What are the risks associated with fluoroquinolone (antibiotic) use?

Risks Associated with Fluoroquinolone Use

Fluoroquinolones carry FDA black box warnings for tendon rupture, with the Achilles tendon affected in 90% of cases, and patients over 60 years face a 4-fold increased risk, particularly when combined with corticosteroids (odds ratio 43.2 for Achilles rupture). 1, 2

Musculoskeletal Complications

Tendon Disorders

• Current fluoroquinolone use increases risk of any tendon disorder (odds ratio 1.7), tendon rupture (odds ratio 1.3), and specifically Achilles tendon rupture (odds ratio 4.1). 3
• The absolute risk is approximately 12 additional Achilles tendon ruptures per 100,000 persons within 90 days of treatment. 3
• Symptoms typically occur within 1 week of exposure (median 6 days) but can appear as early as 2 hours after initial dose or as late as 6 months after discontinuation. 3
• Bilateral involvement occurs in more than half of cases. 3
• While the Achilles tendon is most commonly affected (90%), other tendons can be involved including patellar, rotator cuff, flexor hallucis longus, supraspinatus, and hand/foot tendons. 3
• Only 26% of patients fully recover; 74% report persistent pain and disability at follow-up. 3

High-Risk Populations for Tendon Injury

• Age over 60 years: Risk increases to 1 Achilles rupture per 1,638 treated patients (4-fold higher than general population). 3
• Concomitant corticosteroid use: Dramatically escalates risk to 1 rupture per 979 patients (odds ratio 43.2). 3
• Athletes and physically active individuals: 50% of fluoroquinolone-associated tendon disorders occur during sports participation. 3
• Organ transplant recipients (kidney, heart, or lung). 1
• Underlying conditions: Osteoarthritis, rheumatoid arthritis, diabetes mellitus, end-stage renal disease/hemodialysis, gout, hypercholesterolemia. 3, 4

Drug-Specific Risk Variation

• Levofloxacin and ofloxacin possess higher propensities for tendon damage compared to other fluoroquinolones, with risk being exposure-dependent (higher doses and longer durations carry greater risk). 5

Neurologic Complications

Peripheral Neuropathy

• Can occur soon after initiation and may be irreversible. 1
• Symptoms include pain, burning, tingling, numbness, and weakness. 1
• Requires immediate discontinuation upon symptom onset. 1
• Small fiber neuropathy is a recognized manifestation. 6

Central Nervous System Toxicity

• Seizures and convulsions reported, particularly in patients with pre-existing seizure history. 1
• Encephalopathy can occur. 6
• Dizziness, lightheadedness, and increased intracranial pressure (persistent headache with or without blurred vision). 1

Myasthenia Gravis Exacerbation

• Fluoroquinolones are contraindicated in patients with known myasthenia gravis due to risk of severe muscle weakness and respiratory difficulties. 1

Cardiovascular Complications

QT Interval Prolongation

• Patients should inform physicians of personal or family history of QT prolongation, hypokalemia, bradycardia, or recent myocardial ischemia. 1
• Avoid concurrent use with Class IA (quinidine, procainamide) or Class III (amiodarone, sotalol) antiarrhythmic agents. 1

Aortic Complications

• Increased risk of aortic dissection and aneurysm rupture. 6, 7

Metabolic and Organ-Specific Toxicity

• Hepatotoxicity: Severe hepatotoxicity including acute hepatitis and fatal events reported; discontinue immediately if signs of liver injury occur (loss of appetite, nausea, vomiting, jaundice, dark urine). 1
• Disrupted glucose metabolism: Can cause both hypoglycemia and hyperglycemia. 6
• Acute renal failure: Particularly with ciprofloxacin or norfloxacin due to crystallization. 6
• Phototoxicity: Increased sensitivity to sunlight. 6

Gastrointestinal Complications

• Clostridioides difficile infection: Can develop even 2 months or more after last antibiotic dose. 1

Pediatric Considerations

• Long-term 5-year follow-up data showed cumulative musculoskeletal adverse events were slightly higher in comparator groups (2% levofloxacin vs 4% comparator), suggesting acceptable safety profile in children when clinically indicated. 3
• Achilles tendon rupture remains rare in pediatric populations. 3

Critical Management Pitfalls

• Do not delay discontinuation if tendon pain, swelling, or inflammation develops—instruct patients to rest, refrain from exercise, and stop the drug immediately. 1
• Consider magnesium supplementation during fluoroquinolone treatment if no contraindications exist, as recommended by the American College of Physical Medicine and Rehabilitation, since fluoroquinolones chelate magnesium affecting collagen synthesis. 8
• For high-risk patients (over 60, osteoarthritis, athletes, corticosteroid users), strongly consider alternative antibiotic classes when clinically appropriate. 8, 9
• Avoid fluoroquinolones for uncomplicated infections (such as uncomplicated cystitis) unless no other antimicrobial treatment is feasible. 7
• Patients must drink fluids liberally to avoid crystal formation in urine. 1
• Separate administration from antacids containing magnesium/aluminum, sucralfate, iron, zinc, or didanosine by at least 2 hours. 1