Is Cefepime (a fourth-generation cephalosporin antibiotic) effective for treating acute bacterial meningitis in patients with no known history of beta-lactam allergy?

Cefepime Coverage for Acute Bacterial Meningitis

Cefepime is effective for acute bacterial meningitis caused by the typical pathogens (Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae) and represents a therapeutically equivalent alternative to third-generation cephalosporins like cefotaxime and ceftriaxone. 1, 2

Evidence Supporting Cefepime Efficacy

Clinical trial data demonstrates that cefepime achieves comparable outcomes to standard third-generation cephalosporins:

• A prospective randomized trial of 90 infants and children showed cefepime was therapeutically equivalent to cefotaxime, with similar clinical response rates, cerebrospinal fluid sterilization, complication rates, and mortality (7% overall) 1
• Integrated results from Latin American studies of 345 pediatric patients demonstrated a 75% cure rate with cefepime versus 78% with comparators (cefotaxime or ceftriaxone), with no clinically significant difference 2
• Cefepime achieved CSF concentrations 55 to 95 times greater than the maximal MIC of causative pathogens, ensuring adequate CNS penetration 1

Pathogen-Specific Eradication Rates

Cefepime demonstrates excellent bacteriologic eradication across the major meningitis pathogens:

• Haemophilus influenzae: 97% eradication rate 2
• Neisseria meningitidis: 95% eradication rate 2
• Streptococcus pneumoniae: 92% eradication rate (all tested isolates were penicillin-susceptible) 2

Recommended Dosing

For bacterial meningitis, administer cefepime 50 mg/kg/dose every 8 hours in pediatric patients (2 months to 14 years), with comparable adult dosing of 2g IV every 8 hours. 1, 2

Safety Profile

Cefepime demonstrated a safety profile equivalent to third-generation cephalosporins:

• Audiologic and/or neurologic sequelae occurred in 16% of cefepime-treated patients versus 15% of cefotaxime-treated patients at 2-6 months follow-up 1
• No specific safety concerns were identified in clinical trials 2
• Mortality rates were comparable between cefepime (4.7%) and comparators (8.5%) 1

Clinical Context and Positioning

While cefepime is effective, it is not the preferred first-line agent in current guidelines:

• Current guidelines recommend ceftriaxone 2g IV every 12 hours or cefotaxime 2g IV every 4-6 hours as standard empiric therapy for bacterial meningitis 3
• Cefepime offers no specific advantage over third-generation cephalosporins for typical meningitis pathogens 4
• Cefepime should be considered when third-generation cephalosporins are unavailable or when there are specific institutional preferences, as it provides equivalent efficacy 1, 2

Important Limitations

Cefepime has critical gaps in coverage that must be addressed:

• No activity against Listeria monocytogenes - ampicillin must be added for patients ≥50 years or immunocompromised 3
• Inadequate coverage for penicillin-resistant Streptococcus pneumoniae - vancomycin must be added empirically until susceptibilities are known 3
• Limited data on efficacy against Enterobacter species and Serratia marcescens in meningitis, where treatment failures have occurred with cephalosporins 5

Common Pitfalls to Avoid

• Do not use cefepime monotherapy in patients ≥50 years or immunocompromised without adding ampicillin for Listeria coverage 3
• Always add vancomycin empirically until pneumococcal susceptibilities confirm penicillin/cephalosporin sensitivity 3
• Ensure adequate dosing frequency (every 8 hours) to maintain therapeutic CSF concentrations 1, 2
• Do not delay antibiotic administration beyond 1 hour from presentation, even if lumbar puncture is delayed 3