A randomized trial comparing the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly patients hospitalized with community-acquired pneumonia.
BACKGROUND
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.


OBJECTIVE
To assess the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly patients hospitalized with CAP.


METHODS
Prospective, randomized, double-blind trial conducted at 47 hospitals in the United States.


METHODS
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.


METHODS
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.


METHODS
The primary safety end point was a composite of ventricular arrhythmia events based on Holter monitoring.


RESULTS
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.


CONCLUSIONS
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.
Morganroth
Joel
J
University of Pennsylvania School of Medicine and eResearch Technology, Philadelphia, USA. jmorganroth@ert.com
Dimarco
John P
JP
Anzueto
Antonio
A
Niederman
Michael S
MS
Choudhri
Shurjeel
S
D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001372:Aza Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D017714:Community-Acquired Infections / Q000188:drug therapy; D015897:Comorbidity; D004311:Double-Blind Method; D015716:Electrocardiography, Ambulatory; D005260:Female; D024841:Fluoroquinolones; D006329:Heart Conduction System / Q000187:drug effects*; D006760:Hospitalization; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D015242:Ofloxacin / Q000008:administration & dosage / Q000494:pharmacology*; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D011446:Prospective Studies; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D064704:Levofloxacin; D015242:Ofloxacin; D000077266:Moxifloxacin