What is the recommended antimicrobial therapy for severe meningitis?

Recommended Antimicrobial Therapy for Severe Meningitis

For severe bacterial meningitis, the recommended empiric antimicrobial therapy is ceftriaxone or cefotaxime plus vancomycin, with additional ampicillin for patients over 50 years or immunocompromised to cover Listeria monocytogenes. 1, 2

Initial Management Principles

• Antibiotic therapy should be started as soon as possible after bacterial meningitis is suspected, with time from hospital entry to antibiotic administration not exceeding 1 hour 3
• Blood cultures must be obtained before initiating antibiotics, but should not delay treatment 1
• If lumbar puncture is delayed (e.g., due to need for cranial imaging), empiric treatment must be started immediately upon clinical suspicion 3
• Delay in treatment is strongly associated with increased mortality and poor neurological outcomes 1

Empiric Antimicrobial Therapy by Age Group

Adults <50 years without risk factors for Listeria:

• Ceftriaxone 2g IV every 12 hours OR cefotaxime 2g IV every 4-6 hours 3, 2
• PLUS vancomycin 15-20 mg/kg IV every 8-12 hours (to achieve serum trough concentrations of 15-20 μg/mL) OR rifampicin 300 mg every 12 hours 3

Adults ≥50 years or immunocompromised:

• Ceftriaxone 2g IV every 12 hours OR cefotaxime 2g IV every 4-6 hours 3
• PLUS vancomycin 15-20 mg/kg IV every 8-12 hours (to achieve serum trough concentrations of 15-20 μg/mL) OR rifampicin 300 mg every 12 hours 3
• PLUS amoxicillin/ampicillin 2g IV every 4 hours (for Listeria coverage) 3, 2

Children (1 month to 18 years):

• Cefotaxime 75 mg/kg IV every 6-8 hours OR ceftriaxone 50 mg/kg IV every 12 hours (maximum 2g every 12 hours) 3, 4
• PLUS vancomycin 10-15 mg/kg IV every 6 hours (to achieve serum trough concentrations of 15-20 μg/mL) OR rifampicin 10 mg/kg every 12 hours (up to 600 mg/day) 3

Neonates (<1 month):

• Amoxicillin/ampicillin/penicillin plus cefotaxime, OR amoxicillin/ampicillin plus an aminoglycoside 3, 1
• Dosing for neonates <1 week: cefotaxime 50 mg/kg every 8 hours; ampicillin/amoxicillin 50 mg/kg every 8 hours; gentamicin 2.5 mg/kg every 12 hours 3
• Dosing for neonates 1-4 weeks: ampicillin 50 mg/kg every 6 hours; cefotaxime 50 mg/kg every 6-8 hours; gentamicin 2.5 mg/kg every 8 hours 3

Pathogen-Specific Treatment

Streptococcus pneumoniae:

• If penicillin-sensitive (MIC ≤0.06 mg/L): benzylpenicillin 2.4g IV every 4 hours OR continue ceftriaxone/cefotaxime 3, 5
• If penicillin-resistant but cephalosporin-sensitive: continue ceftriaxone/cefotaxime 3
• If both penicillin and cephalosporin-resistant: continue ceftriaxone/cefotaxime PLUS vancomycin PLUS rifampicin 3, 6
• Duration: 10-14 days (10 days if recovered, 14 days if not recovered by day 10 or resistant strain) 3, 2

Neisseria meningitidis:

• Ceftriaxone 2g IV every 12 hours OR cefotaxime 2g IV every 6 hours OR benzylpenicillin 2.4g IV every 4 hours 3, 2
• Duration: 5-7 days 2, 5

Listeria monocytogenes:

• Amoxicillin 2g IV every 4 hours 2, 5
• Duration: 21 days 2, 5

Haemophilus influenzae:

• Ceftriaxone 2g IV every 12 hours OR cefotaxime 2g IV every 6 hours 2, 5
• Duration: 10 days 2

Special Considerations

• For areas with high pneumococcal resistance to penicillin, the combination of ceftriaxone and rifampicin is preferred over vancomycin when dexamethasone is used, as dexamethasone reduces vancomycin penetration into CSF 6
• Risk factors for Listeria monocytogenes include age >50 years, diabetes mellitus, immunosuppressive drugs, cancer, and other immunocompromising conditions 3, 1
• Consider adjunctive dexamethasone therapy (administered before or with the first antibiotic dose) for suspected bacterial meningitis, especially for pneumococcal meningitis 1, 7

Common Pitfalls to Avoid

• Delaying antibiotics for imaging - antibiotics should be given within 1 hour of presentation even if lumbar puncture is delayed 3
• Inadequate coverage for Listeria in patients >50 years or immunocompromised 1, 2
• Insufficient dosing that doesn't achieve adequate CSF penetration 1
• Neglecting to obtain blood cultures before starting antibiotics 1
• Failing to consider local resistance patterns, especially after recent travel to areas with high pneumococcal resistance 3, 2