- Antibiotics that can cross the blood-brain barrier (BBB) are critical for treating infections of the central nervous system (CNS), such as meningitis, encephalitis, and brain abscesses.
- The BBB is a selective barrier formed by tight junctions between endothelial cells in cerebral capillaries, limiting the entry of many substances, including drugs. However, during CNS infections, the BBB may become more permeable due to inflammation, which can enhance the penetration of certain antibiotics.
- Key factors influencing a drug’s ability to cross the BBB include lipid solubility, molecular size, degree of ionization at physiological pH, protein binding, and the presence or absence of inflammation.
- Among the beta-lactam antibiotics, third-generation cephalosporins such as ceftriaxone, cefotaxime, and ceftazidime are known for their excellent CNS penetration, especially when the meninges are inflamed. These agents are commonly used in the empirical treatment of bacterial meningitis.
- Penicillin G and ampicillin can also reach therapeutic levels in the cerebrospinal fluid (CSF) during inflammation and are particularly important in treating infections caused by Listeria monocytogenes.
- Carbapenems like meropenem and imipenem also have good CNS penetration and are used in resistant or polymicrobial infections, though imipenem carries a higher risk of inducing seizures.
- Chloramphenicol is a highly lipophilic antibiotic that can cross the BBB even without inflammation, making it particularly effective in treating meningitis caused by pathogens like Haemophilus influenzae or Neisseria meningitidis in settings where other treatments are unavailable. However, its use is limited due to the risk of serious adverse effects, including aplastic anemia. Fluoroquinolones, such as ciprofloxacin, levofloxacin, and moxifloxacin, offer moderate to good penetration into the CSF. Moxifloxacin, in particular, has better Gram-positive coverage and is sometimes used in multidrug-resistant CNS infections.
- Metronidazole is another antibiotic with excellent CNS penetration, even in the absence of inflammation. It is the drug of choice for anaerobic brain abscesses, including those caused by Bacteroides or Fusobacterium species. Trimethoprim-sulfamethoxazole (TMP-SMX) also reaches effective concentrations in the CNS and is used to treat infections such as toxoplasmosis and nocardiosis, which often involve the brain in immunocompromised individuals.
- Rifampin, though not typically used alone due to resistance concerns, penetrates the CNS well and is often included in combination regimens for infections like tuberculous meningitis or as prophylaxis for close contacts of patients with meningococcal meningitis. Among antitubercular agents, isoniazid and pyrazinamide have excellent CNS penetration and are essential components of treatment for tuberculous meningitis. Ethambutol and streptomycin, on the other hand, have poorer CNS penetration, especially in the absence of inflammation.
- In contrast, several antibiotics do not achieve therapeutic levels in the CSF under normal circumstances. Aminoglycosides, such as gentamicin and tobramycin, generally do not cross the BBB and must be administered intrathecally or intraventricularly if used for CNS infections. Macrolides (e.g., azithromycin, clarithromycin) and clindamycin also have poor CNS penetration and are not suitable for CNS infections.
