Ceftriaxone-induced Encephalopathy: A Pharmacokinetic Approach

Area of Science:

• Neuroscience
• Pharmacology
• Infectious Diseases

Background:

• Cephalosporin neurotoxicity, particularly with newer generations, is an emerging concern.
• Factors like drug concentration, solubility, and transport influence cephalosporin penetration into the central nervous system.
• The mechanism of beta-lactam neurotoxicity may involve interference with GABAergic neurotransmission.

Purpose of the Study:

• To report a unique case of ceftriaxone-induced encephalopathy.
• To highlight the correlation between high cerebrospinal fluid (CSF) ceftriaxone levels and neurotoxicity.
• To emphasize the limitations of plasma drug monitoring for predicting CSF concentrations.

Main Methods:

• Case report detailing a patient with suspected ceftriaxone-induced encephalopathy.
• Measurement of ceftriaxone concentration in cerebrospinal fluid (CSF).
• Review of literature on cephalosporin neurotoxicity and factors affecting CSF drug levels.

Main Results:

• A patient presented with encephalopathy attributed to ceftriaxone.
• Significantly elevated ceftriaxone levels (27.9 mg/l) were detected in the patient's CSF.
• Plasma drug levels were found to be unreliable indicators of CSF drug concentrations due to inter-individual variability in transport and metabolism.

Conclusions:

• Ceftriaxone dose adjustments and vigilant clinical monitoring are essential for patients with renal impairment.
• Measuring CSF ceftriaxone levels can aid in confirming ceftriaxone-induced encephalopathy.
• This case underscores the importance of considering drug-induced neurotoxicity and direct CSF level monitoring.