A Randomized Trial Comparing the Cardiac Rhythm Safety of Moxifloxacin vs Levofloxacin in Elderly Patients Hospitalized With Community-Acquired Pneumonia
- 30 November 2005
- journal article
- research article
- Published by Elsevier BV in Chest
- Vol. 128 (5), 3398-3406
- https://doi.org/10.1378/chest.128.5.3398
Abstract
Antimicrobial cardiac safety is of particular concern during the treatment of community-acquired pneumonia (CAP) in elderly patients, due to the presence of comorbid conditions and the use of multiple medications that may individually or synergistically affect cardiac repolarization.To assess the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly patients hospitalized with CAP.Prospective, randomized, double-blind trial conducted at 47 hospitals in the United States.Subjects > or = 65 years old with clinical signs/symptoms of CAP requiring initial parenteral therapy, including those with comorbidities. The safety population included 394 patients: 51.3% male; 85.3% white; mean age, 77.8 years. Two-thirds of the patients were > 75 years old, and 74.1% had a history of cardiac disease.Patients received IV/oral moxifloxacin (400 mg qd) or IV/oral levofloxacin (500 mg qd) for 7 to 14 days. Safety evaluations included 72 h of digital continuous 12-lead Holter monitoring, 12-lead ECGs at baseline and at maximum serum concentration on day 3, and adverse events.The primary safety end point was a composite of ventricular arrhythmia events based on Holter monitoring.Holter monitor data were available for 387 patients (192 receiving moxifloxacin and 195 receiving levofloxacin). Sixteen moxifloxacin-treated patients (8.3%) and 10 levofloxacin-treated patients (5.1%) had a primary composite cardiac event (p = 0.29); most events were nonsustained ventricular tachycardia (VT) [14 patients receiving moxifloxacin, 7.3%; and 10 patients receiving levofloxacin, 5.1%]. One moxifloxacin-treated patient had sustained monomorphic VT (> 30 s), and one levofloxacin-treated patient had torsade de pointes. Mean +/- SD QTc (Fridericia formula) change on day 3 was + 6.4 +/- 23.2 ms for moxifloxacin and - 2.5 +/- 22.9 ms for levofloxacin (p = 0.04). No deaths clearly related to study drugs occurred during the observation period.IV/oral moxifloxacin, although known to cause QTc interval prolongation, has a comparable cardiac rhythm safety profile to IV/oral levofloxacin in high-risk elderly patients with CAP.This publication has 22 references indexed in Scilit:
- Drug‐Induced Torsades de Pointes and Implications for Drug DevelopmentJournal of Cardiovascular Electrophysiology, 2004
- Drug-Induced Prolongation of the QT IntervalNew England Journal of Medicine, 2004
- Perioperative Ventricular Dysrhythmias in Patients with Structural Heart Disease Undergoing Noncardiac SurgeryAnesthesia & Analgesia, 1998
- AN ANALYSIS OF THE TIME‐RELATIONS OF ELECTROCARDIOGRAMS.Annals of Noninvasive Electrocardiology, 1997
- Erythromycin-Induced QT Prolongation and Polymorphic Ventricular Tachycardia (Torsades de Pointes): Case Report and ReviewClinical Infectious Diseases, 1994
- Relations of QTc prolongation on the electrocardiogram to torsades de pointes: Definitions and mechanismsThe American Journal of Cardiology, 1993
- Measurement of the QT interval and the risk associated with QTc interval prolongation: A reviewThe American Journal of Cardiology, 1993
- Variability of the QT measurement in healthy men, with implications for selection of an abnormal QT value to predict drug toxicity and proarrhythmiaThe American Journal of Cardiology, 1991
- Role of the electrocardiogram in determining electrophysiologic end points of drug therapyThe American Journal of Cardiology, 1988
- Die Systolendauer im Elektrokardiogramm bei normalen Menschen und bei HerzkrankenActa Medica Scandinavica, 1920