The neurotoxic adverse effects of antibiotics are of major concern since they result in significant morbidity and mortality. ​​​​​​Physicians are required to be aware of the neurotoxic effects of antibiotics because a large number of events can be reversed if detected early.

Antibiotics are one of the most commonly prescribed medicines in any clinical setting but apart from their indisputable benefits, they also come with some adverse effects- neurotoxicity being one of them. The elderly (especially those suffering from renal insufficiency), and patients who have issues with their central nervous system (CNS) are usually the ones to more commonly experience neurotoxicity.

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Aminoglycosides

1. The neurotoxic complications depend on the dose of the aminoglycoside given and are commonly seen in those patients with increased CNS permeability.
2. Ototoxicity is the most frequent neurotoxic side effect associated with aminoglycoside besides peripheral neuropathy, encephalopathy, and neuromuscular and autonomic transmission blockade.
3. In patients suffering from myasthenia gravis or Lambert Eaton myasthenic syndrome, giving aminoglycosides may aggravate neuromuscular weakness and can cause morbidity and even mortality since their neuromuscular blocking effects may be compounded.

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Penicillin

Penicillin-induced neurotoxicity is mainly caused by an inhibitory effect on gamma-aminobutyric acid (GABA) transmission. Popular neurotoxic antibiotics include the penicillins such as benzylpenicillin, penicillin G, piperacillin, ticarcillin, ampicillin, amoxicillin, and oxacillin.

1. Psychological disturbance, confusion, disorientation, myoclonus, seizures, encephalopathy, and nonconvulsive status epilepticus are some of the neurotoxic complications with penicillins.
2. Central nervous system (CNS) diseases, renal insufficiency, low-birth weight of newborn, and increased blood-brain barrier permeability are several risk factors that can be related to penicillin-induced neurotoxicity.

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Cephalosporins

Neurotoxicity can be seen with all four generations of cephalosporins. Cefazolin, cefoselis, ceftazidime, cefoperazone, and cefepime are the cephalosporins with the high-risk agents of neurotoxicity. The potential of causing neurotoxic side effects is lesser with cephalexin, cefotaxime, and ceftriaxone. GABA release from the nerve terminals, greater levels of excitatory amino acid, and the release of cytokine are the causes of cephalosporin-induced neurotoxicity and is similar to how penicillins cause neurotoxicity.

1. Lethargy, tardive seizures, encephalopathy, myoclonus, chorea-athetosis, asterixis, seizures, nonconvulsive status epilepticus, and coma are the symptoms seen clinically in cephalosporin-induced neurotoxicity.
2. Old age, renal dysfunction, prior CNS disease, and large dose of medication in the blood are considered as risk factors for cephalosporin neurotoxicity.

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Carbapenems

Carbapenems belong to another group of beta-lactam antibiotics which consist of imipenem, meropenem, panipenem, ertapenem, doripenem, and ceftaroline. The main causes of neurotoxicity in carbapenems is supposedly an inhibition of GABA-A receptors and probably binding to glutamate.

1. Risk factors considered for carbapenem-induced neurotoxicity include renal insufficiency, CNS infections (meningitis), a seizure history, elderly, and a low body weight.
2. Their neurotoxic side effects include headache, seizures, and encephalopathy.

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Tetracyclines

1. Cranial nerve toxicity and neuromuscular blockage can be caused due to tetracyclines.
2. Benign intracranial hypertension has also been documented due to tetracycline use.

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Trimethoprim/sulfonamides

Old age and a compromised immune status are the leading predisposing factors for trimethoprim/sulfamethoxazole toxicity. The precise reason for the neurotoxicity of trimethoprim/sulfamethoxazole is unknown although it is well known that trimethoprim/sulfamethoxazole easily crosses the CNS barrier.

Due to the paucity of major concomitant diseases and drug interactions in children, and maybe because of a smaller drug dose used for their treatment, trimethoprim/sulfamethoxazole neurotoxicity in children is not as common as it is in adults.

Tremor, delirium, agitation, hallucination, psychosis and encephalopathy is hardly ever seen with trimethoprim/sulfamethoxazole. Even if they do occur, they are temporary neurotoxic effects which settle down themselves after discontinuing the drug.

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Macrolides/azalides

Macrolides/azalides are widely accepted for the treatment of upper respiratory infections. Examples of macrolides/azalides include erythromycin, clarithromycin, azithromycin, and dirithromycin and they may cause ototoxicity via damage of the cochlea. They may also cause CNS depression (confusion, obtundation or CNS excitation (agitation, insomnia, delirium, psychosis), and exacerbation of myasthenia gravis.

It may be necessary to detect their adverse effects early because they can result in permanent damage. The side effects of macrolides/azalides depend on the dose of the drug. Tetracyclic antidepressants, calcium channel blockers, cyclosporine, cisapride, antiepileptics, antiretroviral drugs, and digoxin are some of the drugs which interact with macrolides and may alter their adverse effect profile.

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Quinolones

The CNS effects of quinolones depend on their dose. The neurotoxicity of quinolones is thought to be caused by inhibition of GABA-A receptors in addition to quinolones activation of excitatory NMDA receptors. Even though the specific structure-toxicity relationship is lacking with gemifloxacin, levofloxacin, and moxifloxacin, they are known to cause seizures.

Quinolones are commonly used as antibacterial agents because they have a large number of antimicrobial properties. Apart from this, the neurotoxic adverse effects of ciprofloxacin, norfloxacin, ofloxacin, gemifloxacin, levofloxacin, and gatifloxacin are also recognized.

Headache, seizures, confusion, insomnia, encephalopathy, myoclonus, orofacial dyskinesias, delirium, toxic psychosis, a Tourette-like syndrome, and extrapyramidal manifestations such as gait disturbance, dysarthria, and choreiform movements are many of the side effects of quinolones.

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Metronidazole

Metronidazole is a very commonly used antibiotic that treats a large variety of disorders ranging from local skin lesions to potentially dangerous systemic infections. The neurotoxicity of metronidazole is seen clinically as headache, vertigo, confusion, cerebellar toxicity (ataxia and dysarthria), encephalopathy, optic neuropathy, and peripheral neuropathy. Long-term use of metronidazole causes these adverse effects and these side effects normally settle down after discontinuing the drug.