What are the recommended drugs for treating bacterial meningitis?

Drugs in Bacterial Meningitis

Empiric Antibiotic Therapy

For adults under 50 years without risk factors for Listeria, start ceftriaxone 2g IV every 12 hours (or cefotaxime 2g IV every 4-6 hours) PLUS vancomycin 15-20 mg/kg IV every 8-12 hours to maintain trough concentrations of 15-20 mg/mL, and initiate treatment within 1 hour of presentation. 1, 2

Age-Based Regimens

• Neonates (<1 month): Ampicillin/amoxicillin 50 mg/kg every 6-8 hours PLUS cefotaxime 50 mg/kg every 6-8 hours, or ampicillin plus an aminoglycoside (gentamicin 2.5 mg/kg every 8-12 hours depending on age) 1, 3

• Children (1 month to 18 years): Ceftriaxone 50 mg/kg every 12 hours (maximum 2g every 12 hours) OR cefotaxime 75 mg/kg every 6-8 hours, PLUS vancomycin 10-15 mg/kg every 6 hours to achieve trough concentrations of 15-20 mg/mL, OR rifampin 10 mg/kg every 12 hours (maximum 600 mg/day) 1, 2

• Adults 18-50 years: Ceftriaxone 2g every 12 hours OR cefotaxime 2g every 4-6 hours, PLUS vancomycin 10-20 mg/kg every 8-12 hours OR rifampin 300 mg every 12 hours 1, 4

• Adults >50 years OR immunocompromised: Ceftriaxone 2g every 12 hours OR cefotaxime 2g every 4-6 hours, PLUS vancomycin 10-20 mg/kg every 8-12 hours, PLUS ampicillin 2g every 4 hours for Listeria coverage 1, 2, 4

Critical Timing Considerations

• Antibiotics must be administered within 1 hour of hospital presentation, even if lumbar puncture is delayed 2, 4
• Blood cultures must be obtained before antibiotics, but antibiotic administration should never be delayed beyond 1 hour 2, 4
• If lumbar puncture is delayed for any reason (CT scan, coagulopathy, hemodynamic instability), start empiric antibiotics immediately on clinical suspicion 1, 2

Adjunctive Dexamethasone Therapy

Dexamethasone 10 mg IV every 6 hours (or 0.15 mg/kg every 6 hours in children) should be administered 10-20 minutes before or simultaneously with the first antibiotic dose for all suspected bacterial meningitis cases. 1, 2

Dexamethasone Evidence and Nuances

• Continue dexamethasone for 2-4 days if pneumococcal or H. influenzae meningitis is confirmed 1
• Discontinue dexamethasone if Listeria monocytogenes is identified, as observational data from 252 neurolisteriosis patients showed dexamethasone within 24 hours was associated with increased mortality 1
• For N. meningitidis, there appears to be no harm or benefit, and the decision to continue can be individualized 1
• In adults with pneumococcal meningitis, dexamethasone reduces unfavorable outcomes (26% vs 52%, P=0.006) and mortality (14% vs 34%, P=0.02) 1
• If dexamethasone is not given with the first antibiotic dose, it can still be started up to 4 hours after antibiotics 1

Important Caveat About Dexamethasone and Vancomycin

• Dexamethasone substantially reduces vancomycin penetration into CSF, resulting in delayed CSF sterilization 5
• When using dexamethasone with vancomycin, consider adding rifampin to the empiric regimen (ceftriaxone plus rifampin plus vancomycin) for optimal coverage of resistant pneumococci 1, 5
• The combination of ceftriaxone and rifampin is preferred over ceftriaxone and vancomycin when dexamethasone is used, as rifampin CSF concentrations are not affected by dexamethasone 5

Pathogen-Specific Definitive Therapy

Once culture results and susceptibilities are available, narrow therapy appropriately:

Streptococcus pneumoniae

• Penicillin-sensitive (MIC ≤0.06 mg/mL): Penicillin G 24 million units/day (divided every 4 hours) OR continue ceftriaxone 2g every 12 hours 1, 4
• Penicillin-resistant or cephalosporin-resistant: Continue vancomycin PLUS ceftriaxone, consider adding rifampin especially if dexamethasone is being used 1, 5, 6
• Duration: 10-14 days 4

Neisseria meningitidis

• Penicillin-sensitive: Penicillin G 24 million units/day OR ceftriaxone 2g every 12 hours 1, 4
• Duration: 5-7 days 4
• Chemoprophylaxis: Single dose ciprofloxacin 500mg PO for eradication 2

Listeria monocytogenes

• Ampicillin 2g every 4 hours (12g total daily dose) is the drug of choice 1, 4, 3
• Consider adding gentamicin for synergy in severe cases 3
• Duration: 21 days 4
• Risk factors requiring empiric Listeria coverage: Age >50 years, diabetes mellitus, immunosuppressive drugs, cancer, other immunocompromising conditions 1, 2, 4

Haemophilus influenzae

• Ceftriaxone 2g every 12 hours OR cefotaxime 2g every 6 hours 4, 7
• Duration: 10 days 4

Regional Resistance Considerations

• In areas with high rates of pneumococcal penicillin resistance, vancomycin or rifampin must be added to third-generation cephalosporins for empiric therapy 1, 2
• Local resistance patterns should guide empiric therapy decisions when available 1, 7
• If local S. pneumoniae resistance to penicillin is low, a third-generation cephalosporin alone may be sufficient for adults <50 years without Listeria risk factors 1

Common Pitfalls to Avoid

• Never delay antibiotics for imaging - start treatment within 1 hour even if CT or LP is pending 2, 4
• Never fail to cover Listeria in patients >50 years or immunocompromised - this requires ampicillin addition 2, 4
• Never use vancomycin as monotherapy - it must be combined with a third-generation cephalosporin 1
• Never use suboptimal dosing - high-dose regimens are required for adequate CSF penetration (ceftriaxone 2g every 12h, not once daily for meningitis) 1, 7
• Never neglect blood cultures before antibiotics - obtain them but don't delay treatment 2, 4
• Never stop antibiotics prematurely based on clinical improvement alone - complete the full pathogen-specific duration 4
• Never forget to discontinue dexamethasone if Listeria is identified - it increases mortality in neurolisteriosis 1

Duration of Therapy

• Neisseria meningitidis: 5-7 days total 4
• Streptococcus pneumoniae: 10-14 days total 4
• Haemophilus influenzae: 10 days total 4
• Listeria monocytogenes: 21 days total 4
• Unknown pathogen with clinical recovery: 10 days total 4