A 58-year-old man with type 2 diabetes presents with dysuria, frequency, and suprapubic tenderness. Urine culture grows Escherichia coli. He is started on levofloxacin 750 mg once daily. After 3 days of therapy, he develops sudden-onset severe left calf pain and swelling. On examination, there is palpable warmth and tenderness over the left Achilles tendon. What is the most likely adverse effect of the antibiotic?

Explanation

## Fluoroquinolone-Induced Tendinopathy **Key Point:** Fluoroquinolones, particularly older agents like levofloxacin and ciprofloxacin, carry a well-established risk of tendinopathy and tendon rupture, most commonly affecting the Achilles tendon. ### Mechanism of Tendon Injury Fluoroquinolones inhibit bacterial DNA gyrase and topoisomerase IV, but they also: 1. Inhibit human mitochondrial topoisomerase II, impairing collagen synthesis and repair in tendon fibroblasts 2. Increase reactive oxygen species (ROS) production, causing oxidative stress 3. Disrupt calcium homeostasis in tenocytes, leading to apoptosis 4. Impair matrix metalloproteinase regulation, weakening the extracellular matrix ### Risk Factors for Fluoroquinolone Tendinopathy | Risk Factor | Mechanism/Notes | |---|---| | Age > 60 years | Baseline collagen degradation; impaired healing | | Diabetes mellitus | Glycation of collagen; microvascular compromise | | Corticosteroid use | Synergistic collagen weakening | | Renal impairment | Drug accumulation; prolonged exposure | | Intense physical activity | Mechanical stress on weakened tendon | | Previous tendon injury | Pre-existing structural compromise | **Clinical Pearl:** The Achilles tendon is affected in ~60% of fluoroquinolone-induced tendon ruptures, followed by the patellar and rotator cuff tendons. Rupture typically occurs 2–6 weeks after initiation, but can occur acutely. ### Clinical Presentation - Acute or insidious onset of pain, swelling, and warmth over the tendon - Palpable nodule or gap (if rupture) - Positive Thompson test (squeeze calf; no plantar flexion if Achilles rupture) - Inability to plantarflex the foot or walk on tiptoes **High-Yield:** This patient has diabetes and is age 58 — both risk factors. The temporal relationship (3 days into therapy) and classic presentation (Achilles pain + swelling) make fluoroquinolone tendinopathy the diagnosis. ### Management 1. **Immediate:** Discontinue the fluoroquinolone 2. **Imaging:** Ultrasound or MRI to assess tendon integrity 3. **Conservative:** Rest, ice, elevation, NSAIDs (if no contraindication) 4. **Surgical:** Repair if complete rupture confirmed **Warning:** Tendinopathy may progress to rupture even after stopping the drug. Patients must be counseled to avoid strenuous activity during recovery. [cite:KD Tripathi 8e Ch 49]