Central nervous system effects of clarithromycin, beta-lactams, and fluoroquinolones occur because of their GABA-A antagonist action. Agents that have dose dependent activity include: Linezolid, which can exhibit CNS activity via its monoamine oxide (MAO) inhibitor activity; metronidazole, which causes neuropsychiatric effects with cumulative or supratherapeutic levels; and tetracyclines, which are more likely to cause CNS effects in patients with reduced CYP2C19 activity.
Nearly all antibiotic agents have been associated with CNS effects. Although uncommon, these events can be severe. Once the antibiotic is discontinued, effects are usually reversible. It is important for mental health care providers to recognize antibiotics as a potential cause of neuropsychiatric adverse effects, as discontinuation often leads to rapid recovery.
Beta-lactams include penicillins, cephalosporins, and carbapenems. Generally, they are considered broad spectrum antibiotic agents that may act as GABA-A antagonists in a dose dependent fashion to produce neurotoxicity. The beta-lactam ring is structurally similar to the GABA antagonist bicuculline. CNS effects include seizures, encephalopathy, tremors, hyperactivity, and excitability.
Penicillins. Piperacillin/tazobactam and ampicillin are the penicillins most likely to contribute to CNS adverse effects. Quinton and colleagues1 examined the effects of a piperacillin/tazobactam continuous infusion and found symptoms such as decreased level of consciousness, delayed awakening after sedation cessation, myoclonus, seizures, and hallucinations. The onset of piperacillin/tazobactam neurotoxicity is usually within seven days, with renal impairment as a predisposing factor. Ampicillin neurotoxicity is more likely to occur in low-birthweight infants where there is increased permeability of the blood-brain barrier.
Cephalosporins. Cefepime and ceftazidime are the most common cephalosporins to cause nonconvulsive status epilepticus, which presents as altered mental status. In critically ill patients, myoclonus and decreased consciousness were the most common symptoms of cefepime- associated neurotoxicity.2 Renal impairment appears to be the largest risk factor, and discontinuation of the cephalosporin results in resolution of symptoms.3,4
Carbapenems. Carbapenems are associated with seizure activity because of its antagonism of the GABA-A receptor.5 Risk factors for seizure activity include renal insufficiency, advanced age, history of seizures, and stroke. Ertapenem has been associated with psychosis—patients have presented with delusions and both visual and auditory hallucinations. Neurotoxicity from ertapenem can persist for up to 14 days after discontinuation. Meropenem and ertapenem may also cause delirium.
Dr Skelly is a Clinical Pharmacist, Pharmacy Department and Department of Psychiatry; Dr Wattengel is a Clinical Pharmacist, Pharmacy Department and Department of Infectious Diseases, Dr Starr is is a Clinical Pharmacist, Pharmacy Department, Dr Sellick is a Medical Doctor, Department of Infectious Diseases, and Dr Mergenhagen is a Clinical Pharmacist, Pharmacy Department and Department of Infectious Diseases, Veteran Affairs Western New York Healthcare System, Buffalo, NY.
The authors report no conflicts of interest concerning the subject matter of this article.
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