What is the recommended treatment with cefepime (fourth-generation cephalosporin) for a patient with acute bacterial meningitis?

Cefepime for Acute Bacterial Meningitis

Primary Recommendation

Cefepime is NOT recommended as a first-line agent for acute bacterial meningitis; ceftriaxone or cefotaxime are the preferred third-generation cephalosporins, combined with vancomycin for empiric coverage. 1, 2

Evidence-Based Treatment Algorithm

Empiric Therapy (Before Pathogen Identification)

For adults <50 years without Listeria risk factors:

• Ceftriaxone 2g IV every 12 hours OR cefotaxime 2g IV every 4-6 hours 1
• PLUS vancomycin 15-20 mg/kg IV every 8-12 hours 1
• Start within 1 hour of hospital presentation 1, 2

For adults ≥50 years or immunocompromised:

• Ceftriaxone 2g IV every 12 hours OR cefotaxime 2g IV every 4-6 hours 1
• PLUS vancomycin 15-20 mg/kg IV every 8-12 hours 1
• PLUS ampicillin 2g IV every 4 hours (for Listeria coverage) 1, 2

For adults ≥60 years (UK guideline alternative):

• Cefotaxime 2g IV every 6 hours OR ceftriaxone 2g IV every 12 hours 3
• PLUS amoxicillin 2g IV every 4 hours 3
• Add vancomycin 15-20 mg/kg twice daily OR rifampicin 600mg twice daily if penicillin-resistant pneumococci suspected 3

Why Cefepime Is Not Preferred

Critical distinction: While cefepime is a fourth-generation cephalosporin with broader Gram-negative coverage than third-generation agents, guidelines consistently recommend ceftriaxone or cefotaxime as the cephalosporin of choice for bacterial meningitis. 3, 1, 2

The limited pediatric data on cefepime (50 mg/kg/dose every 8 hours) showed comparable efficacy to cefotaxime/ceftriaxone in Latin American studies, with 75% cure rates. 4 However, this does not translate to a guideline recommendation for routine use, as ceftriaxone and cefotaxime have:

• More extensive safety and efficacy data in meningitis 1, 2
• Established CSF penetration profiles 3
• Longer track record in clinical practice 5

Pathogen-Specific Definitive Therapy

For Streptococcus pneumoniae (most relevant to cephalosporin choice):

• Continue ceftriaxone 2g IV every 12 hours OR cefotaxime 2g IV every 6 hours 3, 2
• Duration: 10 days if recovered by day 10; 14 days if slower response or resistant organism 3, 2, 6
• If penicillin-sensitive (MIC ≤0.06 mg/L): can switch to benzylpenicillin 2.4g IV every 4 hours 3, 2

For Neisseria meningitidis:

• Continue ceftriaxone 2g IV every 12 hours OR cefotaxime 2g IV every 6 hours 3, 1
• Duration: 5-7 days 3, 1, 6

For Haemophilus influenzae:

• Continue ceftriaxone 2g IV every 12 hours OR cefotaxime 2g IV every 6 hours 1
• Duration: 10 days 1, 6

For Listeria monocytogenes:

• Switch to amoxicillin 2g IV every 4 hours (cephalosporins are ineffective) 1
• Duration: 21 days 1, 6

Critical Timing and Pitfalls

Time-sensitive actions:

• Obtain blood cultures immediately, but never delay antibiotics 1, 2
• Administer antibiotics within 1 hour of presentation, even if lumbar puncture is delayed for imaging 1, 2
• Delay in treatment strongly correlates with mortality and poor neurological outcomes 1, 2

Common errors to avoid:

• Using cefepime instead of guideline-recommended ceftriaxone/cefotaxime 3, 1, 2
• Omitting ampicillin/amoxicillin in patients ≥50 years or immunocompromised (Listeria coverage) 1, 2
• Stopping antibiotics when fever resolves—complete the full pathogen-specific duration 6
• Shortening pneumococcal meningitis treatment to <10 days 6
• Inadequate vancomycin dosing that fails to achieve CSF penetration (target trough 15-20 μg/mL) 2

Special Considerations

Geographic resistance patterns:

• Add vancomycin or rifampicin if patient traveled to areas with high pneumococcal resistance in past 6 months 3
• Check European Centre for Disease Prevention and Control or WHO data for current resistance patterns 3

Treatment failure at 72 hours:

• Verify adequate vancomycin CSF levels (trough 15-20 μg/mL) 2
• Consider adding rifampicin 600mg IV/PO every 12 hours 2