What are the current treatment recommendations for acute pyogenic (bacterial) meningitis, including empiric intravenous antimicrobial regimens and adjunctive dexamethasone for adults and children?

Current Treatment Recommendations for Acute Pyogenic Meningitis

Initiate empiric intravenous antimicrobial therapy immediately upon suspicion of bacterial meningitis, combined with adjunctive dexamethasone administered 10-20 minutes before or simultaneously with the first antibiotic dose. 1, 2

Empiric Antimicrobial Therapy

Initial Regimen Selection

• Adults and children: Start vancomycin plus a third-generation cephalosporin (ceftriaxone or cefotaxime) as the empiric regimen for suspected bacterial meningitis 1
• Vancomycin should never be used as monotherapy, even for highly resistant pneumococcal strains; always combine with a third-generation cephalosporin 1
• Maintain serum vancomycin trough concentrations of approximately 15-20 mg/mL during treatment 1
• Consider adding rifampin to the vancomycin plus cephalosporin combination in patients receiving adjunctive dexamethasone for suspected pneumococcal meningitis, as dexamethasone may reduce vancomycin CSF penetration 1, 2

Timing of Antibiotic Administration

• Bacterial meningitis is a neurologic emergency—administer antimicrobials as soon as the diagnosis is suspected, immediately after obtaining blood cultures 1, 3
• Do not delay antibiotics for imaging studies or lumbar puncture in patients with clinical signs of bacterial meningitis 1, 4
• Early administration reduces mortality and improves neurologic outcomes, particularly when given before the patient's Glasgow Coma Scale deteriorates below 10 1

Adjunctive Dexamethasone Therapy

Dosing Regimens

• Adults: Dexamethasone 10 mg IV every 6 hours for 4 days (total 40 mg/day) 1, 2, 5
• Children: Dexamethasone 0.15 mg/kg IV every 6 hours for 2-4 days 1, 2, 6
  • Use 4-day course for pneumococcal meningitis 2, 7
  • Use 2-day course for Haemophilus influenzae type b and meningococcal meningitis 2, 7
• Neonates: Dexamethasone is not recommended due to insufficient evidence of benefit 2

Critical Timing Considerations

• Optimal timing: Administer dexamethasone 10-20 minutes before or simultaneously with the first antibiotic dose to prevent the inflammatory cascade triggered by antibiotic-induced bacterial lysis 1, 2, 8
• If antibiotics already started: Dexamethasone may still be initiated up to 4 hours after the first antibiotic dose (some guidelines accept up to 12 hours), though benefit decreases with delay 2, 8, 5
• Never delay antibiotics to give dexamethasone first—both should be administered as close together as possible 8

Pathogen-Specific Recommendations

Continue dexamethasone for:

• Pneumococcal meningitis in adults: Strong evidence shows reduction in unfavorable outcomes from 52% to 26% and mortality from 34% to 14% 1, 2
• Pneumococcal meningitis in children: Consider continuation after evaluating benefits and risks 2
• Haemophilus influenzae type b meningitis in children: Strong evidence shows reduction in hearing loss (odds ratio 0.31) 2, 6

Discontinue dexamethasone if:

• Bacterial meningitis is ruled out entirely 2, 5
• Listeria monocytogenes is confirmed 2
• Other bacterial pathogens (not S. pneumoniae or H. influenzae) are identified 2, 5
• Meningococcal meningitis: No demonstrated benefit in mortality or hearing loss; routine continuation is not supported, though some clinicians may choose to continue 2

Evidence of Benefit

• In adults with bacterial meningitis, dexamethasone reduces unfavorable outcomes from 25% to 15% and mortality from 15% to 7% 1, 2, 9
• Dexamethasone reduces hearing loss (odds ratio 0.76) and neurological sequelae across all bacterial meningitis types 2
• The benefit is most pronounced in patients with moderate-to-severe disease on the Glasgow Coma Scale 1

Critical Care Management

Indications for ICU Transfer

• Transfer immediately to critical care for: 1
  • Rapidly evolving rash
  • Glasgow Coma Scale ≤12 or drop of >2 points
  • Cardiovascular instability or severe sepsis
  • Uncontrolled seizures
  • Respiratory compromise or hypoxia
  • Evidence of limb ischemia

Hemodynamic Management

• Maintain euvolemia with crystalloids as initial fluid of choice 1
• Target mean arterial pressure (MAP) ≥65 mmHg, though individualize based on age and cerebral edema presence 1
• Use norepinephrine as first-line vasopressor after euvolemia is restored 1
• Consider albumin for persistent hypotensive shock despite corrective measures 1
• Consider hydrocortisone 200 mg daily for persisting hypotensive shock 1

Intracranial Pressure Management

• Implement basic measures to control suspected or proven raised intracranial pressure and maintain cerebral perfusion pressure 1
• Strongly consider intubation for Glasgow Coma Scale <12 1
• Do not restrict fluids in an attempt to reduce cerebral edema—this approach is not recommended 1
• Routine ICP monitoring is not recommended 1

Interventions to Avoid

• Do not use glycerol: Trials in Malawi showed increased mortality in adults and no benefit in children 1
• Do not use induced hypothermia: A randomized trial was stopped prematurely due to excess mortality 1

Common Pitfalls and Caveats

• Do not administer dexamethasone if antibiotics were started >12 hours ago, as this represents inappropriate steroid exposure without likely benefit 8, 5
• When dexamethasone is used in pneumococcal meningitis, consider adding rifampin to the empiric regimen because dexamethasone may reduce vancomycin CSF penetration 1, 2
• Careful monitoring is essential to detect adverse outcomes, particularly in patients with highly penicillin- and cephalosporin-resistant pneumococci 1
• Treat suspected or proven seizures early, and use EEG monitoring for patients with fluctuating consciousness or subtle abnormal movements to detect non-convulsive status epilepticus 1
• The benefit of dexamethasone appears confined to high-income countries with well-resourced healthcare systems; studies from resource-limited settings have not demonstrated benefit 2