Bacterial meningitis

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    Meningitis is an acute bacterial infection of the meninges, which may affect the brain and lead to irreversible neurological damage and auditory impairment.
    Bacterial meningitis is a medical emergency. The treatment is based on early parenteral administration of antibiotics that penetrates well into the cerebrospinal fluid (CSF). Empiric antibiotic therapy is administered if the pathogen cannot be identified or while waiting for laboratory results.
    The main bacteria responsible vary depending on age and/or context:

    Meningitis in a non-epidemic context

    • Children 0 to 3 months:
      • Children ≤ 7 days: Gram-negative bacilli (Klebsiella spp, E. coli, S. marcescens, Pseudomona spp, Salmonella spp) and group B streptococcus
      • Children > 7 days: S. pneumoniae accounts for 50% of all bacterial meningitis

    L. monocytogenes is occasionally responsible for meningitis during this period.

    • Children 3 months-5 years: S. pneumoniae, H. influenza B and N. meningitidis
    • Children > 5 years and adults: S. pneumoniae and N. meningitidis

     

    Special conditions:

    • Immunodepressed patients (HIV, malnourished): high percentage of Gram- negative bacilli (specially Salmonella spp) and also M. tuberculosis.
    • Sickle cell anaemia: Salmonella spp and Staphylococcus aureus are frequent causes.
    • Meningitis may be related to S. aureus when associated with skin infection or skull fracture.

    Meningitis in an epidemic context

    In the Sahelian region (but not exclusively, e.g. Rwanda, Angola, Brazil), during the dry season, epidemics of meningococcal meningitis (Neisseria meningitidis A or C or W135) affect children from 6 months of age, adolescents and adults. In these regions, whether during epidemics or not, all the above pathogens can be found, especially in young children.

    Clinical features

    The clinical presentation depends on the patient's age.

    Children over 1 year and adults

    • Fever, severe headache, photophobia, neck stiffness
    • Brudzinski's sign (neck flexion in a supine patient results in involuntary flexion of the knees) and Kernig's sign (attempts to extend the knee from the flexed-thigh position are met with strong passive resistance).
    • Petechial or ecchymotic purpura (usually in meningococcal infections)
    • In severe forms: coma, seizures, focal signs, purpura fulminans

    Children under 1 year

    The classic signs of meningitis are usually absent.

    • The child is irritable, appears sick with fever or hypothermia, poor feeding or vomiting.
    • Other features include: seizures, apnoea, altered consciousness, bulging fontanelle (when not crying); occasionally, neck stiffness and purpuric rash.

    Laboratory

    • Lumbar puncture (LP):
      • Macroscopic examination of CSF: antibiotic therapy should be initiated immediately if the LP yields a turbid CSF.
      • Microscopic examination: Gram stain (but a negative examination does not exclude the diagnosis) and white blood cell count (WBC).
      • In an epidemic context, once the meningococcal aetiology has been confirmed, there is no need for routine LP for new cases.

     

    Pressure

    Aspect

    WBC
    (leucocytes/mm3)

    Protein

    Other tests

    Normal CSF

     

    Clear

    < 5

    Pandy–
    < 40 mg/dl

    –

    Bacterial meningitis

    ++++

    Cloudy, turbid

    100-20 000
    mainly neutrophiles

    In neonates:
    > 20

    In immunocompromised,
    the WBC may be < 100

    Pandy+
    100-500 mg/dl

    Gram stain +

    Viral meningitis

    Normal to +

    Clear

    10-700
    mainly lymphocytes

    Pandy–

    –

    TB meningitis

    +++

    Clear or yellowish

    < 500
    mainly lymphocytes

    Pandy+

    AFB

    Cryptococcal meningitis

    ++++

    Clear

    < 800
    mainly lymphocytes

    Pandy–

    India ink

     

    • Rapid test for detection of bacterial antigens.

     

    Note: in an endemic area, it is essential to test for severe malaria (rapid test or thin/thick films).

    Treatment in a non-epidemic context

    Antibiotic therapy

    For the choice of antibiotic therapy and dosages according to age, see table below.

     

      No associated skin infection Associated skin infection (including umbilical cord infection)

     

    First line

    Alternative

    First line

    Alternative

    0 to 7 days
    < 2 kg

    ampicillin IV
    100 mg/kg every 12 hours
    +
    cefotaxime IV
    50 mg/kg every 12 hours

    ampicillin IV
    100 mg/kg every 12 hours
    +
    gentamicin IV
    3 mg/kg once daily

    cloxacillin IV
    50 mg/kg every 12 hours
    +
    cefotaxime IV
    50 mg/kg every 12 hours

    cloxacillin IV
    50 mg/kg every 12 hours
    +
    gentamicin IV
    3 mg/kg once daily

    0 to 7 days
    ≥ 2 kg

    ampicillin IV
    100 mg/kg every 8 hours
    +
    cefotaxime IV
    50 mg/kg every 8 hours

    ampicillin IV
    100 mg/kg every 8 hours
    +
    gentamicin IV
    5 mg/kg once daily

    cloxacillin IV
    50 mg/kg every 8 hours
    +
    cefotaxime IV
    50 mg/kg every 8 hours

    cloxacillin IV
    50 mg/kg every 8 hours
    +
    gentamicin IV
    5 mg/kg once daily

    8 days to
    < 1 month
    ≥ 2 kg

    ampicillin IV
    100 mg/kg every 8 hours
    +
    cefotaxime IV
    50 mg/kg every 8 hours

    ampicillin IV
    100 mg/kg every 8 hours
    +
    gentamicin IV
    5 mg/kg once daily

    cloxacillin IV
    50 mg/kg every 6 hours
    +
    cefotaxime IV
    50 mg/kg every 8 hours

    cloxacillin IV
    50 mg/kg every 6 hours
    +
    gentamicin IV
    5 mg/kg once daily

    1 to 3 months

    ampicillin IV
    100 mg/kg every 8 hours
    +
    ceftriaxone IV 100 mg/kg on D1
    then starting on D2: 100 mg/kg once daily or 50 mg/kg every 12 hours

    ampicillin IV
    100 mg/kg every 8 hours
    +
    gentamicin IV
    2.5 mg/kg every 8 hours

    cloxacillin IV
    50 mg/kg every 6 hours
    +
    ceftriaxone IV 100 mg/kg on D1
    then starting on D2: 100 mg/kg once daily or 50 mg/kg every 12 hours

    cloxacillin IV
    50 mg/kg every 6 hours
    +
    gentamicin IV
    2.5 mg/kg every 8 hours
    > 3 months

    ceftriaxone IV
    Children: 100 mg/kg on D1 then starting on D2: 100 mg/kg once daily or 50 mg/kg every 12 hours (max. 4 g daily)

    cloxacillin IV
    Children < 40 kg: 50 mg/kg every 6 hours
    Children ≥ 40 kg: 2 g every 6 hours
    +
    ceftriaxone IV
    Children: 100 mg/kg on D1 then starting on D2: 100 mg/kg once daily or 50 mg/kg every 12 hours (max. 4 g daily)
    Adults ceftriaxone IV: 4 g once daily or 2 g every 12 hours cloxacillin IV: 2 g every 6 hours
    +
    ceftriaxone IV: 4 g once daily or 2 g every 12 hours


    Duration of antibiotherapy:

     

    1) According to the pathogen:

    • Haemophilus influenzae: 7 days
    • Streptococcus pneumonia: 10-14 days
    • Group B streptococcus and Listeria: 14-21 days
    • Gram-negative bacilli: 21 days
    • Neisseria meningitidis: see antibiotherapy in an epidemic context

     

    2) If the pathogen is unknown:

    • Children < 3 months: 2 weeks beyond the first sterile CSF culture or 21 days
    • Children > 3 months and adults: 10 days. Consider extending treatment or alternative diagnoses if fever persists beyond 10 days. On the other hand, a 7-day course of ceftriaxone is sufficient in patients who are making an uncomplicated recovery.

    Additional treatment

    • Dexamethasone reduces the risk of hearing loss in patients with H. influenzae or S. pneumoniae.
      Early administration is indicated in meningitis caused by these pathogens or when the pathogen is unknown, except in neonates (and in presumed meningococcal meningitis in an epidemic context).
      dexamethasone IV [1] Citation 1. D. van de Beek, C. Cabellos, O. Dzupova, S. Esposito, M. Klein, A. T. Kloek, S. L. Leib, B. Mourvillier, C. Ostergaard, P. Pagliano, H.W. Pfister, R. C. Read, O. Resat Sipahi, M.C. Brouwer. ESCMID guideline: diagnosis and treatment of acute bacterial meningitis, 2016.
      https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(16)00020-3/pdf             [2] Citation 2. Sheldon L Kaplan, MD. Bacterial meningitis in children: Dexamethasone and other measures to prevent neurologic complications. UpToDate [Accessed 25 February 2019].
      Children > 1 month: 0.15 mg/kg (max. 10 mg) every 6 hours for 2 to 4 days
      Adults: 10 mg every 6 hours for 2 to 4 days
      The treatment should be started before or with the first dose of antibiotic, otherwise, the treatment offers no benefit.
    • Ensure that the patient is well fed and well hydrated (infusions or nasogastric tube if necessary).
    • Seizures (Chapter 1).
    • Coma: prevention of bed sores, care of the mouth and eyes, etc.

    Treatment in an epidemic context

    Antibiotic therapy

    In this context, N. meningitidis is the most likely pathogen.

     

    Age Treatment [3] Citation 3. World Health Organization. Managing meningitis epidemics in Africa. A quick reference guide for health authorities and health-care workers. 2015.
    https://apps.who.int/iris/bitstream/handle/10665/154595/WHO_HSE_GAR_ERI_2010.4_Rev1_eng.pdf?sequence=1

    Children
    < 2 months

    ceftriaxone IV (a) Citation a. The solvent of ceftriaxone for IM injection contains lidocaine. Ceftriaxone reconstituted using this solvent must never be administered by IV route. For IV administration, water for injection must always be used.  or IM (b) Citation b. For IM administration, divide the dose into 2 injections if needed, half-dose in each buttock.  for 7 days

    100 mg/kg once daily 

    Children ≥ 2 months
    and adults

    ceftriaxone IV (a) Citation a. The solvent of ceftriaxone for IM injection contains lidocaine. Ceftriaxone reconstituted using this solvent must never be administered by IV route. For IV administration, water for injection must always be used.  or IM (b) Citation b. For IM administration, divide the dose into 2 injections if needed, half-dose in each buttock.  or 5 days
    Children 2 months to < 5 years: 100 mg/kg once daily (max. 2 g daily)
    Children ≥ 5 years and adults: 2 g once daily

    Note:
    A short treatment with a single dose of ceftriaxone IM can be used in children 2 years and older and in adults during a meningococcal meningitis epidemic if 1) confirmed by a reliable laboratory 2) the number of cases exceeds management capacities with the 5-day treatment. Check national recommendations. Nevertheless, it is essential to ensure a monitoring of cases after 24 hours.
    ceftriaxone IM a Citation a. For IM administration, divide the dose into 2 injections if needed, half-dose in each buttock.
    Children 2 to < 12 years: 100 mg/kg single dose
    Children ≥ 12 years and adults: 4 g single dose
    If there is no clinical improvement (fever > 38.5 °C, repeated seizures, appearance or aggravation of a reduced level of consciousness or of neurological signs) 24 hours after the injection, continue the treatment with ceftriaxone for 5 days.

    Additional treatment

    • Ensure that the patient is well fed and well hydrated (infusions or nasogastric tube if necessary).
    • Seizures (Chapter 1).
    • Coma: prevention of bed sores, care of the mouth and eyes, etc.
    • Dexamethasone in not indicated.

     

    Footnotes
    • (a)For IM administration, divide the dose into 2 injections if needed, half-dose in each buttock.
    • (a) The solvent of ceftriaxone for IM injection contains lidocaine. Ceftriaxone reconstituted using this solvent must never be administered by IV route. For IV administration, water for injection must always be used.
    • (b) For IM administration, divide the dose into 2 injections if needed, half-dose in each buttock.
    References
    Path