Table 1.
Comparison of neuropsychiatric toxicity characteristics between antibiotics classes.
| Antibiotic | Blood–brain barrier permeability | Dose dependent | Proposed mechanism of action for neuropsychiatric toxicity | Risk factors | Clinical presentations |
|---|---|---|---|---|---|
| Penicillins | Varies | Yes | Antagonism of GABA-A receptors, direct neurotoxic effect of beta-lactam ring | History of CNS diseases, renal impairment, elderly age | Encephalopathy, behavioural changes, myoclonus, seizures, and, in rare cases, psychosis |
| Cephalosporins | Varies | Yes | Antagonism of GABA-A receptors, direct neurotoxic effect of beta-lactam ring | Renal impairment, pre-existing CNS conditions | Seizures, encephalopathy, occasionally psychosis |
| Carbapenems | Moderate to high | Yes | Antagonism of GABA-A receptors, direct neurotoxic effect of beta-lactam ring | Renal impairment, high doses, CNS disorders | Seizures, confusion, encephalopathy |
| Fluoroquinolones | High | Unknown (occurs at various doses) | Antagonizing GABA-A receptors, NMDA receptor activation | Elderly, concomitant use of NSAIDs or antipsychotics | Insomnia, dizziness, headache, seizures, psychosis |
| Aminoglycoside | Low | Yes (particularly in renal impairment) | NMDA receptor activation | Renal impairment, prolonged therapy, high doses | Ototoxicity and nephrotoxicity more common |
| Macrolides | Varies | Yes | Potential GABA-A antagonism, drug interactions | Pre-existing psychiatric disorders | Hallucinations, mania, delirium, psychosis |
| Trimethoprim/sulfamethoxazole | High | Yes | Potential neuroinflammation, folate pathway interference | Renal impairment, prolonged use, high doses | Delirium, aseptic meningitis, psychosis |
| Oxazolidinones | Moderate to high | Yes (common with prolonged use) | Interaction with monoamine neurotransmitters (monoamine oxidase inhibition) | Coadministration with serotonergic drugs, prolonged use | Serotonin syndrome, peripheral and optic neuropathy |
| Metronidazole | High | Unknown | GABA receptor inhibition, oxidative stress and free radical damage in neurons | High doses, prolonged therapy | Peripheral neuropathy, encephalopathy, seizures |
CNS, central nervous system; GABA, gamma-aminobutyric acid; NSAIDs, non-steroidal anti-inflammatory drugs.