Approach

Bacterial meningitis may prove fatal within hours. Patients with suspected acute bacterial meningitis should be rapidly admitted to the hospital and assessed to determine whether a lumbar puncture (LP) is clinically safe.

Antimicrobials should be given promptly. If the LP is delayed because a computed tomography scan is needed, antibiotic treatment should be started before the scan and after blood samples have been obtained for culture. Delaying antibiotics is strongly associated with poor outcome and death.[59]​​[101][102]​​ A multinational, retrospective cohort study showed that waiting to give antibiotics for more than 2 hours significantly increased the mortality in patients with community-acquired bacterial meningitis.[103]​ When the specific organism is identified and results of susceptibilities are known, treatment can be modified accordingly.

The following recommendations are for community-acquired meningitis. Recommendations for the management of healthcare-associated meningitis are beyond the scope of this topic, and guidelines are available elsewhere.[99] See Meningococcal disease.

Suspected bacterial meningitis

Empiric parenteral broad-spectrum antibacterial therapy should be given as soon as possible for suspected bacterial meningitis (preferably after an LP has been performed).[9][99][103]​​[104]​​[105]​​​​​ In some countries, administration of antibiotics (e.g., intramuscular penicillin-G, cefotaxime, or ceftriaxone) in primary care is recommended if transfer to the hospital is likely to be delayed.​​[57]​ However, the evidence for this approach is equivocal.[106]

The choice of empiric antibiotic depends on the patient's age and the conditions that may have predisposed the patient to meningitis.[6][107]​​ The regimen chosen must be broad enough to cover the potential organisms for the age group affected, with consideration for regional susceptibility rates.[59]

Most empiric therapy regimens include a third generation cephalosporin plus vancomycin. Ampicillin is added in situations where Listeria monocytogenes may be a pathogen (e.g., age >50 years, immunocompromised, and newborns).[1] Trimethoprim/sulfamethoxazole is an alternative to ampicillin (excluding newborns) in Listeria patients.[107][108]

A proposed treatment strategy based on age and specific predisposing conditions follows.[1][59]​​​[104][107]

  • Age ≤1 month immunocompetent: ampicillin plus cefotaxime. If a cephalosporin cannot be administered (e.g., patients with an allergy), an alternative regimen is ampicillin plus an aminoglycoside (e.g., gentamicin)

  • Age >1 month and <50 years immunocompetent: cefotaxime or ceftriaxone plus vancomycin. If a cephalosporin cannot be administered (e.g., patients with an allergy), a carbapenem (e.g., meropenem) plus vancomycin can be considered

  • Age ≥50 years or immunocompromised (any age): ampicillin plus cefotaxime or ceftriaxone plus vancomycin. If ampicillin cannot be administered (e.g., patients with an allergy) trimethoprim/sulfamethoxazole could be considered as an alternative in place of ampicillin (excluding newborns where specialist advice should be sought).

Adjunctive corticosteroid

The general recommendation is for dexamethasone to be given to all patients older than 6 weeks who present with clinical features of bacterial meningitis.[6][64]​​[104]​​[109][110]

​Dexamethasone reduces inflammation in the cerebrospinal fluid (CSF), which is amplified by bacteriolytic antibiotics. The timing of starting corticosteroids varies. In the US, the Infectious Diseases Society of America recommends that dexamethasone be started immediately prior to, or in conjunction with, the first dose of antibiotics and continuing for 2-4 days or until the specific organism has been identified.[6][108]​​​​ European and UK guidelines recommend starting dexamethasone shortly before or in conjunction with antibiotics, or within 4-12 hours if already commenced.[64][108]​​

Once the causative organism is isolated, the use of dexamethasone should be reviewed; guidelines recommend that it is only continued for bacterial meningitis caused by pneumococcus or Haemophilus influenzae type b (Hib) as these have the strongest evidence for benefit.[107][108]​​​​[111]

Evidence suggests that there is benefit from high-dose dexamethasone in reducing mortality and hearing impairment in adults with bacterial meningitis.[111] One observational study of 1391 adults with community-acquired bacterial meningitis also showed that the proportion of patients with unfavorable outcomes was lower in individuals treated with adjunctive dexamethasone in patients with nonpneumococcal and non-Haemophilus meningitis (with the exception of Listeria).[112]

In children, studies have shown corticosteroids likely reduce severe hearing loss in patients with Hib meningitis, but not necessarily in children with meningitis due to non-Haemophilus species.[113] In one meta-analysis of clinical studies published during 1988-1996, adjunctive dexamethasone had confirmed benefit for Hib meningitis and, if commenced with or before antimicrobial therapy, suggested benefit for pneumococcal meningitis in children.[114]

One more recent large meta-analysis found administration of low-dose corticosteroids to be beneficial in children in reducing hearing loss and neurologic sequelae, as well as reducing the mean number of days before resolution of fever.[115] There is low-quality evidence to suggest dexamethasone may reduce death and hearing loss in neonates with bacterial meningitis.[116] Corticosteroids are, however, not currently recommended in neonates.[59]

Dexamethasone generally should not be withheld in immunocompromised patients. In studies where it has been given to patients with bacterial meningitis, including those with Listeria, mortality tended to be lower in those on adjunctive dexamethasone therapy as compared to those without dexamethasone therapy.[108][110]​​

The use of adjunctive dexamethasone in Listeria meningitis is controversial. In a prospective French cohort study of patients with neurolisteriosis, the use of corticosteroids was associated with increased mortality, while a Dutch prospective study showed a reduction in mortality, showing more studies are needed.[117][118]​​ It is advised to consult an infectious disease specialist.

Supportive therapy

The major goal of supportive therapy is to restore and maintain normal respiratory, cardiac, and neurologic function. Meningococcal infections may progress rapidly and clinical deterioration may continue despite prompt administration of antimicrobial therapy.

Initial assessment should follow the principles of pediatric and adult advanced life support, by evaluating the patient's airway, breathing, and circulatory status, and establishing secure, large-caliber intravenous catheters for giving fluids.[119][120]

Patients with symptoms of compensated shock (neurologic status usually remains normal, but the pulse rate may be persistently elevated, the skin mottled, the extremities cool due to increased systemic vascular resistance, the capillary refilling prolonged, and the urinary output decreased) or respiratory distress should receive supplemental oxygen. Those with decompensated shock (signs of compensated shock plus hypotension), hypoxia, severe respiratory distress, altered consciousness, or evidence of elevated intracranial pressure require intubation and mechanical ventilation.

Adequate oxygenation, prevention of hypoglycemia and hyponatremia, anticonvulsant therapy to control and prevent seizures, and measures to decrease intracranial pressure and to prevent fluctuating cerebral blood flow are important in managing patients with bacterial meningitis.[9]​ Vasopressors should be given to patients with hypotension or poor perfusion who do not respond promptly to fluid resuscitation. Consult a specialist for guidance on suitable vasopressor/inotrope regimens. If the patient is hypovolemic or in shock (state of reduced end-organ oxygenation caused by an imbalance between tissue oxygen delivery and demand resulting in an oxygen debt), additional intravenous fluids must be given. One systematic review found insufficient evidence to guide practice on whether maintenance or restricted fluid regimens should be used.[121] However, fluids should be given cautiously to patients with evidence of elevated intracranial pressure, myocardial dysfunction, or acute respiratory distress syndrome.

Central venous catheter insertion: animated demonstration
Central venous catheter insertion: animated demonstration

Ultrasound-guided insertion of a non-tunnelled central venous catheter (CVC) into the right internal jugular vein using the Seldinger insertion technique.

Peripheral intravascular catheter: animated demonstration
Peripheral intravascular catheter: animated demonstration

How to insert a peripheral intravascular catheter into the dorsum of the hand.

​​
Tracheal intubation: animated demonstration
Tracheal intubation: animated demonstration
Bag-valve-mask ventilation: animated demonstration
Bag-valve-mask ventilation: animated demonstration

How to use bag-valve-mask apparatus to deliver ventilatory support to adults. Video demonstrates the two-person technique.

​​​

Confirmed bacterial meningitis

After the diagnosis has been confirmed (generally within 12-48 hours of admission to the hospital), the patient's antibacterial therapy can be modified according to the causative organism and its susceptibilities.[9][107]​​

Typically, the duration of antibacterial treatment depends on the clinical response and the CSF microbiologic response after treatment has started. A recent meta-analysis looking at shorter (up to 7 days) versus longer (10 days or double the short course) treatment in children found no difference in regard to treatment failure, relapse, mortality, neurologic complications, and/or hearing impairment at discharge and at follow-up.[136]

Supportive therapy, such as fluid replacement, should be continued.

S pneumoniae (duration of therapy 10-14 days)[107]

  • Penicillin-susceptible (minimum inhibitory concentration [MIC] ≤0.06 microgram/mL): ampicillin or penicillin-G. Alternatives include a third-generation cephalosporin (e.g., ceftriaxone). Penicillin-intermediate (MIC=≥0.12 microgram/mL) or ceftriaxone-intermediate (MIC <1 microgram/mL): cefotaxime or ceftriaxone. Alternatives include a carbapenem (e.g., meropenem) or a fourth-generation cephalosporin (e.g., cefepime). Penicillin-resistant (MIC ≥2.0 micrograms/mL) or cephalosporin-resistant (MIC ≥1.0 microgram/mL): vancomycin plus cefotaxime or ceftriaxone. Alternatives include vancomycin plus a fluoroquinolone.​ Alternatives include vancomycin plus a fluoroquinolone.​​​[107][108]​​​​​[137]​​

H influenzae (duration of therapy 7-10 days)[107]

  • Beta-lactamase-negative: ampicillin. Alternatives include a third- or fourth-generation cephalosporin (e.g., ceftriaxone, cefepime) or a fluoroquinolone.

  • Beta-lactamase-positive: cefotaxime or ceftriaxone. Alternatives include a fourth-generation cephalosporin (e.g., cefepime) or a fluoroquinolone.

Streptococcus agalactiae (group B streptococci) (duration of therapy 14-21 days)[107]

  • Ampicillin or penicillin-G. Alternatives include a third-generation cephalosporin (e.g., ceftriaxone, cefotaxime) or vancomycin.

Escherichia coli and other gram-negative Enterobacteriaceae (duration of therapy 21-28 days)[107][108]

  • Ceftriaxone or cefotaxime. Alternatives include aztreonam, a fluoroquinolone, trimethoprim/sulfamethoxazole, meropenem, or ampicillin.

Listeria monocytogenes (duration of therapy 21-28 days)[107][108]

  • Gentamicin plus ampicillin or penicillin-G. Alternatives include trimethoprim/sulfamethoxazole.

Staphylococcus aureus (duration of therapy depends on microbiologic response of CSF and underlying illness of the patient)[107][108]

  • Methicillin-susceptible: nafcillin or oxacillin. Alternatives include vancomycin, linezolid, or daptomycin. Methicillin-resistant: vancomycin. Alternatives include trimethoprim/sulfamethoxazole, linezolid, or daptomycin.

Staphylococcus epidermidis (duration of therapy depends on microbiologic response of CSF and underlying illness of the patient)[108][138]

  • Vancomycin. Alternatives include linezolid.

Pseudomonas aeruginosa (duration of therapy 21 days)[108][139][140]​​

  • Ceftazidime. Alternatives include meropenem.

Enterococcus species (duration of therapy 21 days)[99][108]​​[141][142]

  • Ampicillin plus gentamicin. Alternatives include vancomycin plus gentamicin (if ampicillin resistant), or linezolid (if ampicillin and vancomycin resistant)

Acinetobacter species (duration of therapy 21 days)[143]

  • Meropenem with or without gentamicin. An alternative regimen (in cases of resistance) includes intraventricular polymyxin B (given intrathecally) plus an aminoglycoside with or without rifampin.

N meningitides (duration of therapy 7 days)​[59][107][108]

  • Penicillin-susceptible (MIC <0.1 microgram/mL): ampicillin or penicillin-G. Alternatives include a third-generation cephalosporin (e.g., ceftriaxone). Penicillin-intermediate (MIC=0.1 to 1.0 microgram/mL): cefotaxime or ceftriaxone. Alternatives include a fluoroquinolone or meropenem.

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[144]

  • Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability).

  • Consult your local guidelines and drug information source for more information on suitability, contraindications, and precautions.

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