Moxifloxacin Proves Noninferior in COPD Exacerbation Tx

CHICAGO – Moxifloxacin works as well as the combination of amoxicillin and clavulanic acid in the treatment of acute exacerbations of complicated chronic obstructive pulmonary disease, new data show. But the former may have the edge in cases in which a bacterial pathogen is identified.

In a randomized, double-blind, noninferiority trial among 1,352 patients who had complicated COPD and an exacerbation, about a fifth of patients had a clinical failure of their antibiotic therapy, no matter which regimen they received, according to results reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

However, secondary analyses showed that in the subset of patients in whom a bacterial pathogen was identified in sputum before antibiotic therapy was started, clinical failure was significantly less likely for those who received moxifloxacin, which is a member of the fluoroquinolone class of antibiotics.

"I think, clinically, what this translates to is, yes, you can use either antibiotic in this group," lead investigator Dr. Sanjay Sethi said in an interview at the conference, which was sponsored by the American Society for Microbiology. But in patients in whom a bacterial pathogen is identified or strongly suspected, "Moxifloxacin does better in that subgroup."

The difference seems to be driven by better bacterial eradication with moxifloxacin, he added. "So when you have a well-defined pathogen, you eradicate the bacterium [and] you get a clinical difference in outcomes."

Both antibiotics were well tolerated, according to Dr. Sethi. Moxifloxacin may have a slight advantage in terms of convenience, as it was given once daily for 5 days, compared with twice daily for 7 days for the amoxicillin–clavulanic acid. Comparative costs will depend on the local market and availability of generic formulations.

Dr. Sethi uses the quinolones as well as amoxicillin plus clavulanic acid. When he is clinically sure that a patient has a predominant pathogen, or when a biomarker such as a C-reactive protein or procalcitonin level indicates "that this could very likely be bacterial, then I would tend to go for the ‘moxi,’ " based on such data, he added.

Some guidelines, such as the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, list the two antibiotic regimens as equal alternatives for patients with complicated COPD, such as those having underlying severe airflow obstruction, recurrent exacerbations, or comorbid cardiac disease, according to Dr. Sethi, chief of the division of pulmonary, critical care, and sleep medicine at the State University of New York at Buffalo.

"What this study tells me is, I think that we did that right," that is, listing the two regimens as alternatives, he commented. "These are secondary analyses, but there could be a subgroup with a predominant pathogen [in whom] there may be differences between the two."

In a novel finding, the study also showed that early bacterial eradication at the end of antibiotic therapy increased the likelihood of clinical cure at 8 weeks later, no matter which antibiotic the patients received. This association "has not been very well described in COPD exacerbations," Dr. Sethi noted.

Patients with COPD were eligible for the trial, called MAESTRAL (Moxifloxacin vs. Amoxicillin–Clavulanic Acid in Treatment of Acute Exacerbation of Chronic Bronchitis), if they were aged 60 years or older, had an Anthonisen type 1 exacerbation (with purulent sputum, increased sputum volume, and increased dyspnea), had an forced expiratory volume in 1 second (FEV₁) of less than or equal to 60% of predicted, and had experienced more than two exacerbations in the last year that required systemic antibiotics and/or systemic corticosteroids.

The subjects were randomized in equal numbers to receive moxifloxacin (400 mg orally once daily for 5 days), or amoxicillin plus clavulanic acid (875 and 125 mg orally twice daily for 7 days). Sputum samples were collected before start of therapy and serially thereafter for Gram staining and culture.

The trial’s primary end point was the rate of clinical failure (defined as the need for additional or alternative treatment for the exacerbation with systemic antibiotics, systemic corticosteroids, and/or hospitalization) within 8 weeks of the end of antibiotic therapy. The investigators defined noninferiority as a difference in the rate of this end point of no more than 6% between groups.

The patients studied were 70 years old on average, and 80% were men. Slightly more than a third used systemic corticosteroids. Their mean FEV₁ was about 980 mL, and their mean number of exacerbations in the previous year had been 2.5.

Study results, reported in a poster session, showed that the rate of clinical failure was noninferior with moxifloxacin, compared with amoxicillin–clavulanic acid, in both the intent-to-treat population (20.4% vs. 21.6%) and the per-protocol population (20.6% vs. 22.0%).

Slightly fewer than half of patients had at least one potentially pathogenic bacterium isolated from sputum before starting antibiotic therapy, most often Haemophilus influenzae, Pseudomonas aeruginosa, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus.

In this subset of patients, the rate of clinical failure was lower with moxifloxacin than with amoxicillin–clavulanic acid in both the intent-to-treat population (19.0% vs. 25.4%; P = .02) and the per-protocol population (19.2% vs. 26.1%; P = .03). Further analysis showed higher rates of bacterial eradication with moxifloxacin, mainly driven by higher rates of eradication of H. influenzae (89.2% vs. 66.7%).

In the study population overall, patients who had bacteriologic eradication at the end of antibiotic therapy, compared with bacteriologic persistence or superinfection, were more likely to be cured 8 weeks later (79.7% vs. 54.7%; P less than .001). The finding was the same in the two treatment groups individually.

The rate of drug-related adverse events was 7.8% with moxifloxacin and 6.1% with amoxicillin–clavulanic acid. The most common events were headache, diarrhea, and fever.

Dr. Sethi reported that he is an investigator for and scientific advisor to Bayer HealthCare Pharmaceuticals, which manufactured the moxifloxacin, and has received speaker honoraria and consulting fees from the company. The trial was supported by Bayer HealthCare Pharmaceuticals.

CHICAGO – Moxifloxacin works as well as the combination of amoxicillin and clavulanic acid in the treatment of acute exacerbations of complicated chronic obstructive pulmonary disease, new data show. But the former may have the edge in cases in which a bacterial pathogen is identified.

In a randomized, double-blind, noninferiority trial among 1,352 patients who had complicated COPD and an exacerbation, about a fifth of patients had a clinical failure of their antibiotic therapy, no matter which regimen they received, according to results reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

However, secondary analyses showed that in the subset of patients in whom a bacterial pathogen was identified in sputum before antibiotic therapy was started, clinical failure was significantly less likely for those who received moxifloxacin, which is a member of the fluoroquinolone class of antibiotics.

"I think, clinically, what this translates to is, yes, you can use either antibiotic in this group," lead investigator Dr. Sanjay Sethi said in an interview at the conference, which was sponsored by the American Society for Microbiology. But in patients in whom a bacterial pathogen is identified or strongly suspected, "Moxifloxacin does better in that subgroup."

The difference seems to be driven by better bacterial eradication with moxifloxacin, he added. "So when you have a well-defined pathogen, you eradicate the bacterium [and] you get a clinical difference in outcomes."

Both antibiotics were well tolerated, according to Dr. Sethi. Moxifloxacin may have a slight advantage in terms of convenience, as it was given once daily for 5 days, compared with twice daily for 7 days for the amoxicillin–clavulanic acid. Comparative costs will depend on the local market and availability of generic formulations.

Dr. Sethi uses the quinolones as well as amoxicillin plus clavulanic acid. When he is clinically sure that a patient has a predominant pathogen, or when a biomarker such as a C-reactive protein or procalcitonin level indicates "that this could very likely be bacterial, then I would tend to go for the ‘moxi,’ " based on such data, he added.

Some guidelines, such as the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, list the two antibiotic regimens as equal alternatives for patients with complicated COPD, such as those having underlying severe airflow obstruction, recurrent exacerbations, or comorbid cardiac disease, according to Dr. Sethi, chief of the division of pulmonary, critical care, and sleep medicine at the State University of New York at Buffalo.

"What this study tells me is, I think that we did that right," that is, listing the two regimens as alternatives, he commented. "These are secondary analyses, but there could be a subgroup with a predominant pathogen [in whom] there may be differences between the two."

In a novel finding, the study also showed that early bacterial eradication at the end of antibiotic therapy increased the likelihood of clinical cure at 8 weeks later, no matter which antibiotic the patients received. This association "has not been very well described in COPD exacerbations," Dr. Sethi noted.

Patients with COPD were eligible for the trial, called MAESTRAL (Moxifloxacin vs. Amoxicillin–Clavulanic Acid in Treatment of Acute Exacerbation of Chronic Bronchitis), if they were aged 60 years or older, had an Anthonisen type 1 exacerbation (with purulent sputum, increased sputum volume, and increased dyspnea), had an forced expiratory volume in 1 second (FEV₁) of less than or equal to 60% of predicted, and had experienced more than two exacerbations in the last year that required systemic antibiotics and/or systemic corticosteroids.

The subjects were randomized in equal numbers to receive moxifloxacin (400 mg orally once daily for 5 days), or amoxicillin plus clavulanic acid (875 and 125 mg orally twice daily for 7 days). Sputum samples were collected before start of therapy and serially thereafter for Gram staining and culture.

The trial’s primary end point was the rate of clinical failure (defined as the need for additional or alternative treatment for the exacerbation with systemic antibiotics, systemic corticosteroids, and/or hospitalization) within 8 weeks of the end of antibiotic therapy. The investigators defined noninferiority as a difference in the rate of this end point of no more than 6% between groups.

The patients studied were 70 years old on average, and 80% were men. Slightly more than a third used systemic corticosteroids. Their mean FEV₁ was about 980 mL, and their mean number of exacerbations in the previous year had been 2.5.

Study results, reported in a poster session, showed that the rate of clinical failure was noninferior with moxifloxacin, compared with amoxicillin–clavulanic acid, in both the intent-to-treat population (20.4% vs. 21.6%) and the per-protocol population (20.6% vs. 22.0%).

Slightly fewer than half of patients had at least one potentially pathogenic bacterium isolated from sputum before starting antibiotic therapy, most often Haemophilus influenzae, Pseudomonas aeruginosa, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus.

In this subset of patients, the rate of clinical failure was lower with moxifloxacin than with amoxicillin–clavulanic acid in both the intent-to-treat population (19.0% vs. 25.4%; P = .02) and the per-protocol population (19.2% vs. 26.1%; P = .03). Further analysis showed higher rates of bacterial eradication with moxifloxacin, mainly driven by higher rates of eradication of H. influenzae (89.2% vs. 66.7%).

In the study population overall, patients who had bacteriologic eradication at the end of antibiotic therapy, compared with bacteriologic persistence or superinfection, were more likely to be cured 8 weeks later (79.7% vs. 54.7%; P less than .001). The finding was the same in the two treatment groups individually.

The rate of drug-related adverse events was 7.8% with moxifloxacin and 6.1% with amoxicillin–clavulanic acid. The most common events were headache, diarrhea, and fever.

Dr. Sethi reported that he is an investigator for and scientific advisor to Bayer HealthCare Pharmaceuticals, which manufactured the moxifloxacin, and has received speaker honoraria and consulting fees from the company. The trial was supported by Bayer HealthCare Pharmaceuticals.

CHICAGO – Moxifloxacin works as well as the combination of amoxicillin and clavulanic acid in the treatment of acute exacerbations of complicated chronic obstructive pulmonary disease, new data show. But the former may have the edge in cases in which a bacterial pathogen is identified.

In a randomized, double-blind, noninferiority trial among 1,352 patients who had complicated COPD and an exacerbation, about a fifth of patients had a clinical failure of their antibiotic therapy, no matter which regimen they received, according to results reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

However, secondary analyses showed that in the subset of patients in whom a bacterial pathogen was identified in sputum before antibiotic therapy was started, clinical failure was significantly less likely for those who received moxifloxacin, which is a member of the fluoroquinolone class of antibiotics.

"I think, clinically, what this translates to is, yes, you can use either antibiotic in this group," lead investigator Dr. Sanjay Sethi said in an interview at the conference, which was sponsored by the American Society for Microbiology. But in patients in whom a bacterial pathogen is identified or strongly suspected, "Moxifloxacin does better in that subgroup."

The difference seems to be driven by better bacterial eradication with moxifloxacin, he added. "So when you have a well-defined pathogen, you eradicate the bacterium [and] you get a clinical difference in outcomes."

Both antibiotics were well tolerated, according to Dr. Sethi. Moxifloxacin may have a slight advantage in terms of convenience, as it was given once daily for 5 days, compared with twice daily for 7 days for the amoxicillin–clavulanic acid. Comparative costs will depend on the local market and availability of generic formulations.

Dr. Sethi uses the quinolones as well as amoxicillin plus clavulanic acid. When he is clinically sure that a patient has a predominant pathogen, or when a biomarker such as a C-reactive protein or procalcitonin level indicates "that this could very likely be bacterial, then I would tend to go for the ‘moxi,’ " based on such data, he added.

Some guidelines, such as the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, list the two antibiotic regimens as equal alternatives for patients with complicated COPD, such as those having underlying severe airflow obstruction, recurrent exacerbations, or comorbid cardiac disease, according to Dr. Sethi, chief of the division of pulmonary, critical care, and sleep medicine at the State University of New York at Buffalo.

"What this study tells me is, I think that we did that right," that is, listing the two regimens as alternatives, he commented. "These are secondary analyses, but there could be a subgroup with a predominant pathogen [in whom] there may be differences between the two."

In a novel finding, the study also showed that early bacterial eradication at the end of antibiotic therapy increased the likelihood of clinical cure at 8 weeks later, no matter which antibiotic the patients received. This association "has not been very well described in COPD exacerbations," Dr. Sethi noted.

Patients with COPD were eligible for the trial, called MAESTRAL (Moxifloxacin vs. Amoxicillin–Clavulanic Acid in Treatment of Acute Exacerbation of Chronic Bronchitis), if they were aged 60 years or older, had an Anthonisen type 1 exacerbation (with purulent sputum, increased sputum volume, and increased dyspnea), had an forced expiratory volume in 1 second (FEV₁) of less than or equal to 60% of predicted, and had experienced more than two exacerbations in the last year that required systemic antibiotics and/or systemic corticosteroids.

The subjects were randomized in equal numbers to receive moxifloxacin (400 mg orally once daily for 5 days), or amoxicillin plus clavulanic acid (875 and 125 mg orally twice daily for 7 days). Sputum samples were collected before start of therapy and serially thereafter for Gram staining and culture.

The trial’s primary end point was the rate of clinical failure (defined as the need for additional or alternative treatment for the exacerbation with systemic antibiotics, systemic corticosteroids, and/or hospitalization) within 8 weeks of the end of antibiotic therapy. The investigators defined noninferiority as a difference in the rate of this end point of no more than 6% between groups.

The patients studied were 70 years old on average, and 80% were men. Slightly more than a third used systemic corticosteroids. Their mean FEV₁ was about 980 mL, and their mean number of exacerbations in the previous year had been 2.5.

Study results, reported in a poster session, showed that the rate of clinical failure was noninferior with moxifloxacin, compared with amoxicillin–clavulanic acid, in both the intent-to-treat population (20.4% vs. 21.6%) and the per-protocol population (20.6% vs. 22.0%).

Slightly fewer than half of patients had at least one potentially pathogenic bacterium isolated from sputum before starting antibiotic therapy, most often Haemophilus influenzae, Pseudomonas aeruginosa, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus.

In this subset of patients, the rate of clinical failure was lower with moxifloxacin than with amoxicillin–clavulanic acid in both the intent-to-treat population (19.0% vs. 25.4%; P = .02) and the per-protocol population (19.2% vs. 26.1%; P = .03). Further analysis showed higher rates of bacterial eradication with moxifloxacin, mainly driven by higher rates of eradication of H. influenzae (89.2% vs. 66.7%).

In the study population overall, patients who had bacteriologic eradication at the end of antibiotic therapy, compared with bacteriologic persistence or superinfection, were more likely to be cured 8 weeks later (79.7% vs. 54.7%; P less than .001). The finding was the same in the two treatment groups individually.

The rate of drug-related adverse events was 7.8% with moxifloxacin and 6.1% with amoxicillin–clavulanic acid. The most common events were headache, diarrhea, and fever.

Dr. Sethi reported that he is an investigator for and scientific advisor to Bayer HealthCare Pharmaceuticals, which manufactured the moxifloxacin, and has received speaker honoraria and consulting fees from the company. The trial was supported by Bayer HealthCare Pharmaceuticals.