From the Guidelines
Both Zosyn (piperacillin-tazobactam) and cefepime can lower the seizure threshold, but cefepime poses a significantly higher risk, particularly in patients with renal impairment. According to the most recent guidelines from the French Society of Pharmacology and Therapeutics and the French Society of Anaesthesia and Intensive Care Medicine 1, cefepime has a lower neurotoxicity threshold than other beta-lactam antibiotics, including Zosyn. The study found that cefepime trough concentrations above 22 mg/L can be associated with neurotoxicity in 50% of patients 1.
Key factors that increase the risk of neurotoxicity and seizures with cefepime include:
- Renal impairment, which can cause rapid accumulation of the drug
- Higher doses
- Advanced age
- Creatinine clearance below 60 mL/min
In contrast, Zosyn (piperacillin-tazobactam) can also cause seizures, but this occurs less frequently than with cefepime, with a higher threshold concentration of 360 mg/L associated with neurotoxicity 1. The mechanism behind these effects involves the beta-lactam structure of both antibiotics, which can antagonize GABA receptors in the brain, disrupting inhibitory neurotransmission and lowering the seizure threshold.
When using either medication, particularly in patients with renal impairment, history of seizures, or neurological disorders, dose adjustment is crucial, and close monitoring for neurological symptoms like confusion, myoclonus, or seizure activity is recommended. If such symptoms develop, prompt discontinuation or dose reduction should be considered, as the risk of neurotoxicity and seizures is a significant concern 1.
From the FDA Drug Label
In addition to the events reported during North American clinical trials with cefepime, the following adverse experiences have been reported during worldwide postmarketing experience. Encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, and non-convulsive status epilepticus have been reported Although most cases occurred in patients with renal impairment who received doses of cefepime that exceeded the recommended dosage schedules, some cases of neurotoxicity occurred in patients receiving an appropriate dosage adjustment for their degree of renal impairment
Cefepime can lower the seizure threshold, as evidenced by reports of seizures, myoclonus, and non-convulsive status epilepticus in patients treated with the drug, particularly those with renal impairment 2.
- Key points:
- Seizures have been reported in patients receiving cefepime
- Neurotoxicity, including seizures, can occur in patients with renal impairment, even with appropriate dosage adjustments The FDA drug label does not provide information on Zosyn (piperacillin/tazobactam) regarding this specific question.
From the Research
Cefepime and Seizure Threshold
- Cefepime has been reported to lower the seizure threshold, particularly in patients with renal impairment or brain disorders 3, 4, 5, 6.
- Studies have shown that cefepime can cause seizures, encephalopathy, and myoclonus, even in patients with normal renal function 3, 6.
- The risk of cefepime-induced neurotoxicity is increased in patients with certain predisposing factors, such as age >65, acute kidney injury, and intensive care unit stay 7.
Zosyn (Piperacillin/Tazobactam) and Seizure Threshold
- There is limited information available on the specific effects of Zosyn (piperacillin/tazobactam) on the seizure threshold.
- However, it is known that penicillins, including piperacillin, can trigger epileptic seizures or status epilepticus by decreasing inhibitory transmission in the brain, thus lowering the seizure threshold 5.
Comparison of Cefepime and Zosyn
- Cefepime has been shown to have a higher risk of neurotoxicity, including seizures, compared to other antibiotics such as meropenem 3.
- There is no direct comparison between cefepime and Zosyn (piperacillin/tazobactam) in terms of their effects on the seizure threshold.
- However, it is recommended to use antibiotics with a low proconvulsive potential and to administer them in an adequately adjusted dose, especially in individuals with renal failure or a history of seizures 5, 7.