What are the neurological side effects of ceftriaxone?

October 12, 2025 •

3 min read

Affecting a small subset of patients, neurotoxicity is a rare but serious adverse effect associated with ceftriaxone therapy. This article explores what are the neurological side effects of ceftriaxone, detailing the symptoms, risk factors, and effective management strategies for this medication-induced condition.

Quick Summary

Ceftriaxone can cause rare but significant neurological issues like encephalopathy, seizures, and movement disorders, primarily in high-risk individuals with renal impairment or advanced age. Symptoms often resolve after discontinuing the drug.

Key Points

Encephalopathy: Ceftriaxone can cause encephalopathy, characterized by confusion, altered mental status, disorientation, lethargy, and somnolence.
Seizures and Movement Disorders: More severe neurological side effects include various forms of seizures (including status epilepticus and NCSE) and involuntary muscle jerks known as myoclonus.
Inhibition of GABA Receptors: The neurotoxicity is linked to the drug’s competitive inhibition of GABA, the brain's main inhibitory neurotransmitter, leading to neuronal hyperexcitability.
Renal Impairment is a Major Risk Factor: The most significant predisposing factor is renal impairment, which causes drug accumulation and increases the risk of toxic CNS levels.
Age and Other Factors: Other risk factors include advanced age, high doses, underlying CNS disease, hepatic dysfunction, and low protein levels (hypoalbuminemia).
Diagnosis and Management: Diagnosis relies on clinical suspicion, often supported by an EEG showing encephalopathic changes. The primary treatment is immediate discontinuation of ceftriaxone.
Rapid Resolution: Symptoms typically resolve within a few days of stopping the medication, with supportive care provided as needed.

Understanding Ceftriaxone Neurotoxicity

Ceftriaxone, a third-generation cephalosporin, is widely used but can cause rare neurotoxicity, often due to high concentrations in the central nervous system (CNS). This toxicity results from the drug's beta-lactam ring inhibiting GABA receptors, the brain's main inhibitory neurotransmitter, leading to neuronal hyperexcitability. Impaired drug clearance significantly increases this risk.

Common Neurological Manifestations

Ceftriaxone-induced neurotoxicity can be challenging to diagnose due to non-specific symptoms. Key manifestations include:

Encephalopathy: This is a frequent complication involving altered mental status, confusion, lethargy, and sometimes agitation or fluctuating consciousness.
Seizures: These can range from myoclonic jerks to severe generalized tonic-clonic seizures or nonconvulsive status epilepticus, which can be difficult to detect without an EEG.
Movement Disorders: Involuntary movements such as myoclonus and choreoathetosis have been reported.
Psychiatric Symptoms: Some patients may experience confusion, hallucinations, or other psychiatric issues.

Identifying Key Risk Factors

Certain factors significantly increase the risk of ceftriaxone neurotoxicity:

Renal Impairment: This is the primary risk factor, as reduced kidney function impairs drug excretion, leading to accumulation.
Advanced Age: Elderly patients are more susceptible due to decreased organ function.
High Doses: Elevated ceftriaxone doses, especially in vulnerable individuals, increase the likelihood of toxicity.
Pre-existing CNS Conditions: Conditions affecting the blood-brain barrier can increase drug penetration into the brain.
Hepatic Dysfunction: Impaired liver function can contribute to drug accumulation.
Hypoalbuminemia: Low protein levels can increase the amount of free ceftriaxone available to enter the CNS.

Diagnosis and Investigation

Diagnosis requires clinical suspicion and ruling out other causes of neurological symptoms.

Electroencephalogram (EEG): Can help identify abnormal brain activity consistent with encephalopathy or seizures.
Ceftriaxone Level Monitoring: Measuring drug levels in serum and CSF can support the diagnosis.
Exclusion of Other Causes: Important to rule out infections, metabolic issues, or structural brain problems.

Management and Treatment Strategies

The main treatment involves discontinuing ceftriaxone as soon as neurotoxicity is suspected.

Discontinue Ceftriaxone: Symptoms typically resolve within 2-7 days after stopping the drug.
Supportive Care: Manage symptoms as needed; benzodiazepines may be used for seizures.
Consider Alternative Antibiotics: Switch to a less neurotoxic antibiotic.
Hemoperfusion for Severe Cases: In severe instances, particularly with renal failure, hemoperfusion can help clear the drug more effectively than hemodialysis.

Ceftriaxone vs. Other Cephalosporin Neurotoxicity


Feature	Ceftriaxone	Cefepime (a 4th-gen cephalosporin)
Neurotoxicity Prevalence	Reported as less frequent, but likely underdiagnosed.	More frequently reported and often considered a classic cause of cephalosporin neurotoxicity.
Primary Risk Factors	Renal impairment, advanced age, high doses, hepatic dysfunction, hypoalbuminemia, and CNS disease.	Primarily renal impairment, advanced age, and high doses.
Excretion	Dual excretion (renal and biliary). High protein binding (90-95%) makes it poorly dialyzable.	Primarily renal excretion, which increases drug concentration predictably in renal failure.
Onset Time	Typically within 1 to 10 days of starting treatment.	Similar onset time as ceftriaxone.
Management	Prompt discontinuation; hemoperfusion may be effective in severe cases due to high protein binding.	Prompt discontinuation; dosage adjustment is critical for prevention in renal impairment.

Conclusion: Reversible and Manageable

Ceftriaxone-induced neurotoxicity is a rare but potentially serious complication, often presenting as encephalopathy or seizures. Patients with renal or hepatic impairment, advanced age, or existing CNS disorders are at higher risk. Early identification and discontinuation of ceftriaxone typically lead to the resolution of symptoms within a few days. In severe cases, especially with renal failure, interventions like hemoperfusion may aid recovery. Healthcare providers should be aware of the risk factors and signs to ensure timely management. For more information, consult resources such as the National Institutes of Health (NIH).

Frequently Asked Questions

Patients with impaired renal function, especially those with end-stage renal disease (ESRD) or on hemodialysis, face the highest risk. Older adults (over 75 years), individuals receiving high doses, and those with pre-existing central nervous system (CNS) conditions are also highly susceptible.

Yes, ceftriaxone can cause seizures as a neurological side effect. This includes generalized tonic-clonic seizures, status epilepticus, and nonconvulsive status epilepticus (NCSE), particularly in high-risk individuals.

Ceftriaxone-induced encephalopathy is a brain dysfunction caused by the drug, leading to an altered mental state. Symptoms include confusion, lethargy, somnolence, disorientation, and sometimes agitation or hallucinations. It is often misdiagnosed as other forms of delirium.

The onset of neurological symptoms typically occurs within one to ten days after beginning ceftriaxone treatment. For many patients in serious case reports, the median onset time was around four days.

The main treatment is the immediate discontinuation of ceftriaxone. Symptoms usually resolve completely within a few days after the drug is stopped. Supportive care is provided, and benzodiazepines may be used to control acute seizures.

Yes, hemoperfusion can be an effective treatment for severe ceftriaxone-induced neurotoxicity, especially in patients with end-stage kidney disease. Due to ceftriaxone's high protein binding, it is not effectively removed by standard hemodialysis, but hemoperfusion can accelerate its elimination.

In most reported cases, the neurological side effects are fully reversible once the medication is discontinued. Prompt recognition and treatment are key to a full recovery.