The levels of evidence (class I-IV) supporting the recommendations and ratings of recommendations (A-C, Good Practice Points) are defined at the end of the "Major Recommendations" field.
Early Management of Acute Bacterial Meningitis (ABM)
- The Task Force recommends (see the flow chart in the original guideline document) that all patients with suspected ABM should be hospitalized as soon as possible [IIIA]. Care of patients with suspected ABM should be considered as an emergency and fast-tracked for rapid assessment and treatment. The following timeline for management of ABM is proposed: admission to hospital within first 90 minutes (min) of making contact with health service; and assessment and treatment commenced within 60 min of hospital admission, and no longer than 3 hours (h) after contact with health service [IVC].
- Pre-hospital antibiotic treatment should only be initiated for patients with strong suspicion of disseminated meningococcal infection (meningococcemia) because of the unpredictable risk of early circulatory collapse from adrenocortical necrosis (Waterhouse–Friderichsen syndrome). For other patients, rapid preadmission antibiotic therapy should be considered only if a delay in excess of 90 min in hospital transfer is anticipated [IIIC].
- Lumbar puncture (LP) and cerebrospinal fluid (CSF) analysis is the specific investigation required for diagnosis and management of ABM. Therefore, if diagnosis of bacterial meningitis is suspected and there are no clinical contraindications, LP should be performed as soon as safely possible [IIIC].
- In patients with symptoms and signs suggestive of raised intracranial pressure or with high risk of cerebral herniations following LP (imaging evidence of intracranial mass lesion, obstructive hydrocephalus or midline shift), diagnostic LP should be postponed [IA].
- In a patient with suspected ABM in whom LP is being delayed or postponed, antibiotic therapy should be commenced immediately after collecting blood sample for culture. Intravenous (IV) or intramuscular (IM) Benzyl Penicillin, or IV Cefotaxime or Ceftriaxone should be administered as empirical therapy for ABM and may be commenced immediately [IIIA].
- In patients with known history of severe beta-lactam allergy, vancomycin should be administered as the alternative for pneumococcal meningitis and chloramphenicol for meningococcal meningitis [IVC].
- In regions with known or suspected penicillin-resistant strains of pneumococcus, high dose vancomycin should be used in combination with a third-generation cephalosporin [IVC].
- Patients with risk factors for Listerial meningitis (old age, immunosuppressed and/or signs of rhombencephalitis) should receive IV amoxicillin in addition to a third-generation cephalosporin as the empirical treatment of ABM initially [IVC].
- Dexamethasone in high doses may be appropriate as an adjunctive therapy and should be given shortly before or with the first dose of antibiotics (see Adjunctive Therapy on ABM below).
- All ABM patients should be managed as medical emergencies and when available, treated in neurological intensive care units.
Specific Antibiotic Treatment
- Initial antibiotic treatment of ABM should be parenteral [IA].
Empirical Antibiotic Therapy in Suspected ABM
Ceftriaxone 2 g 12 to 24 hourly or Cefotaxime 2 g 6 to 8 hourly [IIIB]
Alternative therapy: Meropenem 2 g 8 hourly [IIIC] or Chloramphenicol 1 g 6 hourly.
If penicillin or cephalosporin-resistant pneumococcus is suspected, use Ceftriaxone or Cefotaxime plus Vancomycin 60 mg/kg/24 hourly (adjusted for creatinine clearance) after loading dose of 15 mg/kg [IVA].
Ampicillin/Amoxicillin 2 g 4 hourly if Listeria is suspected [IVA].
Pathogen Specific Therapy
- Penicillin-sensitive Pneumococcal meningitis (and including other sensitive Streptococcal species): Benzyl Penicillin 250,000 Units/kg/day (equivalent to 2.4 g 4 hourly) [IVA] or Ampicillin/Amoxicillin 2 g 4 hourly or Ceftriaxone 2 g 12 hourly or Cefotaxime 2 g 6 to 8 hourly. Alternative therapy: Meropenem 2 g 8 hourly [IVC] or Vancomycin 60 mg/kg 24 hourly as continuous infusion (adjusted for creatinine clearance) after 15 mg/kg loading dose aiming for serum levels of 15 to 25 mg/l) plus Rifampicin 600 mg 12 hourly [IVC] or, Moxifloxacin 400 mg daily [IVC]
- Pneumococcus with reduced susceptibility to penicillin or cephalosporins: Ceftriaxone or Cefotaxime plus Vancomycin ± Rifampicin [IV]. Alternative therapy: Moxifloxacin, Meropenem or Linezolid 600 mg combined with Rifampicin [IV]
- Meningococcal meningitis: Benzyl Penicillin or Ceftriaxone or Cefotaxime [IV]. Alternative therapy: Meropenem or Chloramphenicol or Moxifloxacin [IVC]
- Haemophilus influenzae type B (Hib): Ceftriaxone or Cefotaxime [IVC]. Alternative therapy: IV Chloramphenicol–Ampicillin/ Amoxicillin [IVC]
- Listerial meningitis: Ampicillin or Amoxicillin 2 g 4 hourly ± Gentamicin 1 to 2 mg 8 hourly for the first 7 to 10 days [IVC]. Alternative therapy: Trimethoprim–Sulfamethoxazole 10 to 20 mg/kg 6 to 12 hourly or Meropenem [IV]
- Staphylococcal species: Flucloxacillin 2 g 4 hourly [IV] or Vancomycin if penicillin allergy is suspected [IV]. Rifampicin should also be considered in addition to either agent, and Linezolid for methicillin-resistant staphylococcal meningitis [IVC].
- Gram-negative Enterobacteriaceae: Ceftriaxone or Cefotaxime or Meropenem
- Pseudomonal meningitis: Meropenem ± Gentamicin
Duration of Therapy
- Unspecified bacterial meningitis: 10 to 14 days [IVC]
- Pneumococcal meningitis: 10 to 14 days [IVA]
- Meningococcal meningitis: 5 to 7 days [IVA]
- Hib meningitis: 7 to 14 days [IVB]
- Listerial meningitis: 21 days [IVB]
- Gram-negative bacillary and Pseudomonal meningitis: 21 to 28 days [IVB]
Adjunctive Therapy of ABM
- Adjuvant dexamethasone is recommended with or shortly before the first parenteral dose of antibiotic in all previously well and non-immunosuppressed adults with pneumococcal meningitis at a dose of 10 mg every 6 hours for 4 days [IA] and children at a dose of 0.15 mg/kg every 6 hours for 4 days for Hib and pneumococcal meningitis [IA].
- In all patients with clinically suspected pneumococcal (or Hib) meningitis (early focal neurological signs), the Task Force recommends that dexamethasone is given with the first dose of empirical antibiotic therapy as above [IVC].
- In ABM because of other bacterial aetiology, routine use of high dose dexamethasone is not presently recommended [IA].
- If dexamethasone was initiated on clinical suspicion of ABM, which was subsequently proven to be inaccurate by CSF microbiology, the treatment should be promptly withdrawn.
- There is insufficient evidence to recommend the use of dexamethasone in pharmacological doses after antibiotic therapy has begun. Dose and duration of therapy with corticosteroids in such cases should be guided by specific clinical indications in individual patients (e.g., physiological doses of steroids in cases of adrenal insufficiency because of meningococcemia, pharmacological doses of steroids for raised intracranial pressure).
- By reducing subarachnoid space inflammation and blood brain barrier permeability, steroids may lower CSF penetration of antibiotics and patients receiving vancomycin for penicillin-resistant pneumococcal meningitis require close clinical and CSF monitoring.
Other Symptomatic and Adjunctive Therapies
Circulatory shock as part of severe sepsis or in meningococcemia should be handled in neurointensive care unit. Treatment should consist of a 30 degree head-up position, head midline, minimal suction, deep sedation, normo- or moderate hypothermia and strict avoidance of hypercapnia (Nadel and Kroll, 2007). Head elevation and hyperosmolar agents are recommended for the management of cerebral oedema but have never been systematically evaluated in the context of bacterial meningitis. As a hyperosmolar agent, 20% mannitol may be given intravenously either as a bolus injection of 1 g/kg over 10 to 15 min, repeated at 4 to 6 hour intervals, or in smaller but frequent doses (0.25 mg/kg every 2 to 3 hours), to maintain a target serum osmolality of 315 to 320 mOsm/l [IVC]. CSF pressure monitoring may be helpful in cases where CSF drainage (ventricular) is under consideration for obstructive hydrocephalus, and the decision to perform the procedure should be based on patient's level of consciousness and the degree of ventricular dilatation visualized in brain imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) [IVC]. Seizures are frequent in ABM and are associated with severe inflammation, structural brain lesion and pneumococcal meningitis may increase mortality (Zoons et al., 2008) and should be treated with a parenteral anticonvulsant, such as phenytoin (fosphenytoin) [IIIB]. Prophylactic anticoagulation to prevent deep vein thrombosis may be considered in patients who do not have coagulopathy and are considered to be at a high risk of deep vein thrombosis (e.g., obesity and recent hip surgery). Heparin was considered beneficial in a retrospective study of patients with septic cavernous sinus thrombosis; however, experience with therapeutic anticoagulation for venous sinus thrombosis in ABM is limited and is best reserved for patients who deteriorate neurologically because of venous sinus thrombosis and require close monitoring of coagulation profile and brain imaging [IVC].
Managing Complications of ABM
- All survivors of ABM should be offered access to neurology service
- Audiometry is recommended in recovering patients with suspected hearing impairment.
- Seizures in patients with ABM may be early (acute symptomatic epilepsy) or delayed, appearing after several months or years. Long-term antiepileptic drug therapy is recommended in patients with late-onset seizures. For patients with acute symptomatic seizures, antiepileptic drug therapy may be withdrawn after 1 year, in the absence of seizure recurrence and structural brain (cortical) injury as visualized in brain imaging.
- Driving restriction in adults may apply if they had seizures, or have functional impairment such as visual field defect and limb weakness.
Prevention of Secondary Cases of ABM
- All cases of suspected meningococcal or Hib meningitis should be reported urgently to the local public health authorities [IVC].
- Chemoprophylaxis with either oral rifampicin (600 mg 12 hourly for 48 hours), ciprofloxacin (500 mg single dose) or ceftriaxone (IV or IM injection of a single 1 g dose) should be given to those adults with meningococcal infection who were treated without a third-generation cephalosporin [IVC].
- Chemoprophylaxis with either rifampicin, ciprofloxacin or ceftriaxone should be given to household or close contacts of patients with suspected or proven meningococcal or Haemophilus infection [IVC].
- A therapeutic 7-day course of phenoxymethyl penicillin or amoxicillin should be considered in addition to chemoprophylaxis for any household or close contact of a patient with meningococcal disease aged <15 years [IVC].
- Chemoprophylaxis for meningococcal meningitis is rarely indicated for health-care workers and is only recommended in situations where there has been mouth to mouth contact or direct exposure to infectious droplets from a patient with meningococcal disease [IVC].
- Immunization with Meningococcal or H. influenzae type B vaccine should be considered in the public health management of an outbreak [IVC].
- Primary vaccination against N. meningitidis and H. influenzae type B infection should be given to all at risk groups [IVC].
- Vaccination against N. meningitides type C and H. influenzae type B should be given to all children as part of the normal childhood immunization schedule [IVC].
Evidence Classification Scheme for a Diagnostic Measure
Class I: A prospective study in a broad spectrum of persons with the suspected condition, using a "gold standard" for case definition, where the test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy
Class II: A prospective study of a narrow spectrum of persons with the suspected condition, or a well-designed retrospective study of a broad spectrum of persons with an established condition (by "gold standard") compared to a broad spectrum of controls, where test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy
Class III: Evidence provided by a retrospective study where either persons with the established condition or controls are of a narrow spectrum, and where test is applied in a blinded evaluation
Class IV: Any design where test is not applied in blinded evaluation OR evidence provided by expert opinion alone or in descriptive case series (without controls)
Evidence Classification Scheme for a Therapeutic Intervention
Class I: An adequately powered prospective, randomized, controlled clinical trial with masked outcome assessment in a representative population or an adequately powered systematic review of prospective randomized controlled clinical trials with masked outcome assessment in representative populations. The following are required:
- Randomization concealment
- Primary outcome(s) is/are clearly defined
- Exclusion/inclusion criteria are clearly defined
- Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias
- Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences
Class II: Prospective matched-group cohort study in a representative population with masked outcome assessment that meets a–e above or a randomized, controlled trial in a representative population that lacks one criteria a–e
Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment
Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion
Rating of Recommendations for a Diagnostic Measure
Level A rating (established as useful/predictive or not useful/predictive) requires at least one convincing class I study or at least two consistent, convincing class II studies.
Level B rating (established as probably useful/predictive or not useful/predictive) requires at least one convincing class II study or overwhelming class III evidence.
Level C rating (established as possibly useful/predictive or not useful/predictive) requires at least two convincing class III studies.
Rating of Recommendations for a Therapeutic Intervention
Level A rating (established as effective, ineffective, or harmful) requires at least one convincing class I study or at least two consistent, convincing class II studies.
Level B rating (probably effective, ineffective, or harmful) requires at least one convincing class II study or overwhelming class III evidence.
Level C rating (possibly effective, ineffective, or harmful) requires at least two convincing class III studies.
Good Practice Points Where there was a lack of evidence but consensus was clear, the Task Force has stated their opinion as good practice points.