## Fluoroquinolone Cardiotoxicity **Key Point:** Moxifloxacin carries the highest risk of QT prolongation among fluoroquinolones due to its greater cardiac potassium channel (hERG) blockade. ### Mechanism of QT Prolongation Fluoroquinolones block cardiac potassium channels (particularly hERG channels), delaying repolarization and prolonging the QT interval. Moxifloxacin's chemical structure (8-methoxy substitution) confers greater channel affinity than earlier-generation agents. ### Relative Cardiac Risk by Agent | Fluoroquinolone | QT Risk | Clinical Significance | | --- | --- | --- | | **Moxifloxacin** | **Highest** | Contraindicated in QT prolongation, electrolyte abnormalities | | Levofloxacin | Moderate | Generally safe at standard doses | | Ciprofloxacin | Low–Moderate | Minimal QT effect | | Ofloxacin | Low–Moderate | Older agent, less commonly used | **High-Yield:** Moxifloxacin should be avoided in patients with: - Baseline QTc > 450 ms (males) or > 460 ms (females) - Hypokalaemia or hypomagnesaemia - Concurrent QT-prolonging drugs (macrolides, antiarrhythmics, antipsychotics) - Female sex (longer baseline QTc) **Clinical Pearl:** Although moxifloxacin has superior respiratory and anaerobic coverage, its cardiac risk often limits use in outpatient settings. Levofloxacin is preferred when fluoroquinolone monotherapy is needed and cardiac safety is a concern. **Warning:** Do not confuse moxifloxacin's superior antimicrobial spectrum with cardiac safety — the two are inversely related in this drug class.
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