Does cefepime (Cefepime, a fourth-generation cephalosporin antibiotic) cross the blood-brain barrier?

From the Guidelines

Cefepime does cross the blood-brain barrier, but its penetration is limited and variable, especially in the absence of meningeal inflammation. The most recent and highest quality study, published in 2019 1, suggests that the large majority of beta-lactam antibiotics, including cefepime, have limited diffusion through the blood-brain barrier. However, in cases of central nervous system infection, such as meningitis or encephalitis, the penetration of cefepime into the cerebrospinal fluid (CSF) may be increased due to inflammation.

• The study recommends performing beta-lactam therapeutic drug monitoring (TDM) in CSF samples to assess drug diffusion into the brain and ensure adequate antibiotic exposure 1.
• Cefepime's ability to cross the blood-brain barrier is influenced by its chemical properties, such as low molecular weight, low protein binding, and moderate lipophilicity.
• For CNS infections like bacterial meningitis, standard dosing of cefepime is typically 2 grams intravenously every 8 hours in adults with normal renal function, with dose adjustments needed for patients with renal impairment.
• It is essential to note that cefepime's penetration into the CSF can be unpredictable, and individual TDM may be necessary to ensure therapeutic concentrations are achieved 1.
• Another study published in 2004 1 provides guidelines for the management of bacterial meningitis and recommends cefepime as an alternative therapy for certain microorganisms, but it does not specifically address the issue of blood-brain barrier penetration.

From the FDA Drug Label

Data suggest that cefepime does cross the inflamed blood-brain barrier. The clinical relevance of these data is uncertain at this time.

• Cefepime is able to cross the inflamed blood-brain barrier, but the clinical relevance of this is uncertain 2.
• No conclusion can be drawn regarding the ability of cefepime to cross a non-inflamed blood-brain barrier.

From the Research

Cefepime and Blood-Brain Barrier Penetration

• Cefepime is a fourth-generation cephalosporin antibiotic that has been studied for its ability to cross the blood-brain barrier (BBB) and penetrate into the central nervous system (CNS) 3, 4.
• Studies have shown that cefepime can penetrate into the CNS, with variable penetration rates ranging from 4-34% based on area under the curve and 5-58% based on minimum concentration 3.
• The concentration of cefepime in cerebrospinal fluid (CSF) can reach therapeutic levels, exceeding the minimum inhibitory concentrations (MICs) of common pathogens, making it a potential treatment option for CNS infections 3, 4.
• Neurotoxicity, including delirium, has been attributed to cefepime's ability to cross the BBB and produce gamma-aminobutyric acid antagonism 5.

Comparison with Other Antibiotics

• The penetration of cefepime into the CNS is similar to that of other cephalosporins used to treat meningitis 3.
• Meropenem, another antibiotic, has been studied for its penetration into CSF, with maximal percent penetration ranging from 14.3% to 30.9% depending on the dosing regimen 6.

Clinical Implications

• Cefepime may be a useful treatment option for CNS infections, including meningitis, due to its ability to penetrate into the CNS and reach therapeutic levels in CSF 3, 7, 4.
• However, clinicians should be aware of the potential for neurotoxicity, including delirium, and monitor patients closely for adverse effects 5.