Safety of Azithromycin in Wolff-Parkinson-White Syndrome

Risks Associated with Azithromycin in WPW

Azithromycin carries a risk of QT interval prolongation and, rarely, torsades de pointes, though it has a lower risk profile compared to other macrolides such as erythromycin 1
Patients with WPW syndrome are already at risk for dangerous arrhythmias, particularly if they develop atrial fibrillation, which can degenerate into ventricular fibrillation 2

Higher risk WPW patients who should avoid azithromycin include those with a history of symptomatic tachycardia, patients with short RR intervals (<250 ms) during pre-excited atrial fibrillation, patients with multiple accessory pathways 2, 3
Lower risk WPW patients where azithromycin might be considered with caution include patients who have undergone successful catheter ablation of their accessory pathway 2

The primary concern in WPW is not direct QT prolongation but rather medications that might accelerate conduction through the accessory pathway during atrial fibrillation 3, 4
Medications absolutely contraindicated in WPW with pre-excited atrial fibrillation include adenosine, digoxin, nondihydropyridine calcium channel antagonists, and intravenous amiodarone 3, 4

If antimicrobial therapy is necessary in a patient with WPW, obtain a baseline ECG before initiating azithromycin therapy, consider alternative antibiotics without QT-prolonging effects, and monitor for QT prolongation 1
For patients with WPW who develop arrhythmias, immediate direct-current cardioversion is recommended for patients with pre-excited AF and hemodynamic compromise, and intravenous procainamide or ibutilide can be used to restore sinus rhythm in hemodynamically stable patients 4, 2
Catheter ablation of the accessory pathway is the definitive treatment for symptomatic WPW syndrome 2

The risk of sudden cardiac death in WPW is estimated at 0.15-0.2% annually in general WPW patients, but higher (2.2%) in symptomatic patients 2
Approximately 25% of patients with WPW syndrome have accessory pathways with short anterograde refractory periods (<250 ms), which increases the risk of rapid ventricular rates and ventricular fibrillation 3
Even after successful ablation, some patients may still develop atrial fibrillation, requiring continued caution with QT-prolonging medications 3, 2