (2 g) to 176 pregnant and lactating women (to eradicate meningococcal nasal carriage) who have been in contact with people with microbiologically confirmed meningococcal meningitis. Only five women reported mild adverse effects (nausea, diarrhoea or abdominal pain). However, there was no control group in this stud

Chemoprophylaxis for pregnant women

Ciprofloxacin

Although unlicensed and not recommended by the manufacturer for use in pregnancy, HPA concluded that short duration of ciprofloxacin treatment for other indications (such as inflammatory bowel disease) appears to be safe [HPA, 2011].

When used in the first trimester of pregnancy, fluoroquinolones have not been associated with an increased risk of major malformations or other adverse effects on pregnancy outcomes (data mainly available for ciprofloxacin and norfloxacin) [Schaefer et al, 2007]. Fluoroquinolones have not been found to be teratogenic in animals [Schaefer et al, 2007].

Azithromycin

Although recommended by HPA for the chemoprophylaxis of meningococcal disease, no information is given to support the use of azithromycin (off-label use) [HPA, 2011].

Although shown to pass the placenta in reproduction toxicity studies, no teratogenic effects have been observed for azithromycin. Given its safety has not been confirmed in pregnancy, the manufacturer recommends that it 'should only be used during pregnancy if definitely indicated' [ABPI Medicines Compendium, 2011].

Ceftriaxone

There is limited evidence from a small trial supporting its use during pregnancy (see above) [Cuevas et al, 1995]. Given it has to be given by painful intramuscular injection, HPA does not recommended it first line.

Rifampicin

Although recommended in the previous edition of the guidance [HPA, 2006], rifampicin is no longer recommended by the HPA for use in pregnancy [HPA, 2011]. Although rifampicin teratogenicity has been found in high doses in animals, evidence from epidemiological studies have not shown any notable risk in humans when used for tuberculosis treatment.

Chemoprophylaxis during breastfeeding

Only ciprofloxacin and rifampicin are recommended by HPA [HPA, 2011]. This is based on a systematic review of antibiotic use in lactation which found these antibiotics to be compatible with breastfeeding [Nahum et al, 2006]. Other antibiotics used for chemoprophylaxis of meningococcal disease were not studied.

Evidence

Evidence

Supporting evidence

This section summarizes the evidence that supports the use of pre-admission antibiotic treatment for people with suspected bacterial meningitis or meningococcal septicaemia in primary care.

Pre-admission antibiotic administration

Evidence on pre-admission antibiotic administration for people with suspected bacterial meningitis or meningococcal disease

There is an absence of evidence from controlled trials to show that pre-hospital treatment with antibiotics reduces mortality and morbidity in people with suspected meningococcal disease. However, antibiotics are unequivocally recommended by national guideline groups on the basis of their likely benefits and lack of harm.

No evidence was identified in people with suspected bacterial meningitis.

Bacterial meningitis

CKS found no studies examining the use of pre-hospital antibiotic treatment in people with suspected bacterial meningitis. This is in line with the following guidelines:

The National Institute for Health and Care Excellence (NICE) identified no high-quality evidence on the effects of pre-hospital antibiotics in children and young people with suspected bacterial meningitis [National Collaborating Centre for Women's and Children's Health, 2010].

This is also highlighted by the guidelines issued by The European Federation of Neurological Societies (EFNS) on the management of community-acquired bacterial meningitis in older children and adults [Chaudhuri et al, 2008] and by the Infectious Diseases Society of America on the management of bacterial meningitis [Tunkel et al, 2004], and a consensus statement from the British Infection Society on the investigation, treatment, and prevention of acute bacterial meningitis in immunocompetent adults [Begg et al, 1999]:

No prospective case-controlled studies were identified on the potential benefit of pre-hospital antibiotic treatment.

No randomized controlled trials (RCTs) were found to determine the outcome of bacterial meningitis based on the timing of antibiotic administration.

Meningococcal septicaemia

CKS found no studies which examine the effect of pre-hospital antibiotic treatment in people with suspected meningococcal septicaemia.

As identified by NICE [National Collaborating Centre for Women's and Children's Health, 2010], all the evidence identified related to people with suspected meningococcal disease (see below).

Meningococcal disease

In the clinical guideline Bacterial meningitis and meningococcal septicaemia published by NICE [National Collaborating Centre for Women's and Children's Health, 2010; NICE, 2010a], the recommendation to give pre-admission antibiotics is in line with earlier advice issued by the Chief Medical Officer [CMO, 1999], taking into account other NICE and national guidelines (including an earlier guidance from the Health Protection Agency [HPA]) [HPA, 2006; NICE, 2007; SIGN, 2008]. No high-quality evidence was found. Of the five studies identified, the NICE Guideline Development Group was not able to draw any conclusions about whether pre-hospital parenteral antibiotics affect mortality or morbidity.

One systematic review (search date: up to January 2005) found 12 observational cohort studies involving the use of pre-admission parenteral antibiotics [Hahne et al, 2006]. Eight studies showed a beneficial effect, while four found an adverse effect. In seven studies where the patients were seen in primary care, meta-analysis was not possible owing to significant heterogeneity.

Also published in 2006, a UK retrospective case-control study (in 158 children with meningococcal disease) found that compared with the non-antibiotic group, pre-admission parenteral penicillin administered by a GP was associated with increased risk of death, complications in survivors, and more severe disease on admission [Harnden et al, 2006].

A Cochrane systematic review (search date: up to February 2007) found 'no reliable evidence to support or refute the use of pre-admission antibiotics for suspected cases of meningococcal disease' [Sudarsanam et al, 2008]. Only one Nigerian, open-label RCT comparing ceftriaxone and chloramphenicol met inclusion criteria. For further information, see the evidence section on Antibiotic choice.

A Norwegian retrospective review of hospital records (involving 293 people of all ages admitted with meningococcal disease to an university hospital) found no significant difference in mortality between people who received pre-hospital antibiotics (7 out of 63 people died, mortality rate 11%, route of administration unspecified) and those who did not received pre-hospital antibiotic treatment (17 out of 230 people died, mortality rate 7%) (p = 0.34) [Smith et al, 2006].

A Spanish retrospective cohort study (in 848 people diagnosed with invasive meningococcal disease in 31 hospitals in Andalusia and the Canary Islands between 1995 to 2000) concluded that pre-hospital oral antibiotic treatment (given to 226 people, mainly a beta-lactam antibiotic during the previous 48 hours) has a significant protective factor after adjusting the association between the use of antibiotics and death for age, time between onset of symptoms and in-hospital antibiotic treatment (Odds Ratio for death 0.37, 95% Cl 0.15 to 0.93) [Perea-Milla et al, 2009].

The NICE recommendation has been adopted in the updated guidance from the HPA on the public health management of meningococcal disease in the UK [HPA, 2011]. They have been extrapolated to cover both adults and children. No discussion of the evidence was presented.

In the previous version of this guidance, the recommendation to offer pre-hospital antibiotic treatment was based on expert opinion [HPA, 2006]. Evidence from RCTs was lacking. It warned that results from retrospective and observational studies should be interpreted with caution as they do not adequately control for important confounding factors, such as speed of disease progression and stage of illness at the time of treatment.

Other guideline groups that recommend the pre-admission use of parenteral antibiotics (benzylpenicillin first line) in people with suspected meningococcal disease include those by the British Society for the Study of Infection [BSSI, 1995], the Chief Medical Officer (CMO) [CMO, 1995; CMO, 1997; CMO, 1999], the Public Health Laboratory Services (PHLS) [PHLS Meningococcal Infections Working Party, 1995], the British Infection Society [Begg et al, 1999], and the Meningitis Research Foundation [Meningitis Research Foundation, 2008a].

Antibiotic choice

Evidence on antibiotic choice for pre-admission administration for people with suspected meningococcal disease

The evidence from randomized controlled trials on the choice of pre-hospital antibiotic for suspected meningococcal disease is poor. A Cochrane systematic review only identified one study which compared ceftriaxone with chloramphenicol. However, this was undertaken during an epidemic of meningococcal infection in Nigeria and is unlikely to be generalizable to UK primary care practice.

A Cochrane systematic review (search date: up to February 2007) investigated the use of pre-admission antibiotics for people with suspected meningococcal disease [Sudarsanam et al, 2008]. It found 'no reliable evidence to support or refute the use of pre-admission antibiotics for suspected cases of meningococcal disease'.

No randomized controlled trials (RCTs) were found comparing an antibiotic with placebo, or comparing an antibiotic with no intervention.

Of the 30 studies identified, all but one were excluded. Excluded studies included 14 studies identified in a systematic review [Hahne et al, 2006], as these were all cohort studies not RCTs.

Only one open-label, randomized controlled trial met the inclusion criteria [Nathan et al, 2005]. In Nigeria, 510 people with suspected meningococcal meningitis (2 months of age and older, of which 349 were confirmed cases), were randomized to receive ceftriaxone (251 people) or chloramphenicol (259 people), both given as a single intramuscular injection. No significant difference was found in the following outcomes:

Mortality (within 72 hours): risk ratio (RR) 1.20, 95% CI 0.57 to 2.55 (based on outcomes of 510 people).

Neurological complications: RR 1.17, 95% CI 0.63 to 2.20 (based on outcomes of 484 people).

Clinical failure (a composite outcome comprising state of consciousness/neurological status, persistent convulsions, and fever): RR 0.82, 95% CI 0.36 to 1.84 (based on outcomes of 484 people).

Neither treatment was associated with adverse effects.

However, this result should be interpreted with caution, as this study was undertaken during an epidemic of meningococcal infection in Nigeria and is unlikely to be generalizable to UK primary care practice.

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of Bacterial meningitis/meningococcal septicaemia.

Search dates

Dates not restricted – Oct 2010

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

exp Meningitis/, meningitis.tw, exp Meningococcal Infections/

Table 1 . Key to search terms.
Search commands Explanation
/ indicates a MeSh subject heading with all subheadings selected
.tw indicates a search for a term in the title or abstract
exp indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree
$ indicates that the search term was truncated (e.g. wart$ searches for wart and warts)
Sources of guidelines

National Institute for Health and Care Excellence (NICE)

Scottish Intercollegiate Guidelines Network (SIGN)

NICE Evidence

National Guidelines Clearinghouse

New Zealand Guidelines Group

British Columbia Medical Association

Canadian Medical Association

Institute for Clinical Systems Improvement

Guidelines International Network

National Library of Guidelines

National Health and Medical Research Council (Australia)

Alberta Medical Association

University of Michigan Medical School

Michigan Quality Improvement Consortium

Royal College of Nursing

Singapore Ministry of Health

Royal Australian College of General Practitioners

Health Protection Agency

National Resource for Infection Control

CREST

World Health Organization

NHS Scotland National Patient Pathways

Agency for Healthcare Research and Quality

TRIP database

Patient UK Guideline links

UK Ambulance Service Clinical Practice Guidelines

RefHELP NHS Lothian Referral Guidelines

Medline (with guideline filter)

Driver and Vehicle Licensing Agency

Sources of systematic reviews and meta-analyses

The Cochrane Library :

Systematic reviews

Protocols

Database of Abstracts of Reviews of Effects

Medline (with systematic review filter)

EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

NIHR Health Technology Assessment programme

The Cochrane Library :

NHS Economic Evaluations

Health Technology Assessments

Canadian Agency for Drugs and Technologies in Health

International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

The Cochrane Library :

Central Register of Controlled Trials

Medline (with randomized controlled trial filter)

EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Bandolier

Drug & Therapeutics Bulletin

MeReC

NPCi

BMJ Clinical Evidence

DynaMed

TRIP database

Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

Department of Health

Health Management Information Consortium (HMIC)

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

British National Formulary (BNF)

electronic Medicines Compendium (eMC)

European Medicines Agency (EMEA)

LactMed

Medicines and Healthcare products Regulatory Agency (MHRA)

REPROTOX

Scottish Medicines Consortium

Stockley's Drug Interactions

TERIS

TOXBASE

Micromedex

UK Medicines Information

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