Investigation and management in children and young people with petechial rash

• Give intravenous ceftriaxone immediately to children and young people with a petechial rash if any of the following occur at any point during the assessment (these children are at high risk of having meningococcal disease):

  –

  petechiae start to spread

  –

  the rash becomes purpuric

  –

  there are signs of bacterial meningitis (see table 1)

  –

  there are signs of meningococcal septicaemia (see table 1)

  –

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

Polymerase chain reaction

• Perform whole blood real-time polymerase chain reaction testing (EDTA^[1] sample) for N meningitidis to confirm a diagnosis of meningococcal disease.

Lumbar puncture

• In children and young people with suspected meningitis or suspected meningococcal disease, perform a lumbar puncture unless any of the following contraindications are present:

  –

  signs suggesting raised intracranial pressure

  ◇

  reduced or fluctuating level of consciousness (Glasgow Coma Scale score less than 9 or a drop of 3 or more)

  ◇

  relative bradycardia and hypertension

  ◇

  focal neurological signs

  ◇

  abnormal posture or posturing

  ◇

  unequal, dilated or poorly responsive pupils

  ◇

  papilloedema

  ◇

  abnormal ‘doll’s eye’ movements

  –

  shock (see table 1)

  –

  extensive or spreading purpura

  –

  after convulsions until stabilised

  –

  coagulation abnormalities

  ◇

  coagulation results (if obtained) outside the normal range

  ◇

  platelet count below 100 × 10⁹/litre

  ◇

  receiving anticoagulant therapy

  –

  local superficial infection at the lumbar puncture site

  –

  respiratory insufficiency (lumbar puncture is considered to have a high risk of precipitating respiratory failure in the presence of respiratory insufficiency).

Fluids for bacterial meningitis

• Do not restrict fluids unless there is evidence of:

  –

  raised intracranial pressure, or

  –

  increased antidiuretic hormone secretion^[2].

Intravenous fluid resuscitation in meningococcal septicaemia

• In children and young people with suspected or confirmed meningococcal septicaemia:

  –

  if there are signs of shock give an immediate fluid bolus of 20 ml/kg sodium chloride 0.9% over 5–10 minutes. Give the fluid intravenously or via an intraosseous route and reassess the child or young person immediately afterwards

  –

  if the signs of shock persist, immediately give a second bolus of 20 ml/kg of intravenous or intraosseous sodium chloride 0.9% or human albumin 4.5% solution over 5–10 minutes

  –

  if the signs of shock still persist after the first 40 ml/kg:

  ◇

  immediately give a third bolus of 20 ml/kg of intravenous or intraosseous sodium chloride 0.9% or human albumin 4.5% solution over 5–10 minutes

  ◇

  call for anaesthetic assistance for urgent tracheal intubation and mechanical ventilation

  ◇

  start treatment with vasoactive drugs

  ◇

  be aware that some children and young people may require large volumes of fluid over a short period of time to restore their circulating volume

  ◇

  consider giving further fluid boluses at 20 ml/kg of intravenous or intraosseous

  ◇

  sodium chloride 0.9% or human albumin 4.5% solution over 5–10 minutes based on clinical signs and appropriate laboratory investigations including urea and electrolytes

  –

  discuss further management with a paediatric intensivist.

Long-term effects of bacterial meningitis and meningococcal septicaemia

• Offer children and young people with a severe or profound deafness an urgent assessment for cochlear implants as soon as they are fit to undergo testing (further guidance on the use of cochlear implants for severe to profound deafness can be found in the NICE technology appraisal guidance on cochlear implants for children and adults with severe to profound deafness).
• Children and young people should be reviewed by a paediatrician with the results of their hearing test 4–6 weeks after discharge from hospital to discuss morbidities associated with their condition and offered referral to the appropriate services. The following morbidities should be specifically considered:

  –

  hearing loss (with the child or young person having undergone an urgent assessment for cochlear implants as soon as they are fit)

  –

  orthopaedic complications (damage to bones and joints)

  –

  skin complications (including scarring from necrosis)

  –

  psychosocial problems

  –

  neurological and developmental problems

  –

  renal failure.

Suspected bacterial meningitis without non-blanching rash

1.2.2.

Transfer children and young people with suspected bacterial meningitis without non-blanching rash directly to secondary care without giving parenteral antibiotics.

1.2.3.

If urgent transfer to hospital is not possible (for example, in remote locations or adverse weather conditions), administer antibiotics to children and young people with suspected bacterial meningitis.

Suspected meningococcal disease (meningitis with non-blanching rash or meningococcal septicaemia)

1.2.4.

Give parenteral antibiotics (intramuscular or intravenous benzylpenicillin) at the earliest opportunity, either in primary or secondary care, but do not delay urgent transfer to hospital to give the parenteral antibiotics.

1.2.5.

Withhold benzylpenicillin only in children and young people who have a clear history of anaphylaxis after a previous dose; a history of a rash following penicillin is not a contraindication.

Investigation and management in children and young people with petechial rash

1.3.2.

Give intravenous ceftriaxone immediately to children and young people with a petechial rash if any of the following occur at any point during the assessment (these children are at high risk of having meningococcal disease):

• petechiae start to spread
• the rash becomes purpuric
• there are signs of bacterial meningitis (see table 1)
• there are signs of meningococcal septicaemia (see table 1)
• the child or young person appears ill to a healthcare professional.

1.3.3.

If a child or young person has an unexplained petechial rash and fever (or history of fever) carry out the following investigations:

• full blood count
• C-reactive protein (CRP)
• coagulation screen
• blood culture
• whole-blood polymerase chain reaction (PCR) for N meningitidis
• blood glucose
• blood gas.

1.3.4.

In a child or young person with an unexplained petechial rash and fever (or history of fever) but none of the high-risk clinical manifestations (see table 1):

• Treat with intravenous ceftriaxone immediately if the CRP and/or white blood cell count (especially neutrophil count) is raised, as this indicates an increased risk of having meningococcal disease.
• Be aware that while a normal CRP and normal white blood cell count mean meningococcal disease is less likely, they do not rule it out. The CRP may be normal and the white blood cell count normal or low even in severe meningococcal disease.
• Assess clinical progress by monitoring vital signs (respiratory rate, heart rate, blood pressure, conscious level [Glasgow Coma Scale and/or APVU], temperature), capillary refill time, and oxygen saturations. Carry out observations at least hourly over the next 4–6 hours.
• If doubt remains, treat with antibiotics and admit to hospital.

1.3.5.

If the child or young person is assessed as being at low risk of meningococcal disease and is discharged after initial observation, advise parents or carers to return to hospital if the child or young person appears ill to them.

1.3.6.

Be aware that in children and young people who present with a non-spreading petechial rash without fever (or history of fever) who do not appear ill to a healthcare professional, meningococcal disease is unlikely, especially if the rash has been present for more than 24 hours. In such cases consider:

• other possible diagnoses
• performing a full blood count and coagulation screen.

Investigation and management in children and young people with suspected bacterial meningitis

1.3.7.

In children and young people with suspected bacterial meningitis, perform a CRP and white blood cell count:

• If the CRP and/or white blood cell count is raised and there is a non-specifically abnormal cerebrospinal fluid (CSF) (for example consistent with viral meningitis), treat as bacterial meningitis.
• Be aware that a normal CRP and white blood cell count does not rule out bacterial meningitis.
• Regardless of the CRP and white blood cell count, if no CSF is available for examination or if the CSF findings are uninterpretable, manage as if the diagnosis of meningitis is confirmed.

Polymerase chain reaction (PCR) tests for bacterial meningitis and meningococcal disease

1.3.8.

Perform whole blood real-time PCR testing (EDTA^[8] sample) for N meningitidis to confirm a diagnosis of meningococcal disease.

1.3.9.

The PCR blood sample should be taken as soon as possible because early samples are more likely to be positive.

1.3.10.

Use PCR testing of blood samples from other hospital laboratories if available, to avoid repeating the test.

1.3.11.

Be aware that a negative blood PCR test result for N meningitidis does not rule out meningococcal disease.

1.3.12.

Submit CSF to the laboratory to hold for PCR testing for N meningitidis and S pneumoniae, but only perform the PCR testing if the CSF culture is negative.

1.3.13.

Be aware that CSF samples taken up to 96 hours after admission to hospital may give useful results.

Skin samples for meningococcal disease

1.3.14.

Do not use any of the following techniques when investigating for possible meningococcal disease: skin scrapings, skin biopsies, petechial or purpuric lesion aspirates (obtained with a needle and syringe).

Performing lumbar puncture and interpreting CSF parameters for suspected bacterial meningitis

1.3.15.

Perform a lumbar puncture as a primary investigation unless this is contraindicated.

1.3.16.

Do not allow lumbar puncture to delay the administration of parenteral antibiotics.

1.3.17.

CSF examination should include white blood cell count and examination, total protein and glucose concentrations, Gram stain and microbiological culture. A corresponding laboratory-determined blood glucose concentration should be measured.

1.3.18.

In children and young people with suspected meningitis or suspected meningococcal disease, perform a lumbar puncture unless any of the following contraindications are present:

• signs suggesting raised intracranial pressure

  –

  reduced or fluctuating level of consciousness (Glasgow Coma Scale score less than 9 or a drop of 3 or more)

  –

  relative bradycardia and hypertension

  –

  focal neurological signs

  –

  abnormal posture or posturing

  –

  unequal, dilated or poorly responsive pupils

  –

  papilloedema

  –

  abnormal ‘doll’s eye’ movements

• shock (see table 1)
• extensive or spreading purpura
• after convulsions until stabilised
• coagulation abnormalities

  –

  coagulation results (if obtained) outside the normal range

  –

  platelet count below 100 × 10⁹/litre

  –

  receiving anticoagulant therapy

• local superficial infection at the lumbar puncture site
• respiratory insufficiency (lumbar puncture is considered to have a high risk of precipitating respiratory failure in the presence of respiratory insufficiency).

1.3.19.

In children and young people with suspected bacterial meningitis, if contraindications to lumbar puncture exist at presentation consider delaying lumbar puncture until there are no longer contraindications. Delayed lumbar puncture is especially worthwhile if there is diagnostic uncertainty or unsatisfactory clinical progress.

1.3.20.

CSF white blood cell counts, total protein and glucose concentrations should be made available within 4 hours to support the decision regarding adjunctive steroid therapy.

1.3.21.

Start antibiotic treatment for bacterial meningitis if the CSF white blood cell count is abnormal:

• in neonates at least 20 cells/microlitre (be aware that even if fewer than 20 cells/microlitre, bacterial meningitis should still be considered if other symptoms and signs are present – see table 1)
• in older children and young people more than 5 cells/microlitre or more than 1 neutrophil/microlitre, regardless of other CSF variables.

1.3.22.

In children and young people with suspected bacterial meningitis, consider alternative diagnoses if the child or young person is significantly ill and has CSF variables within the accepted normal ranges.

1.3.23.

Consider herpes simplex encephalitis as an alternative diagnosis.

1.3.24.

If CSF white cell count is increased and there is a history suggesting a risk of tuberculous meningitis, evaluate for the diagnosis of tuberculous meningitis in line with the NICE guideline on tuberculosis.

1.3.25.

Perform a repeat lumbar puncture in neonates with:

• persistent or re-emergent fever
• deterioration in clinical condition
• new clinical findings (especially neurological findings) or
• persistently abnormal inflammatory markers.

1.3.26.

Do not perform a repeat lumbar puncture in neonates:

• who are receiving the antibiotic treatment appropriate to the causative organism and are making a good clinical recovery
• before stopping antibiotic therapy if they are clinically well.

Cranial computed tomography in suspected bacterial meningitis

1.3.27.

Use clinical assessment and not cranial computed tomography (CT), to decide whether it is safe to perform a lumbar puncture. CT is unreliable for identifying raised intracranial pressure.

1.3.28.

If a CT scan has been performed, do not perform a lumbar puncture if the CT scan shows radiological evidence of raised intracranial pressure.

1.3.29.

In children and young people with a reduced or fluctuating level of consciousness (Glasgow Coma Scale score less than 9 or a drop of 3 or more) or with focal neurological signs, perform a CT scan to detect alternative intracranial pathology.

1.3.30.

Do not delay treatment to undertake a CT scan.

1.3.31.

Clinically stabilise children and young people before CT scanning.

1.3.32.

If performing a CT scan consult an anaesthetist, paediatrician or intensivist.

Antibiotics for suspected bacterial meningitis or meningococcal disease

1.4.1.

Treat children and young people aged 3 months or older with suspected bacterial meningitis without delay using intravenous ceftriaxone.

1.4.2.

Treat children younger than 3 months with suspected bacterial meningitis without delay using intravenous cefotaxime plus either amoxicillin or ampicillin.

1.4.3.

Treat suspected meningococcal disease without delay using intravenous ceftriaxone.

1.4.4.

Treat children and young people with suspected bacterial meningitis who have recently travelled outside the UK or have had prolonged or multiple exposure to antibiotics (within the past 3 months) with vancomycin in addition to the above antibiotics.

1.4.5.

If calcium-containing infusions are being administered, do not use ceftriaxone. Instead, use cefotaxime^[9].

1.4.6.

In children younger than 3 months, ceftriaxone may be used as an alternative to cefotaxime (with or without ampicillin or amoxicillin), but be aware that ceftriaxone should not be used in premature babies or in babies with jaundice, hypoalbuminaemia or acidosis as it may exacerbate hyperbilirubinaemia.

1.4.7.

If tuberculous meningitis is part of the differential diagnosis use antibiotic treatment appropriate for tuberculous meningitis in line with the NICE guideline on tuberculosis.

1.4.8.

If herpes simplex meningoencephalitis is part of the differential diagnosis give appropriate antiviral treatment.

Treatment for specific infections in confirmed bacterial meningitis

Treatment of unconfirmed bacterial meningitis

1.4.14.

In children and young people aged 3 months or older with unconfirmed, uncomplicated but clinically suspected bacterial meningitis, treat with intravenous ceftriaxone for at least 10 days depending on symptoms and signs and course of the illness.

1.4.15.

In children younger than 3 months with unconfirmed but clinically suspected bacterial meningitis, treat with cefotaxime plus either ampicillin or amoxicillin for at least 14 days. If the clinical course is complicated^[10], consider extending the duration of treatment and consulting an expert in paediatric infectious diseases.

Meningococcal disease

1.4.16.

In children and young people with confirmed meningococcal disease, treat with intravenous ceftriaxone for 7 days in total unless directed otherwise by the results of antibiotic sensitivities.

1.4.17.

In children and young people with unconfirmed but clinically suspected meningococcal disease, treat with intravenous ceftriaxone for 7 days in total.

Other aspects of management in bacterial meningitis and meningococcal septicaemia

Corticosteroids

Adjunctive therapies

1.4.46.

Do not use activated protein C or recombinant bacterial permeability-increasing protein in children and young people with meningococcal septicaemia.

Monitoring for deterioration for meningococcal disease

1.4.47.

Monitor children and young people closely after admission to hospital for signs of deterioration (monitor respiration, pulse, blood pressure, oxygen saturation and Glasgow Coma Scale score).

1.4.48.

Be aware that children and young people with meningococcal disease can deteriorate rapidly, regardless of the results of any initial assessment of severity.

Retrieval and transfer to tertiary care

1.4.49.

Children and young people who need resuscitation should be discussed with a paediatric intensivist as soon as possible.

1.4.50.

Transfer of children and young people to tertiary care should be undertaken by an experienced paediatric intensive care retrieval team comprising medical and nursing staff.

Long-term effects of bacterial meningitis and meningococcal septicaemia

1.5.1.

Before discharging children and young people from hospital:

• consider their requirements for follow-up, taking into account potential sensory, neurological, psychosocial, orthopaedic, cutaneous and renal morbidities, and
• discuss potential long-term effects of their condition and likely patterns of recovery with the child or young person and their parents or carers, and provide them with opportunities to discuss issues and ask questions.

1.5.2.

Offer children and young people and their parents or carers:

• information about and access to further care immediately after discharge, and
• contact details of patient support organisations including meningitis charities that can offer support, befriending, in-depth information, advocacy, counselling, and written information to signpost families to further help, and
• advice on accessing future care.

1.5.3.

Offer a formal audiological assessment as soon as possible, preferably before discharge, within 4 weeks of being fit to test.

1.5.4.

Offer children and young people with a severe or profound deafness an urgent assessment for cochlear implants as soon as they are fit to undergo testing (further guidance on the use of cochlear implants for severe to profound deafness can be found in the NICE technology appraisal guidance on cochlear implants for children and adults with severe to profound deafness).

1.5.5.

Children and young people should be reviewed by a paediatrician with the results of their hearing test 4–6 weeks after discharge from hospital to discuss morbidities associated with their condition and offered referral to the appropriate services. The following morbidities should be specifically considered:

• hearing loss (with the child or young person having undergone an urgent assessment for cochlear implants as soon as they are fit)
• orthopaedic complications (damage to bones and joints)
• skin complications (including scarring from necrosis)
• psychosocial problems
• neurological and developmental problems
• renal failure.

1.5.6.

Inform the child’s or young person’s GP, health visitor and school nurse (for school-age children and young people) about their bacterial meningitis or meningococcal septicaemia.

1.5.7.

Healthcare professionals with responsibility for monitoring the child’s or young person’s health should be alert to possible late-onset sensory, neurological, orthopaedic and psychosocial effects of bacterial meningitis and meningococcal septicaemia.

Immune testing

1.5.8.

Test children and young people for complement deficiency if they have had either:

• more than one episode of meningococcal disease, or
• one episode of meningococcal disease caused by serogroups other than B (for example A, C, Y, W135, X, 29E), or
• meningococcal disease caused by any serogroup and a history of other recurrent or serious bacterial infections.

1.5.9.

Children and young people with recurrent episodes of meningococcal disease should be assessed by a specialist in infectious disease or immunology.

1.5.10.

Do not test children and young people for complement deficiency who have had either:

• a single episode of meningococcal disease caused by serogroup B meningococcus, or
• unconfirmed meningococcal disease.

1.5.11.

Discuss appropriate testing for complement deficiency with local immunology laboratory staff.

1.5.12.

If a child or young person who has had meningococcal disease has a family history of meningococcal disease or complement deficiency, test the child or young person for complement deficiency.

1.5.13.

If a child or young person who has had meningococcal disease is found to have complement deficiency, test their parents and siblings for complement deficiency.

1.5.14.

Refer children and young people with complement deficiency to a healthcare professional with expertise in the management of the condition.

1.5.15.

Do not test children and young people for immunoglobulin deficiency if they have had meningococcal disease, unless they have a history suggestive of an immunodeficiency (that is, a history of serious, persistent, unusual, or recurrent infections).

Why this is important

Research is needed from primary and secondary care settings on the diagnostic accuracy of symptoms and signs suggestive of bacterial meningitis and meningococcal disease in children and young people. The research should focus on identifying individual symptoms and signs, or groups of symptoms and signs that are effective as predictors of bacterial meningitis and meningococcal disease. These symptoms and signs should also differentiate effectively between these conditions and minor self-limiting infections. The research should include consideration of the effectiveness of symptoms and signs of acute feverish illness as predictors of meningococcal disease. Consideration should also be given to the age of the child or young person (in terms of the relevance of particular symptoms and signs) and the clinical setting at presentation. Suitable study designs would include diagnostic accuracy studies as well as observational studies (such as case–control studies), and the research could include a systematic review of studies that have already been published.

Why this is important

Bacterial meningitis is a rare disease that is not easily distinguishable clinically from aseptic meningitis. It is, however, important to recognise those children who are most likely to have bacterial meningitis to direct appropriate management of the condition and to avoid inappropriate treatment of aseptic meningitis. Since the introduction of vaccines to protect against Hib, meningococcus serogroup C and pneumococcus, no high-quality studies involving previously healthy children and young people have been conducted in the UK to determine normal ranges for blood test results or CSF findings in bacterial and aseptic meningitis. Such studies are needed to provide reference values to help interpret blood test results and CSF findings in children (especially neonates) and young people with suspected bacterial meningitis.

Why this is important

There are theoretical reasons why albumin solution may be more effective than crystalloid solution in children and young people with septic shock. However, no clinical studies have evaluated the effectiveness of albumin solution in children and young people with meningococcal disease. Concerns about the safety of colloids such as albumin solution led to a widespread change in clinical practice in the 1990s to using crystalloid solutions, despite a lack of evidence of equivalent effectiveness. Although albumin solution is considerably more expensive than crystalloid solution, a small additional benefit of albumin over crystalloid (one death prevented in more than 14,000 treated cases) would make the use of albumin solution cost effective. Randomised controlled trials are therefore needed to compare the effectiveness of albumin and crystalloid solutions in children and young people with septic shock.

Why this is important

Neonatal bacterial meningitis is associated with high morbidity, despite the availability of antibiotics that are highly effective against the leading causes of bacterial meningitis in this age group. New approaches to management are needed because there are currently no vaccines to protect against infection from the causative organisms. Corticosteroids are effective as an adjunct to antibiotic treatment in older children with meningitis caused by Hib, and in adults with bacterial meningitis. However, there is insufficient evidence to support a recommendation for adjunctive corticosteroid treatment in neonates. Extrapolation from older age groups would be inappropriate because the spectrum of organisms causing infection in neonates is different, and the impact on the developing brain of the causative organisms during inflammation may not be the same. A large-scale randomised controlled trial is therefore needed to compare the effectiveness of antibiotic treatment plus corticosteroids with antibiotic treatment alone in neonates with suspected or confirmed bacterial meningitis.

Why this is important

Well-conducted but relatively small randomised controlled trials involving adults only suggest that low-dose corticosteroid replacement treatment may ameliorate haemodynamic failure and inflammatory dysregulation associated with severe sepsis. Such treatment may also improve outcomes following septic shock. Severe sepsis in children and young people differs from that in adults, in that multiple-organ dysfunction is less common in children and young people, and mortality is lower. A randomised controlled trial involving children and young people is needed to evaluate the effectiveness of corticosteroid replacement treatment. Studies involving adults suggest that those with normal adrenal function have worse outcomes if they receive steroids than those with adrenal dysfunction, and so the proposed trial should consider whether testing for adrenal dysfunction before starting steroid replacement treatment improves outcomes.