Empirical Antibiotic Therapy for Suspected Bacterial Meningitis
Immediate Action Required
Administer antibiotics within 1 hour of hospital presentation—never delay for lumbar puncture or imaging studies. 1, 2, 3
Obtain blood cultures before antibiotics if possible, but this must not delay treatment beyond the 1-hour window. 2, 3
Core Empirical Regimen by Age and Risk Factors
Adults <60 Years (Immunocompetent)
Ceftriaxone 2g IV every 12 hours OR cefotaxime 2g IV every 4-6 hours 1, 2, 3
- This provides coverage for Streptococcus pneumoniae and Neisseria meningitidis, the most common pathogens in this age group 4, 1, 3
- Third-generation cephalosporins are the cornerstone because they achieve bactericidal activity against pneumococci and meningococci with excellent penetration into inflamed meninges 1, 3
Adults ≥60 Years OR Immunocompromised (Any Age)
Ceftriaxone 2g IV every 12 hours OR cefotaxime 2g IV every 4-6 hours PLUS ampicillin 2g IV every 4 hours 1, 2, 3
- The addition of ampicillin is essential for Listeria monocytogenes coverage, which becomes increasingly prevalent in older adults and immunocompromised patients 4, 1, 2
- Risk factors for Listeria include: diabetes mellitus, immunosuppressive drugs, cancer, alcohol misuse, and other immunocompromising conditions 4, 2, 3
Additional Coverage for Resistant Pneumococci
When to Add Vancomycin or Rifampin
Add vancomycin 15-20 mg/kg IV every 8-12 hours (targeting trough concentrations of 15-20 μg/mL) OR rifampin 600mg IV/PO every 12 hours if:
- Recent travel (within 6 months) to areas with high rates of penicillin-resistant S. pneumoniae 1, 3
- Local resistance rates of S. pneumoniae to penicillin are elevated 4
The combination of ceftriaxone plus vancomycin or rifampin has demonstrated synergistic activity against cephalosporin-resistant pneumococcal strains. 5, 6 When dexamethasone is used as adjunctive therapy, ceftriaxone plus rifampin is preferred over ceftriaxone plus vancomycin because dexamethasone substantially reduces vancomycin penetration into CSF and delays sterilization. 7
Pathogen-Specific De-escalation After Culture Results
Streptococcus pneumoniae
- Continue ceftriaxone 2g IV every 12 hours or cefotaxime 2g IV every 4-6 hours for 10-14 days total 1, 2, 3
- If penicillin-sensitive (MIC ≤0.06 mg/L), may switch to benzylpenicillin 2.4g IV every 4 hours 1, 2
Neisseria meningitidis
- Continue ceftriaxone 2g IV every 12 hours or cefotaxime 2g IV every 6 hours for 5-7 days total 1, 2, 3
Listeria monocytogenes
- Continue ampicillin 2g IV every 4 hours for 21 days total 1, 2, 3
- Listeria remains fully susceptible to aminopenicillins 8
Haemophilus influenzae
Adjunctive Dexamethasone Therapy
Start dexamethasone together with the first dose of antibiotics in all cases of suspected bacterial meningitis. 4
- Dexamethasone can still be started up to 4 hours after the first antibiotic dose if not given initially 4
- Adjunctive corticosteroid therapy has demonstrated reduction in mortality and neurologic sequelae in multiple trials and meta-analyses 4
- Consider discontinuation if pathogens other than S. pneumoniae are identified 4
Critical Pitfalls to Avoid
Never delay antibiotics for CT imaging or lumbar puncture. If imaging is indicated (focal neurologic deficits, new-onset seizures, severely altered mental status with GCS <10, or severely immunocompromised state), start antibiotics immediately before imaging. 2, 3
Do not omit ampicillin in patients ≥60 years or immunocompromised. Listeria coverage is essential in these populations and is frequently missed in clinical practice. 2, 3
Avoid inadequate dosing. Use high doses to ensure adequate CSF penetration—ceftriaxone 2g every 12 hours, not lower doses. 3 The FDA-approved dosing for meningitis is up to 4 grams daily in adults. 9
Do not stop antibiotics prematurely based on clinical improvement alone. Complete the full pathogen-specific duration, as clinical improvement does not equal microbiological cure. 2, 3
In neonates, administer intravenous doses over 60 minutes to reduce the risk of bilirubin encephalopathy. 9
Special Considerations for Neonates
For neonates <1 month old: Amoxicillin/ampicillin 50 mg/kg every 4-8 hours (depending on age) PLUS cefotaxime 50 mg/kg every 6-8 hours 4
- Ceftriaxone is contraindicated in premature neonates and in neonates ≤28 days who require calcium-containing IV solutions due to risk of precipitation 9
- The recommended initial therapeutic dose for meningitis in pediatric patients is 100 mg/kg (not to exceed 4 grams), followed by 100 mg/kg/day (not to exceed 4 grams daily) 9