From the Guidelines
Meropenem can cause encephalopathy, particularly in patients with risk factors such as renal impairment, advanced age, and history of central nervous system disorders. This is supported by the recent guidelines on acute-on-chronic liver failure, which highlight that several drugs, including meropenem, can cause acute encephalopathy in cirrhosis at standard recommended dosages due to increased serum concentrations 1. The guidelines specifically mention that meropenem, along with other antibiotics such as piperacillin/tazobactam, ciprofloxacin, norfloxacin, and metronidazole, can lead to encephalopathy in patients with cirrhosis.
Key points to consider:
- Meropenem's ability to cross the blood-brain barrier and potentially interfere with GABA neurotransmission can contribute to the development of encephalopathy 1.
- Patients with renal impairment are at higher risk of developing encephalopathy due to decreased renal clearance of meropenem 1.
- Healthcare providers should be aware of the potential for meropenem to cause encephalopathy and monitor patients closely, particularly those with risk factors.
- If a patient develops signs of encephalopathy while on meropenem, dose adjustment or switching to an alternative antibiotic should be considered 1.
It is essential to note that the guidelines emphasize the importance of identifying precipitants of acute-on-chronic liver failure, including drug-induced acute encephalopathy, to provide appropriate management and improve patient outcomes 1.
From the FDA Drug Label
5.3 Seizure Potential Seizures and other adverse CNS experiences have been reported during treatment with meropenem for injection. The FDA drug label does mention that meropenem can cause seizures and other adverse CNS experiences, which may be related to encephalopathy. However, it does not directly state that meropenem can cause encephalopathy.
- Seizures have been reported in patients with CNS disorders or compromised renal function.
- The overall seizure rate was 0.7% in clinical investigations.
- Dosage adjustment is recommended in patients with advanced age and/or compromised renal function.
- Close adherence to the recommended dosage regimens is urged, especially in patients with known factors that predispose to convulsive activity 2. However, the label does mention delirium as an adverse event that could interfere with mental alertness in patients receiving meropenem for injection 3.
From the Research
Meropenem and Encephalopathy
- Meropenem is a broad-spectrum antibacterial agent of the carbapenem family, used to treat serious bacterial infections 4.
- There have been reports of encephalopathy associated with meropenem use, particularly in patients with underlying central nervous system lesions or multiple sclerosis 5.
- A case report described a 55-year-old female with multiple sclerosis who developed spasticity and encephalopathy within 24 hours of meropenem and ertapenem administration 5.
- Another study found that high-dose meropenem can achieve cerebrospinal fluid (CSF) levels superior to those achieved with commonly recommended dosing regimens, but the patient succumbed to an intracranial bleed 6.
- Meropenem concentrations in brain tissue of neurointensive care patients have been found to exceed CSF levels, suggesting that CSF concentrations may underestimate the target site activity of meropenem beyond the blood-brain barrier 7.
- The safety profile of meropenem has been established through reviews of over 6,000 patients treated with meropenem, with a low incidence of adverse events, including seizures 8.
- However, the incidence of seizures considered related to meropenem treatment was 0.07% in infections other than meningitis, and no new cases of drug-related seizure were reported in updated safety data 8.