Table 1:

Antimicrobial agents. Mechanisms of neurotoxicity and clinical picture.

AB class	Mechanism neurotoxicity	Clinical picture
Beta-lactam	Inhibition of GABA neurotransmission	Increased excitability (high doses)
Penicillins	Non-competitive binding to GABA-A receptors	Confusion, disorientation, hallucinations, myoclonus, and convulsions. Coma in high doses. Hoigne's syndrome (acute psychosis associated with IM procaine benzylpenicillin)
Cephalosporins	Competitive binding to GABA-A receptors High drug penetration in CNS Enhanced glutaminergic activity	Confusion, disorientation, hallucinations, myoclonus, and convulsions. Non-convulsive status epilepticus and language dysfunction potentially mimicking stroke. Cefazolin—headache, dizziness, drowsiness, confusion; Cefuroxime (<1%)—chills, headache, dizziness, drowsiness, irritability, trismus; Ceftazidime—seizures; Ceftriaxone (<1%)—chills, headache, dizziness, seizure; Cefepime (very frequent): encephalopathy, aphasia, myoclonus, seizure, non-convulsive status epilepticus 2 to 4 days after initiation.
Carbapenems	High tissue penetrance Antagonism of GABA-A receptor binding site Interaction with antiepileptic drugs	Seizures, encephalopathy, hallucinations. Neuropsychiatric features (altered mental status) 5 to 7 days after initiation Ertapenem—lower seizure risk (small volume of distribution + high protein binding); Meropenem—lower seizure risk. Additionally causes delirium and myoclonic jerking.
Fluoroquinolones	Inhibition of GABA neurotransmission (structural similarity to GABA) Interference with NMDA	Common: confusion, agitation, insomnia, drowsiness. Less common: hallucinations, suicidal ideation and toxic psychosis; dizziness, restlessness, Rare: seizures 2 to 3 days after initiation
Sulfonamides	Unknown (proposed deficiency in glutathione, secondary deficiency in dopamine and serotonin)	Apathy, depression, aseptic meningitis, ataxia, chills, headache, insomnia, seizures
Macrolides	Unknown (proposed metabolism involving cytochrome P450 3A4)	<1%: Acute psychosis, vertigo, dizziness, drowsiness, headache. Erythromycin—seizures
Metronidazole	Unknown (proposed interference with thiamin pathway, free radical formation). Usually long-term users	Cerebellar symptoms Altered mental status, seizures, peripheral neuropathies and psychosis.
Linezolid	Non-dose-related, weak nonselective monoamine oxidase inhibitor, leading to inhibition of serotonin metabolism Mitochondrial toxicity due to reduced protein synthesis inhibition of monoamine oxidase. Interaction with anticholinergic medications	Serotonin syndrome (agitation, confusion, hyperreflexia), delirium. Peripheral (pain, numbness, paresthesia, weakness) and cranial nerve (optical) neuropathies, when used for >27 days
Aminoglycosides	Activation of NMDA receptors	Numbness, seizure, abnormal gait, ataxia, confusion, headache, lethargy, seizure, vertigo, pseudotumor cerebri Ototoxicity
Polymyxins	Unknown, but dose dependent	Oral parestesia (streptomycin), ataxia and visual disturbances. Seizures, confusion, hallucinations, vertigo
Isoniazid	Reversible, preventable with pyridoxine supplementation, and dose-related—formation of pyridoxal isonicotinyl hydrazine that leads to competitive inhibition of vitamin B6 action	Peripheral neuropathy (most frequent), paresthesia, sensory impairment, seizures, encephalopathy. Optical neuritis.
Ethambutol	Probable formation of pyridoxal isonicotinyl hydrazine that leads to competitive inhibition of vitamin B6 action	Confusion, dizziness, hallucination, headache, peripheral neuritis. Depression and suicidal ideation. Optical neuritis (irreversible blindness reported)