EBM Meningitis

Pedagogical disambiguation: Emergency Medicine Lecture Notes and Evidence Based emergency medicine principles from Professor A.F.T Brown and the Life in the Fast Lane team.

Adult Bacterial Meningitis

Typical Presentations

• Fever (75-85%), headache (87%), objective neck stiffness or meningismus (70-83%), signs of cerebral dysfunction such as confusion (69%), delirium or declining consciousness.
• Triad of fever, neck stiffness and altered mental status in 44%; but at least two of possible tetrad of headache, fever, neck stiffness and altered mental status occur in 95%.
• Vomiting (35%), seizures (15-30%), cranial nerve palsies or focal neurological signs (23-33%), Kernig’s (9%) or Brudzinski’s signs of meningismus, papilloedema (1%).
• Jolt accentuation of headache (100% – see Attia paper) !

Newman D. Clinical assessment of meningitis in adults. Ann Emerg Med 2004; 44: 71-3. [Reference]

Attia J, Hatala R, Cook DJ et al.  Does this adult patient have acute meningitis? JAMA 1999; 282:175-81. [Reference] (NB The authors’ suggestion in this meta-analysis that absence of jolt accentuation of headache in patients with fever essentially excludes meningitis is flawed, as was based on one 1991 Japanese paper, which had just one actual meningitis case studied!)

Atypical presentations

• Elderly: lethargy, obtundation, absence of fever and minimal signs meningismus.
• Neutropenia / immunocompromise: subtle signs due to impaired ability to mount inflammatory response.
• Neonates, infants and young children: poor feeding, irritability, N&V, fever

“a sick looking child with fever has bacterial meningitis / menigococcaemia until proven otherwise.”

Diagnosis

• 10% lymphocyte predominance in CSF, usually infants with gram negative infection, or in Listeria meningitis.
• 60-90% positive CSF on gram stain. Drops to 40-60% if prior antibiotics, with blood cultures rarely positive after treatment.
• Polymerase chain reaction (PCR) amplification of DNA in blood or CSF ie. N.meningitidis and viruses + new generation pneumococcal antigen testing on CSF.

Management

• CT is performed before LP, in order to exclude alternate mass lesion diagnoses such as cerebral abscess, subdural empyema or toxoplasma encephalitis, particularly in presence of focal neurology and fluctuating or reduced  conscious level.
  • a normal scan does not exclude raised ICP (see below).
• Lumbar puncture is contraindicated irrespective of CT findings in shock, widespread rash or evidence of coagulopathy, drowsiness / impaired consciousness, signs of raised ICP (bradycardia, hypertension, papilloedema, periodic breathing), and with focal neurology.

Straus S, Thorpe K, Holroyd-Leduc J. How do I perform a lumbar puncture and analyse the results to diagnose bacterial meningitis? JAMA 2006 ;296 :2012-22. [Reference]

Clark T, Duffell E, Stuart J et al. Lumbar puncture in the management of adults with suspected bacterial meningitis – a survey of practice. J Infection 2006 ;52 :315-19. [Reference]

• Immediate antibiotic therapy is paramount.
  • Ceftriaxone 4 g (child 100 mg/kg up to 4 g) IV daily or 2 g (50 mg/kg up to 2 g)  IV 12-hrly
  • - ADD benzyl penicillin 2.4 g (child 60 mg/kg up to 2.4 g) IV 4-hrly if immunocompromised and Listeria monocytogenes is possible (adults over 50 yr, alcohol abuse, pregnant).
  • - ADD vancomycin 1.5 g IV 12-hrly if Strep. pneumoniae on CSF antigen or otitis media / sinusitis. Or if Staph. aureus is suspected, or neutrophils in CSF but no organisms seen (and if viral meningitis / meningococcal disease are unlikely).

Therapeutic Guidelines Ltd. Therapeutic Guidelines. Antibiotic; Version 14, 2010. [Reference]

• Steroids
  • Use now challenged again! Lancet Neurol meta-analysis showed no statistically significant reduction in death or neurological disability, even in the 15 pre-specified study subgroups. Only effect was on      reduction in hearing loss (OR 0.77). Although no harm shown either, routine use not supported
  • Usual dose was dexamethasone 10 mg IV 6-hrly (0.15 mg/kg) before or with first  dose of antibiotic then 6-hrly for 4 days.

van de Beek D, Farrar J, de Gans J et al. Adjunctive dexamethasone in bacterial meningitis : a meta-analysis of individual patient  data. Lancet Neurol 2010 ;9 :254-63. [Reference]

Vardakas K, Matthaiou D, Falagas M. Adjunctive dexamethasone therapy for bacterial meningitis in adults : a meta-analysis of randomised controlled trials. Europ J Neurol 2009 ;16 :662-73. [Reference]

van de Beek D, de Gans J, Spanjaard L et al. Clinical features and prognostic factors in adults with bacterial meningitis. N Eng J Med 2004; 351:1849-59. [Reference]

Heyderman R, Lambert H, O’Sullivan I et al. Early management of suspected bacterial meningitis and meningococcal septicaemia in adults. J Infection 2003; 46: 75-7 [PDF Reference]. (Editorial: Cohen J. Management of bacterial meningitis in adults. BMJ 2003; 326: 996-7.) [Reference]

Beaman M, Wesselingh S. Acute community-acquired meningitis and encephalitis. MJA 2002; 176:389-396. [Reference]

Meningococcal Disease – “Meningococcaemia”

Epidemiology:

• Potentially pathogenic meningococci present in 2-10% asymptomatic carriers.  Droplet / oropharyngeal secretion spread (viability in air only a few seconds).
• Developed-world: disease predominantly serogroups B, C, Y, W135 (in Australia 62% is B, 32% C but over 60% deaths are group C).
• Developing-world: predominantly serogroup A.
• Increased risk in smokers, recent illness, crowded conditions and multiple kissing partners + functional or actual asplenia.
• Overall case fatality rate 5.6% in UK.

Clinical syndromes include:

• ‘Early’ signs (median of 8 hrs) include leg pains, cold hands and feet, and abnormal skin colour such as pallor or mottling in 72% children.

Thompson M, Ninis N, Perera R et al. Clinical recognition of meningococcal disease in children and adolescents. Lancet 2006; 367:397-403. [Reference] (Editorial: Nascimento-Carvalho CM, Moreno-Carvalho O. Lancet 2006; 367:371-2) [Reference].

• Or may be fulminant with rapidly spreading purpura, impaired consciousness and vascular collapse plus coagulopathy with DIC (15-20%) by median of 13-22 hrs. Note rash may be blanching macular or maculopapular in first 24 hours.
• Invasion of meninges (80-85%), purulent leptomeninges, encephalitis, or other organs affected such as heart, joints, eyes (uncommon).
• Chronic meningococcaemia (rare).
• Transient bacteraemia with no sequelae.
• Note that meningitis is not a prerequisite to diagnose meningococcaemia. Also that one useful early differentiating feature for influenza is the presence of a cough; therefore if a cough is absent, do not diagnose “the ‘flu” in a sick person with fever and myalgia etc.

Management

• Immediate benzyl penicillin 1.2 g IV or IM prehospital for suspected meningococcaemia (rigors, fever plus rash)/ meningococcal meningitis.
• Ceftriaxone 4 g (child 100 mg/kg up to 4 g) IV daily or 2 g (50 mg/kg up to 2 g) IV 12-hrly, plus benzyl penicillin 2.4 g (child 60 mg/kg up to 2.4 g) IV 4-hrly until sensitivities known, immediately on suspicion meningococcaemia / bacterial meningitis in hospital, after blood cultures (do not await LP if sick).
• Correction hypovolaemia – may require large volumes of fluids (20 mL/kg repeated x 3 early) then with catecholamine vasopressors / inotropes to optimise cardiac function.
• IPPV for altered mental state, raising ICP, hypoventilation, hypoxia and pulmonary oedema.
• Treatment of DIC, immunomodulation (experimental), surgery including fasciotomy, debridement, amputation, grafting.

Chemoprophylaxis (meningococcal meningitis or meningococcaemia):

• Close household contacts or kissing contacts, give rifampicin 600 mg orally bd for 2 days, or ceftriaxone 250 g IM once (if pregnant / liver disease), or ciprofloxacin 500 mg orally once (women on OCP).
• Vaccine – conjugate against group C, and possibly now A (both long term protection) for non-immunised contacts, or tetravalent polysaccharide against groups A, C, W135, Y; except if known outbreak of serogroup B. http://www.immunise.health.gov.au

National Institute for Health and Clinical Excellence. Bacterial meningitis and meningococcal septicaemia… in children and young people younger than 16 years in primary and secondary care. Jun / Sept 2010.  [PDF Reference]

Baumer J. Guideline review: management of invasive meningococcal disease, SIGN. Arch Dis Child Educ Pract Ed 2009;94:46-49 [Reference]

Hart C, Thomson A. Meningococcal disease and its management in children. BMJ 2006;333:685-90. [Reference]

Yung A, McDonald M. Early clues to meningococcaemia. MJA 2003; 178: 134-7. [Reference]