Can penicillins (antibiotics) induce delirium?

From the Guidelines

Penicillins can induce delirium, particularly in vulnerable populations such as the elderly or those with pre-existing cognitive impairment. This is evident from clinical guidelines that recommend careful observation rather than antimicrobial treatment in older patients with functional and/or cognitive impairment, bacteriuria, and delirium, suggesting that antibiotics like penicillins may exacerbate or contribute to delirium in these patients 1.

Key Considerations

• The potential for penicillins to induce delirium is a critical consideration in patient management, especially in populations with increased susceptibility to cognitive adverse effects.
• Delirium associated with penicillin use may manifest as confusion, disorientation, and altered consciousness, typically within days of initiating therapy.
• The mechanism is thought to involve the penetration of penicillins into the central nervous system, affecting neurotransmitter function and leading to neuronal hyperexcitability.

Clinical Implications

• Discontinuation or dose reduction of the penicillin is recommended if delirium is suspected to be induced by the antibiotic.
• Alternative antibiotics may be necessary if continued antimicrobial therapy is required, highlighting the need for careful selection of antibiotics based on the patient's risk factors for delirium.
• Clinicians should be vigilant for signs of delirium in patients treated with penicillins, particularly in those with risk factors such as advanced age, renal impairment, or pre-existing neurological conditions, as early recognition and management can significantly impact patient outcomes 1.

From the FDA Drug Label

The manifestations may include agitation, confusion, asterixis, hallucinations, stupor, coma, multifocal myoclonus, seizures and encephalopathy.

Delirium can be considered in the context of confusion, which is a listed manifestation of penicillin G overdose.

• Agitation and confusion are key symptoms that may suggest delirium.
• Hallucinations can also be a feature of delirium. The answer to whether penicillins can induce delirium is yes, in the context of an overdose, particularly in patients with severe renal impairment 2.

From the Research

Penicillins and Delirium

• Penicillins, a class of antibiotics, have been associated with delirium in some studies 3, 4.
• A study published in Neurology in 2016 found that antibiotic-associated encephalopathy (AAE) can be caused by penicillins, among other antibiotics, and can lead to delirium 3.
• Another study published in 1978 mentioned that treatment with penicillins can result in direct toxic effects on the central nervous system, which may involve the neurons and potentially lead to delirium 4.
• However, it is essential to note that the evidence for penicillin-induced delirium is not as extensive as for other antibiotics, such as macrolides 5.
• Other studies have focused on the association between antibiotics and seizures, which can be a symptom of delirium, and have found that unsubstituted penicillins and fourth-generation cephalosporins may increase the risk of seizures 6.
• In general, drug-induced delirium can be managed by recognizing the causative drug, ceasing or reducing its dosage, and providing supportive medical care 7.

Mechanisms and Risk Factors

• The mechanisms underlying penicillin-induced delirium are not fully understood but may involve direct toxic effects on the central nervous system 4.
• Certain risk factors, such as renal dysfunction, brain lesions, and epilepsy, may increase the likelihood of developing delirium or seizures when taking penicillins 6.
• Close monitoring of serum levels and continuous EEG may be necessary for patients with predispositions to seizures or delirium when administered penicillins 6.