Can Levoflox (Levofloxacin) cause delirium?

Can Levofloxacin Cause Delirium?

Yes, levofloxacin can cause delirium and other serious central nervous system effects including hallucinations, confusion, and psychosis, though this is an underrecognized and underdiagnosed adverse effect.

FDA-Recognized CNS Effects

The FDA drug label explicitly warns that levofloxacin can cause significant central nervous system toxicity 1:

• CNS stimulation effects may occur after the first dose and include: confusion, hallucinations, paranoia, depression, nightmares, insomnia, anxiety, restlessness, tremors, and lightheadedness 1
• Severe neuropsychiatric reactions include toxic psychoses, increased intracranial pressure, and rarely suicidal thoughts or acts 1
• The drug should be discontinued immediately if these CNS reactions occur 1

Clinical Evidence of Levofloxacin-Induced Delirium

While the FDA label acknowledges CNS effects, published case reports reveal that delirium specifically is severely underreported 2, 3:

• Only 8-9 cases of levofloxacin-induced delirium had been published in the medical literature as of 2019, despite levofloxacin being widely prescribed 2, 4, 3
• Three cases came from a single medical ward, suggesting this complication is "much more common than previously reported" and reflects "extreme under-recognition and under-diagnosis" 2
• Delirium has occurred in patients ranging from 38 to elderly, including those with and without underlying psychiatric conditions 4, 5

High-Risk Populations

Particular caution is warranted in patients with 1, 5, 6:

• Renal insufficiency - levofloxacin is 80% renally cleared, and accumulation increases neurotoxicity risk 7, 6
• Pre-existing CNS disorders including epilepsy, severe cerebral arteriosclerosis, or conditions that lower seizure threshold 1
• Advanced age - elderly patients have altered pharmacokinetics and increased baseline vulnerability to delirium 7
• Underlying psychiatric conditions - though delirium can be misattributed to worsening mental illness 4

Mechanism and Context

Fluoroquinolones as a class are implicated as medications that can precipitate delirium 7:

• Levofloxacin achieves 16-20% CSF penetration, allowing direct CNS effects 7
• The neurologic adverse effects listed in tuberculosis treatment guidelines include dizziness, insomnia, tremulousness, and headache in 0.5% of patients, but this likely underestimates delirium incidence 7
• Fluoroquinolones (including levofloxacin) are specifically listed among QT-prolonging medications that require monitoring 7

Critical Clinical Pitfall

The most dangerous pitfall is failure to recognize levofloxacin as the cause of new-onset delirium, leading to:

• Unnecessary workup for other causes while the offending agent continues 2, 3
• Misattribution of symptoms to underlying disease progression or psychiatric decompensation 4
• Continued exposure to a potentially fatal complication 2

Delirium often goes unrecognized in up to 70% of cases generally, and drug-induced delirium is frequently missed 2. Physicians must maintain high suspicion for levofloxacin-induced delirium in any patient who develops acute confusion, hallucinations, or behavioral changes after starting this antibiotic 2, 3.

Management Algorithm

When levofloxacin-induced delirium is suspected 1, 2:

1. Immediately discontinue levofloxacin - this is potentially reversible with drug withdrawal 1, 2, 4, 5
2. Provide supportive care and monitor closely for resolution 2, 3
3. Adjust dosing in renal impairment if continuation is absolutely necessary (750-1000 mg three times weekly for CrCl <50 mL/min), though discontinuation is preferred 7
4. Select alternative antibiotic from a different class for ongoing infection treatment 2, 3

The CNS effects are described as "serious but potentially reversible" when the drug is stopped promptly 2, 4, 3.