What antibiotics can cause delirium?

Antibiotics That Can Cause Delirium

Beta-lactam antibiotics and fluoroquinolones are the antibiotic classes most commonly associated with delirium, with cefepime, cefazolin, and fluoroquinolones like levofloxacin having the highest risk. 1, 2

Beta-Lactam Antibiotics and Delirium

Beta-lactam antibiotics can cause neurological toxicity including delirium through several mechanisms:

• Cefazolin has the highest pro-convulsive activity (294% compared to penicillin G), making it most likely to cause neurological symptoms including delirium 1
• Cefepime has the second highest pro-convulsive activity (160% compared to penicillin G) 1
• Imipenem has significant pro-convulsive activity (71% compared to penicillin G) 1
• Piperacillin and ceftriaxone have lower but still significant neurotoxicity potential 1

Risk Factors for Beta-Lactam Induced Delirium

• Renal failure is the main risk factor for neurological toxicity due to beta-lactam accumulation 1
• High plasma concentrations - specific thresholds associated with neurotoxicity:
  • Cefepime: trough concentrations >22 mg/L (discontinuous infusion) or >35 mg/L (continuous infusion) 1
  • Meropenem: trough concentrations >64 mg/L 1
  • Piperacillin: concentrations >360 mg/L (alone) or >157 mg/L (with tazobactam) 1

Fluoroquinolones and Delirium

Fluoroquinolones are strongly associated with central nervous system effects including delirium:

• Levofloxacin can cause central nervous system stimulation leading to confusion, hallucinations, and delirium 2, 3, 4
• Ciprofloxacin may cause nervousness, agitation, insomnia, anxiety, nightmares, paranoia and other CNS events 5
• Moxifloxacin has been associated with delirium in 4.5% of hospitalized veterans in one study 6

Risk Factors for Fluoroquinolone-Induced Delirium

• Advanced age - each 10-year increase in age was associated with 1.8-fold greater odds of neuropsychiatric events 6
• Concomitant typical antipsychotic use increases risk 5.4-fold 6
• Renal dysfunction may increase risk, particularly with levofloxacin 7
• Pre-existing CNS disorders that predispose to seizures or lower seizure threshold 2

Clinical Presentation and Management

Antibiotic-associated delirium can present with different clinical phenotypes:

• Beta-lactams (especially cephalosporins): encephalopathy commonly accompanied by seizures or myoclonus, arising within days after administration 8
• Fluoroquinolones: encephalopathy characterized by psychosis arising within days of antibiotic administration 8
• Metronidazole: encephalopathy accompanied by cerebellar signs and MRI abnormalities emerging weeks after initiation 8

Management Recommendations

• Immediate discontinuation of the antibiotic at first signs of neurological symptoms 2
• Avoid exceeding plasma free concentrations of beta-lactams above eight times the MIC to prevent neurotoxicity 1
• Consider alternative antibiotics in high-risk patients (elderly, renal dysfunction, CNS disorders) 2, 7
• Monitor renal function and adjust dosing accordingly in patients with renal impairment 1
• Maintain adequate hydration to prevent drug accumulation 5

Special Considerations

• Asymptomatic bacteriuria with delirium: Evidence does not support treating asymptomatic bacteriuria in patients with delirium, as treatment has not been shown to improve mental status and may lead to adverse outcomes including C. difficile infection 1
• Cancer patients with infection-associated delirium: Infection is a frequent precipitating factor for delirium and should be treated if it aligns with patient's goals of care 1
• QT prolongation risk: Many antibiotics that cause delirium (particularly fluoroquinolones) can also prolong QT interval, increasing risk of arrhythmias 1, 2

Remember that delirium is often multifactorial, and antibiotics may be one of several contributing factors. Always consider alternative causes and manage appropriately while discontinuing the offending antibiotic.