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

Joel Morganroth, John P. DiMarco, Antonio R Anzueto, Michael S. Niederman, Shurjeel Choudhri

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Context: 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. Study objective: To assess the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly patients hospitalized with CAP. Design and setting: Prospective, randomized, double-blind trial conducted at 47 hospitals in the United States. Patients: Subjects ≥ 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. Interventions: 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. Main outcome measures: 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.

Original languageEnglish (US)
Pages (from-to)3398-3406
Number of pages9
JournalChest
Volume128
Issue number5
DOIs
StatePublished - Nov 2005

Fingerprint

Levofloxacin
Pneumonia
Safety
Ambulatory Electrocardiography
Ventricular Tachycardia
moxifloxacin
Torsades de Pointes
Signs and Symptoms
Comorbidity
Cardiac Arrhythmias

Keywords

  • Ambulatory ECG monitoring
  • Cardiac repolarization
  • Cardiac safety
  • Community-acquired pneumonia
  • Elderly
  • Levofloxacin
  • Moxifloxacin
  • QTc interval

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

A randomized trial comparing the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly patients hospitalized with community-acquired pneumonia. / Morganroth, Joel; DiMarco, John P.; Anzueto, Antonio R; Niederman, Michael S.; Choudhri, Shurjeel.

In: Chest, Vol. 128, No. 5, 11.2005, p. 3398-3406.

Research output: Contribution to journalArticle

Morganroth, Joel ; DiMarco, John P. ; Anzueto, Antonio R ; Niederman, Michael S. ; Choudhri, Shurjeel. / A randomized trial comparing the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly patients hospitalized with community-acquired pneumonia. In: Chest. 2005 ; Vol. 128, No. 5. pp. 3398-3406.
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abstract = "Context: 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. Study objective: To assess the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly patients hospitalized with CAP. Design and setting: Prospective, randomized, double-blind trial conducted at 47 hospitals in the United States. Patients: Subjects ≥ 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. Interventions: 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. Main outcome measures: 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.",
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AU - Choudhri, Shurjeel

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N2 - Context: 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. Study objective: To assess the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly patients hospitalized with CAP. Design and setting: Prospective, randomized, double-blind trial conducted at 47 hospitals in the United States. Patients: Subjects ≥ 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. Interventions: 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. Main outcome measures: 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.

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KW - Ambulatory ECG monitoring

KW - Cardiac repolarization

KW - Cardiac safety

KW - Community-acquired pneumonia

KW - Elderly

KW - Levofloxacin

KW - Moxifloxacin

KW - QTc interval

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