Which antibiotic could increase protein in the cerebrospinal fluid (CSF)?

From the Guidelines

Ceftriaxone is the antibiotic that could raise protein in the CSF, as it is commonly used to treat neurologic manifestations of Lyme disease, including meningitis, which can affect CSF protein levels. The use of ceftriaxone for treating Lyme disease with neurologic manifestations is recommended by the Infectious Diseases Society of America 1. Key points to consider include:

• Ceftriaxone is administered intravenously, which can have a direct impact on the central nervous system and potentially affect CSF composition, including protein levels.
• The dosage of ceftriaxone for adult patients with early Lyme disease and acute neurologic manifestations is 2 g once per day intravenously for 14 days, which may influence CSF protein concentrations due to its mechanism of action and the duration of treatment.
• Alternative antibiotics such as cefotaxime or penicillin G may also be used, but ceftriaxone is specifically highlighted for its efficacy in treating neurologic manifestations of Lyme disease, suggesting its potential impact on CSF protein levels 1.
• It is essential to monitor patients receiving ceftriaxone for signs of increased intracranial pressure, which can be indicated by the presence of papilledema or sixth cranial nerve palsy, as elevated intracranial pressure may require additional management strategies beyond antibiotic therapy 1.

From the FDA Drug Label

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

• Ceftriaxone could raise protein in the CSF is not directly stated, however, it mentions protein supplementation in the context of treating CDAD.
• The FDA label does mention that neurological adverse reactions have been reported, including encephalopathy and seizures, but does not directly state that ceftriaxone raises protein in the CSF 2.

From the Research

Antibiotics and CSF Protein Levels

• The relationship between antibiotics and protein levels in cerebrospinal fluid (CSF) is complex and depends on various factors, including the type of antibiotic, the presence of inflammation, and the integrity of the blood-brain barrier 3, 4.
• Ceftriaxone, a third-generation cephalosporin, has been shown to penetrate into the CSF and achieve therapeutic concentrations, especially in the presence of inflammation 4, 5.
• The penetration of ceftriaxone into the CSF is influenced by the degree of inflammation, with higher levels of inflammatory markers (such as C-reactive protein and fibrinogen) associated with increased penetration 4.
• Other antibiotics, such as cefotaxime, also penetrate into the CSF, although the extent of penetration may vary depending on the specific antibiotic and the individual patient's characteristics 3.

Factors Affecting Antibiotic Penetration into CSF

• The blood-brain barrier plays a crucial role in regulating the entry of antibiotics into the CSF, with lipophilic and low-molecular-weight compounds more likely to penetrate 6.
• Inflammation can disrupt the blood-brain barrier, allowing antibiotics to penetrate more easily into the CSF 4, 6.
• Plasma protein binding can also affect antibiotic penetration, with highly bound antibiotics less likely to enter the CSF 5, 6.

Clinical Implications

• The use of intrathecal antibiotics, such as ceftriaxone, may be considered as an adjunct treatment option for central nervous system infections, especially in cases where systemic antibiotics are ineffective or unable to penetrate the CSF 7.
• The choice of antibiotic and dosing regimen should be individualized based on the specific patient's needs and the suspected or confirmed pathogen 5, 7.