Two one-year randomized clinical trials have confirmed that two macrolide antibiotics, erythromycin and azithromycin, reduce the acute exacerbation of non-cystic fibrosis branched lung infections, but at the cost of increased resistance to both drugs. David Serisier and colleagues at the Metre Adult Hospital in South Brisbane, Australia, said that in the BLESS clinical trial, patients treated with daily low-dose erythromycin maintenance had significantly lower rates of acute exacerbation of pulmonary infections than those treated with placebo (1.29 vs 1.97 people/year, incidence rate ratio 0.57, 95% confidence interval 0.42 – 0.77). (JAMA 2013 Mar 27;309(12):1260-7) Similarly, Dr. Josje Altenburg and colleagues at the Alkmaar Medical Center in the Netherlands reported significantly lower median values for acute exacerbations of pulmonary infections in patients on azithromycin in the BAT clinical trial (0 vs 2, P<0.001). < span="">(JAMA 2013 Mar 27;309(12):1251-9) According to the results of both clinical trials, published in the March 27 issue of the Journal of the American Medical Association (JAMA), both drugs improved lung function compared with the placebo group, and azithromycin significantly improved quality of life. However, because increased resistance to macrolides was confirmed in both clinical trials (JAMA 2013 Mar 27;309(12):12 95-6), the authors of both groups urged caution in the use of macrolide therapy in this patient population. This view was repeated in a contemporaneous editorial review written by Dr. Stuart Elborn and Dr. Michael Tunney of Queen’s University Belfast, Northern Ireland. But the review authors also said that given the clinical effectiveness of both drugs and the selection criteria for both clinical trials, “patients with bronchiectasis with two or more episodes of acute exacerbation in the previous year should be considered for macrolide therapy.” Elborn and Tunney also wrote, “Long-term patient use of The effect of macrolides on antibiotic resistance, although unclear, should dissuade clinicians from prescribing macrolides to patients whose clinical characteristics differ from those effective in the study.” Indeed, several approaches, including long-term oral antibiotics, inhaled tobramycin, inhaled corticosteroids, and mucolytics, have consistently failed to prove effective in patients with non-cystic fibrosis bronchiectasis. A previous randomized clinical trial, EMBRACE, demonstrated the effectiveness of azithromycin in reducing the acute exacerbation of pulmonary infections in non-cystic fibrosis bronchiectasis, but treatment lasted only 6 months and there was no systematic evaluation of resistance to macrolides, leaving room for further study. The BLESS clinical trial included 117 nonsmoking patients aged 20-85 years (mean 61 years in the erythromycin group and 64 years in the placebo group) with acute exacerbations of infections requiring systemic antibiotic therapy that had occurred at least 2 times in the previous year. Patients were randomly assigned to the erythromycin 400 mg twice daily group or to the placebo group. The primary outcome was the incidence of acute exacerbation of pulmonary infections as defined by a sustained increase in sputum volume or pus requiring antibiotic administration with new worsening of at least two of the following symptoms: sputum volume, pus, cough, dyspnea, chest pain, and hemoptysis. Serisier and colleagues wrote: “Further studies are needed to assess this possibility: patients with frequently worsening P. aeruginosa infections may represent an appropriate subgroup for the limitations of this treatment.” Active treatment also reduced sputum volume and slowed lung function decline, but had no significant effect on quality of life or 6-minute walk test results. Patients tolerated the treatment well, according to the researchers. There were no deaths and only one serious adverse event (in the placebo group). None of the patients developed new arrhythmias. However, the proportion of oropharyngeal streptococci resistant to macrolides was increased. The median change was 27.7% in the active treatment group and 0.04% in the placebo group (P<0.001). The authors write, "Despite the clinical benefit seen with the application of erythromycin, the increased resistance to erythromycin by commensal oropharyngeal streptococci inhibited their enthusiasm for widespread spread of use." They also acknowledge that the study was conducted at a single center and that the patients represented Australian urban resident patients who developed the disease. As such, they wrote, "Given the potential ecological risks, our study design and results make us strongly opposed to extrapolating these results to a broader range of patients." The BAT clinical trial was conducted at 14 centers in the Netherlands, with 83 adult cases randomized to either the azithromycin 250 mg once daily group or the placebo group, with a mean age of 60 years in the azithromycin group and 65 years in the placebo group. All patients had at least three lower respiratory tract infections in the year prior to study entry. The primary outcome was the number of exacerbations of the infection, which was reduced by active treatment. The percentage of patients with at least 1 exacerbation of infection during the study period was significantly lower in the azithromycin group (46.5% vs. 80%, risk ratio 0.29, 95% confidence limits 0.16-0.51). Like erythromycin, azithromycin also improved lung function compared to the placebo group, while it also improved quality of life and symptom scores. Gastrointestinal adverse events, including abdominal pain and diarrhea, were more common in the azithromycin group (40% vs 5%), although there was no difference in the incidence of treatment discontinuation due to suspected adverse effects between the azithromycin and placebo groups, 2.3% in the active treatment group and 2.5% in the placebo group. The incidence of resistance to macrolides was 88% in the azithromycin group and 26% in the placebo group (p<0.001). altenburg and colleagues wrote: "Although the effect on antibiotic resistance needs to be considered, it leads to a better quality of life and may also have an impact on survival".