Erythromycin Reduces Bronchiectasis Exacerbations, Antibiotic Resistance

SAN FRANCISCO – Long-term, low-dose erythromycin reduces pulmonary exacerbations, sputum production, and breathing problems in patients with non–cystic fibrosis bronchiectasis, according to a randomized, placebo-controlled Australian study.

Low-dose erythromycin also may be less likely than azithromycin to induce antibiotic resistance, the usual choice for antibiotic prophylaxis. For these reasons, erythromycin "should be considered for the management of subjects with" non-CF bronchiectasis, said lead investigator Dr. David Serisier at an international conference of the American Thoracic Society.

A total of 59 nonsmoking adults with the disease were randomized to erythromycin ethylsuccinate 400 mg twice daily and 58 to placebo, for 48 weeks. (The dosage of the better-tolerated salt is the equivalent of 250 mg of erythromycin b.i.d.) All patients had at least two infective exacerbations in the preceding year, said Dr. Serisier, a chest physician and associate professor of medicine at the University of Queensland in Brisbane.

The erythromycin group had almost 40% fewer exacerbations (odds ratio, 0.64; 95% confidence interval [CI], 0.48-0.86; P = .02), corresponding to a mean reduction of 0.7 exacerbations per patient per year. About a third of the erythromycin patients (19) and more than half (30) of the placebo patients had two or more exacerbations during the trial (P = .039). Only one erythromycin patient was withdrawn for possible QTc prolongation at 6 months.

Forced expiratory volume in 1 second (FEV₁) declined slightly in both groups, but more so in the placebo arm, with a treatment effect of 2.02% (95% CI, 0.04-4.2; P = .046) in favor of erythromycin. Erythromycin patients also produced about 6 g less of sputum per day.

By study’s end, about 36% of oropharyngeal streptococci isolates in the erythromycin group were resistant, versus about 5% in the placebo group (P less than .0001). "Erythromycin resulted in a very substantial increase in the proportion of macrolide-resistant streptococci," Dr. Serisier said.

Azithromycin, however, appears to be a more potent inducer of resistance, according to a randomized Belgian trial that found a 53.4% increase (P less than .0001) in macrolide-resistant oral streptococci after just 3 days of treatment (Lancet 2007;369:482-90).

"We are not exactly comparing apples with apples, but there’s a suggestion that this effect is less with erythromycin," even after an entire year of therapy, he said.

Even so, "I think [erythromycin] should be reserved for subjects who have evidence of more severe airway infection. I don’t think it’s something we should be throwing at all non-CF bronchiectasis patients, and [certainly] not those who just have a mild, troublesome cough. I want this drug to be used in patients who really need it," Dr. Serisier said.

Dr. Serisier said he had no relevant disclosures.

SAN FRANCISCO – Long-term, low-dose erythromycin reduces pulmonary exacerbations, sputum production, and breathing problems in patients with non–cystic fibrosis bronchiectasis, according to a randomized, placebo-controlled Australian study.

Low-dose erythromycin also may be less likely than azithromycin to induce antibiotic resistance, the usual choice for antibiotic prophylaxis. For these reasons, erythromycin "should be considered for the management of subjects with" non-CF bronchiectasis, said lead investigator Dr. David Serisier at an international conference of the American Thoracic Society.

A total of 59 nonsmoking adults with the disease were randomized to erythromycin ethylsuccinate 400 mg twice daily and 58 to placebo, for 48 weeks. (The dosage of the better-tolerated salt is the equivalent of 250 mg of erythromycin b.i.d.) All patients had at least two infective exacerbations in the preceding year, said Dr. Serisier, a chest physician and associate professor of medicine at the University of Queensland in Brisbane.

The erythromycin group had almost 40% fewer exacerbations (odds ratio, 0.64; 95% confidence interval [CI], 0.48-0.86; P = .02), corresponding to a mean reduction of 0.7 exacerbations per patient per year. About a third of the erythromycin patients (19) and more than half (30) of the placebo patients had two or more exacerbations during the trial (P = .039). Only one erythromycin patient was withdrawn for possible QTc prolongation at 6 months.

Forced expiratory volume in 1 second (FEV₁) declined slightly in both groups, but more so in the placebo arm, with a treatment effect of 2.02% (95% CI, 0.04-4.2; P = .046) in favor of erythromycin. Erythromycin patients also produced about 6 g less of sputum per day.

By study’s end, about 36% of oropharyngeal streptococci isolates in the erythromycin group were resistant, versus about 5% in the placebo group (P less than .0001). "Erythromycin resulted in a very substantial increase in the proportion of macrolide-resistant streptococci," Dr. Serisier said.

Azithromycin, however, appears to be a more potent inducer of resistance, according to a randomized Belgian trial that found a 53.4% increase (P less than .0001) in macrolide-resistant oral streptococci after just 3 days of treatment (Lancet 2007;369:482-90).

"We are not exactly comparing apples with apples, but there’s a suggestion that this effect is less with erythromycin," even after an entire year of therapy, he said.

Even so, "I think [erythromycin] should be reserved for subjects who have evidence of more severe airway infection. I don’t think it’s something we should be throwing at all non-CF bronchiectasis patients, and [certainly] not those who just have a mild, troublesome cough. I want this drug to be used in patients who really need it," Dr. Serisier said.

Dr. Serisier said he had no relevant disclosures.

SAN FRANCISCO – Long-term, low-dose erythromycin reduces pulmonary exacerbations, sputum production, and breathing problems in patients with non–cystic fibrosis bronchiectasis, according to a randomized, placebo-controlled Australian study.

Low-dose erythromycin also may be less likely than azithromycin to induce antibiotic resistance, the usual choice for antibiotic prophylaxis. For these reasons, erythromycin "should be considered for the management of subjects with" non-CF bronchiectasis, said lead investigator Dr. David Serisier at an international conference of the American Thoracic Society.

A total of 59 nonsmoking adults with the disease were randomized to erythromycin ethylsuccinate 400 mg twice daily and 58 to placebo, for 48 weeks. (The dosage of the better-tolerated salt is the equivalent of 250 mg of erythromycin b.i.d.) All patients had at least two infective exacerbations in the preceding year, said Dr. Serisier, a chest physician and associate professor of medicine at the University of Queensland in Brisbane.

The erythromycin group had almost 40% fewer exacerbations (odds ratio, 0.64; 95% confidence interval [CI], 0.48-0.86; P = .02), corresponding to a mean reduction of 0.7 exacerbations per patient per year. About a third of the erythromycin patients (19) and more than half (30) of the placebo patients had two or more exacerbations during the trial (P = .039). Only one erythromycin patient was withdrawn for possible QTc prolongation at 6 months.

Forced expiratory volume in 1 second (FEV₁) declined slightly in both groups, but more so in the placebo arm, with a treatment effect of 2.02% (95% CI, 0.04-4.2; P = .046) in favor of erythromycin. Erythromycin patients also produced about 6 g less of sputum per day.

By study’s end, about 36% of oropharyngeal streptococci isolates in the erythromycin group were resistant, versus about 5% in the placebo group (P less than .0001). "Erythromycin resulted in a very substantial increase in the proportion of macrolide-resistant streptococci," Dr. Serisier said.

Azithromycin, however, appears to be a more potent inducer of resistance, according to a randomized Belgian trial that found a 53.4% increase (P less than .0001) in macrolide-resistant oral streptococci after just 3 days of treatment (Lancet 2007;369:482-90).

"We are not exactly comparing apples with apples, but there’s a suggestion that this effect is less with erythromycin," even after an entire year of therapy, he said.

Even so, "I think [erythromycin] should be reserved for subjects who have evidence of more severe airway infection. I don’t think it’s something we should be throwing at all non-CF bronchiectasis patients, and [certainly] not those who just have a mild, troublesome cough. I want this drug to be used in patients who really need it," Dr. Serisier said.

Dr. Serisier said he had no relevant disclosures.