Chest

Chest

Volume 125, Issue 3, March 2004, Pages 953-964
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Clinical Investigations
ANTIBIOTICS
Short-term and Long-term Outcomes of Moxifloxacin Compared to Standard Antibiotic Treatment in Acute Exacerbations of Chronic Bronchitis

https://doi.org/10.1378/chest.125.3.953Get rights and content

Study objectives

To compare the effectiveness of oral moxifloxacin with standard antibiotic therapy in acute exacerbation of chronic bronchitis (AECB).

Design

Multicenter, multinational, randomized, double-blind study of two parallel treatment arms.

Patients

Outpatients ≥ 45 years old with stable chronic bronchitis, smoking history of ≥ 20 pack-years, two or more AECBs in the previous year, and FEV1 < 85% of predicted value. Patients were enrolled when in a stable condition, and patients with exacerbations within 12 months of enrollment were randomized.

Interventions

Randomization (stratified on steroid use) between moxifloxacin (400 mg qd for 5 days) and standard therapy (amoxicillin [500 mg tid for 7 days], clarithromycin [500 mg bid for 7 days], or cefuroxime-axetil [250 mg bid for 7 days]).

Measurements

Assessment at enrollment, randomization (Anthonisen type 1 exacerbation), 7 to 10 days after treatment, and monthly until next AECB or up to 9 months. The primary efficacy variable was clinical success (sufficient improvement, no alternative antimicrobial therapy required) 7 to 10 days after therapy. Secondary predefined end points were clinical cure (return to pre-exacerbation status), further antimicrobial use, time to next AECB, and bacteriologic success.

Results

Three hundred fifty-four patients received moxifloxacin, and 376 patients received standard therapy. At 7 to 10 days after therapy, clinical success rates were similar in intention-to-treat (ITT) patients (95% confidence interval [CI], − 0.7 to 9.5) and per-protocol (PP) patients (95% CI, − 3.0 to 8.5). Moxifloxacin showed superior clinical cure rates over standard therapy in both ITT patients (95% CI, 1.4 to 14.9) and PP patients (95% CI, 0.3 to 15.6), and higher bacteriologic success in microbiologically valid patients (95% CI, 0.4 to 22.1). Fewer ITT patients required antimicrobials after treatment with moxifloxacin than standard therapy (p < 0.01). Time to next exacerbation was longer with moxifloxacin; median and mean times to new AECBs in ITT patients who did not require any further antibiotics were 131.0 days and 132.8 days in moxifloxacin, and 103.5 days and 118.0 days in standard therapy, respectively (p = 0.03). The occurrence of failure, new exacerbation, or any further antibiotic was less frequent in moxifloxacin-treated patients for up to 5 months of follow-up (p = 0.03).

Conclusions

Moxifloxacin was equivalent to standard therapy for clinical success and showed superiority over standard therapy in clinical cure, bacteriologic eradication, and long-term outcomes.

Section snippets

Materials and Methods

This was a multicenter, multinational, randomized, double-blind study of two parallel treatment arms of patients with AECB. Outpatients aged ≥ 45 years with documented chronic bronchitis (CB) were eligible for enrollment during an AECB-free period if they had a history of cigarette smoking of at least 20 pack-years, two or more documented AECBs in the previous year, and FEV1 < 85% of predicted value at the enrollment visit. The main exclusion criteria were previous adverse reaction to study

Results

A total of 1,935 patients were enrolled in 103 centers, 733 of whom were randomized. The randomized and nonrandomized populations were comparable in age, sex, and FEV1, but mean duration of CB and number of AECB episodes in the previous year were significantly greater in the randomized population (Table 1). The trial population profile is shown in Figure 2. In the comparator arm, treatment selection was country dependent, with cefuroxime-axetil being administered from 0 to 65% of comparator

Discussion

In terms of clinical success 7 to 10 days after the end of treatment, 5 days of moxifloxacin was at least as effective as 7 days of conventional antibiotic therapy in all prospectively defined study populations. This result is consistent with previous studies3334 comparing moxifloxacin to different antibiotic regimens. However, this study bears a greater significance for clinical practice, as the design more closely mimicked the real-life practice while maintaining a high degree of internal

MOSAIC Study Group members

Argentina: Horacio Ariza, Luis Horacio Marquez, Lucia Cristina Marzoratti; Australia: David Mackenzie, Charles Mitchell, Matthew Peters, Martin Phillips, Anne-Marie Southcott; Austria: Norbert Vetter; Belgium: Guido Creytens, Jean-Benoit Martinot; Brazil: Alberto Cukier, Luiz Carlos Corrêa Da Silva; Finland: Tuomo Kava, Esko Kurttila, Pekka Saarelainen, Anja Suontausta, Martti Torkko, Kari Venho; France: Nathan Abenhaim, Jacques Allix, Robert Arnou, Martial Boucheret, Nicolas Breton, Pierre

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    • Cited by (0)

    This study was sponsored by Bayer AG.

    Dr. Wilson has received honoraria for presentation from the sponsor.

    Dr. Sagnier is a sponsor staff member.

    †

    A list of participants is given in the Appendix.

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    Copyright © 2004 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.