## Drug of Choice for Bacterial Meningitis **Key Point:** Ceftriaxone (or cefotaxime) is the first-line agent for empirical therapy of bacterial meningitis in non-penicillin-allergic patients. ### Why Ceftriaxone? 1. **Superior CNS Penetration** - Third-generation cephalosporin with excellent blood-brain barrier (BBB) penetration - Achieves adequate CSF concentrations (15–20% of serum levels) even without meningeal inflammation - Penetration improves further with inflamed meninges 2. **Broad Spectrum Coverage** - Covers *Streptococcus pneumoniae* (including penicillin-resistant strains) - Covers *Neisseria meningitidis* - Covers *Haemophilus influenzae* - Does NOT reliably cover *Listeria monocytogenes* (requires ampicillin or TMP-SMX in age >50 or immunocompromised) 3. **Dosing in Meningitis** - 2 g IV every 4–6 hours (higher than non-meningitis infections) - Total daily dose: 8–12 g ### Comparison Table | Agent | BBB Penetration | *S. pneumoniae* | *N. meningitidis* | *H. influenzae* | *Listeria* | Meningitis DOC? | | --- | --- | --- | --- | --- | --- | --- | | Ceftriaxone | Excellent (3rd gen) | ✓ | ✓ | ✓ | ✗ | **Yes** | | Cefotaxime | Excellent (3rd gen) | ✓ | ✓ | ✓ | ✗ | **Yes** | | Ampicillin | Poor | ✓ | ✗ | ✗ | ✓ | No (adjunct only) | | Amoxicillin | Poor (oral) | ✓ | ✗ | ✗ | ✓ | No (oral, inadequate levels) | | Cefaclor | Moderate (2nd gen) | ✓ | ✗ | ✓ | ✗ | No (poor meningitis coverage) | **Clinical Pearl:** In patients >50 years or immunocompromised, add ampicillin (or TMP-SMX) to cover *Listeria*, which is not covered by cephalosporins. **High-Yield:** The third-generation cephalosporins (ceftriaxone, cefotaxime) are superior to first- and second-generation agents for meningitis because of their enhanced BBB penetration and broader spectrum. **Mnemonic:** **3rd Gen = CNS Penetration** — Remember: only 3rd-generation cephalosporins reliably penetrate the BBB for meningitis.
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