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Bacterial meningitis

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Shunt infection

See also Meningococcal disease

Epidemiology

3 organisms predominate in causing community-acquired bacterial meningitis:

  • Neisseria meningitidis. Most common in childhood but also affects adolescents and adults
  • Haemophilus influenzae. Chiefly children < 5 yrs but occasionally affects older children. Incidence in developed countries has decreased dramatically since the introduction of HIB conjugate vaccines
    Overall mortality from meningococcal and haemophilus meningitis is 5-6% in Britain
  • Streptococcus pneumoniae. All ages but particularly affects patients at the 2 extremes of life. Associated with immune defects such as asplenia (eg sickle cell disease), fractures of skull and congenital defects that allow entry of bacteria to CNS. Carries high mortality, rarely < 20%. Most common pathogen in USA

In nosocomial meningitis gm -ve organisms such as E. coli, Klebsiella, Listeria monocytogenes and pseudomonas need to be considered. Cryptococcal meningitis must be considered in HIV infected patients.

Infections following skull trauma and neurosurgery are frequently caused by Staph. aureus and epidermidis respectively

Pathogenesis and pathophysiology

  • entry to CNS is via haematogenous route
  • factors that result in meningeal localization of bacteria largely unknown. Seem to settle on walls of venous sinuses and vessels with slow blood flow. Subsequently bacteria penetrate dura to enter subarachnoid space
  • release of cytokines and other endogenous mediators then cause an inflammatory response in CNS with vasculitis, infarction, vasogenic oedema, increased permeability of blood brain barrier, raised ICP and decreased cerebral blood flow
  • any infection can seed meninges but typical associated infections are those of upper respiratory tract, pneumonia and otitis media

Picture

Clinical features

  • In most patients diagnosis is obvious from the combination of: malaise, fever, severe headache, photophobia, neck stiffness ± disturbed consciousness.
  • In elderly and infants diagnosis may be difficult. In elderly consciousness may become rapidly depressed and soft neurological signs may be present. However meningism is usually maintained even in comatose patients.
  • ± Kernig’s and Brudzinski’s (flexion of lower limbs in response to neck flexion) signs
  • Meningococcal meningitis may present in several atypical ways:
  • fulminating meningococcal septicaemia may run its short course from onset to death with no element of meningitis
  • may be a period of hours-days of febrile illness with no meningeal features before features of meningitis appear, especially in children
  • acute mania. More common in adolescents and young adults. Neck stiffness may not yet have developed or may be impossible to test for.
  • Combination of petechial-purpuric rash and meningitis is virtually diagnostic for meningococcal meningitis. Note that the rash may consit of only a few inconspicuous petechiae and in early stages may only be a macular, unimpressive rash. Petechiae may occur in other forms of meningitis.
  • Other clinical features:
    • focal neurological signs are relatively uncommon in previously healthy patients
    • ocular palsies usually resolve within days-weeks
    • labyrinthine damage, which often develops early in the illness, is usually permanent
    • convulsions. Frequency varies greatly between the different forms of meningitis. Most frequent in pneumococcal and least in meningococcal. Uncommon in adults with community-acquired meningitis and no underlying CNS abnormality
    • raised intracranial pressure
  • Listeria usually presents as an acute purulent meningitis with no particular distinguishing features but onset may be insidious with malaise, low fever and headache. Neurological signs and disturbance of consciousness are common with a mixed meningitic and encephalitic picture. More common in elderly and immunocompromised.

Investigations

Lumbar puncture

  • Allows early and accurate diagnosis but is associated with a significant risk of coning in some patients. Should be avoided or delayed in adults with the following features, which are associated with an increased risk of herniation:
  • coma or rapidly increasing depression of consciousness
  • focal neurological signs
  • fits
    • fit in last 30 mins
    • prolonged fits
    • new onset fits within 1 week of presentation
  • papilloedema
  • immunosuppression
    • eg HIV infection, immunosuppressive therapy
  • Should not delay urgent treatment of patients with established or threatened bacterial shock (usually meningococcal septicaemia)

  • If there is likely to be a significant delay before performing the lumbar puncture antibiotics should be given first (after obtaining blood cultures)

  • Gram staining of centrifuged CSF deposit is gold standard for early diagnosis. Later CSF and blood cultures provide the main diagnostic yield.

  • CSF findings in meningitis:

    • WCC usually 1000-5000 cells/ml, range <100->10,000. Neutrophil predominant. WCC count lower and less predominantly neutrophils in partially treated meningitis

    • Glucose low: ≤40% of blood concentration highly specific for bacterial meningitis but only 80% sensitive

    • Protein elevated in almost all patients with bacterial meningitis

    • Cultures positive in 70-85% of patients

    • Likelihood of positive Gram stain result varies from 90% for Strep pneumoniae meningitis to ~30% for Listeria monocytogenes. Yield ~20% lower for patients who have received prior antibacterial therapy

    • Latex particle agglutination tests for antigen detection in CSF. Sensitivity varies with organism (from 78-100% for H. influenzae to 50-93% for N. meningitides. Negative result does not rule out bacterial meningitis and false positive results occur. Not recommended for routine use but may be indicated in patients with negative Gram stain result. May be most useful for patients who have received antibiotics prior to admission

    • Polymerase chain reaction. Use of PCR with a broad range of bacterial primers has high sensitivity and specificity for the diagnosis of bacterial meningitis. PCR for enterovirus has sensitivity of 86-100% and specificity of 92-100%. May be useful in reducing need for antibacterial therapy

    • Lactate. Measurement of CSF lactate not useful in patients with suspected community acquired meningitis. However a cutoff of 4 mmol/l had positive predictive value of 96% and negative predictive value of 94% in post-operative neurosurgical patients suspected of having bacterial meningitis

Blood cultures

  • Spread of organisms is by haematogenous route. Blood cultures should be performed in all cases (prior to the adminstration of antibiotics unless this will result in significant delay in administration)

Imaging

CT or MR scans are usually normal or mildly and non-specifically abnormal in meningitis and are not generally helpful in detecting coning. CT should be performed to exclude cerebral abscess or in patients at increased risk of herniation (see above)

C-reactive protein

  • normal CRP has high negative predictive value for bacterial meningitis

Differential diagnosis

  • Encephalitis: should be considered as the primary diagnosis in patients in whom focal signs, convulsions or disturbance of consciousness are prominent in the clinical picture
  • Aseptic meningitis: connective tissue disease, drug induced, viral or fungal meningitis

Treatment

Empirical antibiotics

Risk factor Common pathogens Recommended antibiotics
Adult 50 years N. meningitides, S. pneumoniae Vancomycin plus ceftriaxone/cefotaxime
± rifampicin if steroids given
Adult >50 years N. meningitides, S. pneumoniae, L. monocytogenes, anaerobic Gram-negative bacteria Vancomycin plus ceftriaxone/cefotaxime plus ampicillin
± rifampicin if steroids given
Base of skull fracture S. pneumoniae, H. influenzae, group A ß-haemolytic streptococci Vancomycin plus ceftriaxone/cefotaxime
Penetrating head trauma or post neurosurgery Staphylococcus aureus, coagulase -ve staphylococci, aerobic gram negative bacilli (including Ps aeruginosa) Vancomycin plus cefepime/ceftazidime/meropenem
CSF shunt Staphylococcus aureus, coagulase -ve staphylococci, aerobic gram negative bacilli (including Ps aeruginosa), Propionibacterium acnes Vancomycin plus cefepime/ceftazidime/meropenem

Click here for doses recommended by the Infectious Diseases Society of America

Antibiotics based on presumptive pathogen identification by positive Gram stain

Bacteria First line Alternatives
S. pneumoniae Vancomycin plus ceftriaxone/cefotaxime Meropenem, gatifloxacin/moxafloxacin (may be less suitable in Asia where MICs for these agents is higher)
N. meningitides Ceftriaxone/cefotaxime Penicillin G or ampicillin (should not be used in areas with penicillin resistant meningococci (eg Spain)); chloramphenicol, fluoroquinolone; aztreonam.
L. monocytogenes Ampicillin/penicillin G ±aminoglycoside Trimethoprim-sulfamethoxazole, meropenem,
H. influenzae Ceftriaxone/cefotaxime Chloramphenicol, cefepime, meropenem, fluoroquinolone
E. coli Ceftriaxone/cefotaxime Cefepime, meropenem, aztreonam, fluoroquinolone, trimethoprim-sulfamethoxazole

Click here for doses recommended by the Infectious Diseases Society of America. Fluoroquinolones should only be used for meningitis due to multidrug-resistant Gram negative bacilli or when patients have not responded or cannot receive standard antimicrobial therapy

Antibiotics based on isolated pathogen and susceptibility testing

  • Click here to link to recommendations of the Infectious Diseases Society of America
  • When vancomycin is used, aim for trough concentrations of 15-20 mg/L
  • Rifampicin should be used in combination with vancomycin for CSF shunt infections due to staphylococci if the organism is shown to be susceptible

Duration of antibiotic therapy

More based on tradition than evidence. ISDA recommend:

  • 7 days for N. meningitides or H. influenzae
  • 10-14 days for S. pneumoniae
  • 21 days for aerobic Gram negative bacilli
  • ≥21 days for L. monocytogenes

However duration of therapy should be adjusted according to patient response.

Steroids

  • rationale is that steroids may attenuate the inflammatory response in the subarachnoid space, which is a major factor contributing to morbidity and mortality
  • dexamethasone 10 mg 6 hourly IV for 4 days administered to adults with bacterial meningitis 15-20 min before first dose of antibiotics associated with decreased risk of unfavourable outcome and death (click here to read the paper). Benefit restricted to those with meningitis due to Strep. pneumoniae
  • IDSA recommendation:
    • dexamethasone 0.15 mg/kg  6 hourly for 2-4 days
    • first dose administered 10-20 min before or, at least concomitant with first dose of antibiotics
    • all adults with suspected/proven Strep. pneumoniae meningitis
    • continue only if CSF Gram stain shows Gram positive diplococci or if blood or CSF cultures are postive for Strep. pneumoniae
    • do not give dexamethasone to those patients who have already received antibiotics
  • theorectical concern that use of steroids may reduce the penetration of vancomycin into the brain and therefore worsen outcome in patients with highly penicillin-resistant or highly cephalosporin-resistant organisms. ISDA recommends continuing dexamethasone even if these organisms are isolated.

Supportive therapy

Avoid wide fluctuations in BP which may affect cerebral blood flow, avoid excessive hyperventilation and do not limit fluids. High levels of vasopressin seen in these patients is an appropriate response to hypovolaemia

Chemoprophylaxis

Should be given to close family, household and nursery contacts of patients with meningococcal and Haemophilus meningitis. Rifampicin 10 mg/kg bd ofr 2 days (meningococcal) or 20 mg/kg/day for 4 days (Haemophilus). Alternatives: ciprofloxacin (single oral dose) or ceftriaxone (single injection). NB index case also requires chemoprophylaxis prior to leaving hospital as successful treatment of meningitis does not eradicate the carrier state.

Complications

  • DIC: meningococcal
  • Hydrocephalus
  • Deafness: pneumococcal > meningococcal/Haemophilus
  • mild to debilitating neurological impairment

Further reading

IDSA practice guidelines for the management of bacterial meningitis


© Charles Gomersall December 1999, December 2004

 

©Charles Gomersall, April, 2014 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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