What is the recommended empirical treatment regimen for meningitis?

Empirical Treatment for Bacterial Meningitis

Start ceftriaxone 2g IV every 12 hours (or cefotaxime 2g IV every 4-6 hours) immediately within 1 hour of presentation, adding ampicillin 2g IV every 4 hours if the patient is ≥60 years old or immunocompromised, and adding vancomycin 15-20 mg/kg IV every 8-12 hours if there is recent travel to areas with penicillin-resistant pneumococci. 1, 2

Critical Timing Principle

• Antibiotic administration must occur within 1 hour of hospital presentation and should never be delayed for lumbar puncture or imaging studies. 1, 2, 3
• Blood cultures must be obtained before antibiotics, but this should not delay treatment beyond the 1-hour window. 1, 2
• Delays in antibiotic treatment are strongly associated with increased mortality and poor neurological outcomes. 1, 4

Age-Based Empirical Regimens

Adults <60 Years (Immunocompetent)

• Ceftriaxone 2g IV every 12 hours OR cefotaxime 2g IV every 4-6 hours provides coverage for Streptococcus pneumoniae and Neisseria meningitidis, the most common pathogens in this population. 1, 3, 5
• Third-generation cephalosporins are the cornerstone because they have bactericidal activity against pneumococci and meningococci with excellent penetration into inflamed meninges. 1, 5

Adults ≥60 Years or Immunocompromised

• Add ampicillin 2g IV every 4 hours to the cephalosporin regimen to cover Listeria monocytogenes, which becomes increasingly prevalent in older adults and immunocompromised patients. 1, 2, 3, 5
• Risk factors for Listeria include diabetes mellitus, immunosuppressive drugs, cancer, alcohol misuse, and other immunocompromising conditions. 1, 5

Additional Coverage for Special Circumstances

Penicillin-Resistant Pneumococci

• Add vancomycin 15-20 mg/kg IV every 8-12 hours (targeting trough concentrations of 15-20 μg/mL) OR rifampicin 600mg IV/PO every 12 hours if the patient has traveled within the past 6 months to areas with high rates of penicillin-resistant S. pneumoniae. 1, 2, 3, 5
• The combination of vancomycin plus ceftriaxone is synergistic against resistant pneumococcal strains and should be used for initial empiric therapy until susceptibility results are available. 6, 7

Severe Penicillin/Cephalosporin Allergy

• Use chloramphenicol 25 mg/kg IV every 6 hours for patients with anaphylaxis history to beta-lactams. 1, 3, 5
• For patients ≥60 years with severe allergy, add co-trimoxazole 10-20 mg/kg (of trimethoprim component) in four divided doses for Listeria coverage. 1, 5

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, 5
• If penicillin-sensitive (MIC ≤0.06 mg/L), may switch to benzylpenicillin 2.4g IV every 4 hours. 1, 5
• If both penicillin and cephalosporin resistant, continue ceftriaxone/cefotaxime plus vancomycin 15-20 mg/kg IV every 12 hours plus rifampicin 600mg every 12 hours. 1

Neisseria meningitidis

• Continue ceftriaxone 2g IV every 12 hours or cefotaxime 2g IV every 6 hours for 5-7 days total. 2, 3, 5

Listeria monocytogenes

• Continue ampicillin 2g IV every 4 hours for 21 days total. 2, 3, 5
• May add gentamicin for synergy in severe cases. 8

Haemophilus influenzae

• Continue ceftriaxone 2g IV every 12 hours or cefotaxime 2g IV every 6 hours for 10 days total. 2, 5

Common Pitfalls to Avoid

• Never delay antibiotics while waiting 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 antibacterial therapy immediately before imaging. 1, 2, 5
• Do not omit ampicillin in patients ≥60 years or immunocompromised—Listeria coverage is essential in these populations and is frequently missed. 1, 2, 5
• Avoid inadequate dosing—use high doses to ensure adequate CSF penetration (ceftriaxone 2g every 12 hours, not lower doses). 1, 9
• Do not stop antibacterial therapy prematurely based on clinical improvement alone—complete the full pathogen-specific duration as microbiological cure does not equal clinical improvement. 2

Adjunctive Dexamethasone Therapy

• Consider dexamethasone as adjunctive treatment, especially for suspected pneumococcal meningitis, administered before or with the first dose of antibacterial therapy. 2, 4, 7
• Dexamethasone inhibits synthesis of inflammatory cytokines and improves outcomes in bacterial meningitis. 7