Effect of Long-term, Low-Dose Erythromycin on Pulmonary Exacerbations Among Patients With Non–Cystic Fibrosis Bronchiectasis

Abstract

HE PATHOPHYSIOLOGY OF NONcystic fibrosis (CF) bronchiectasis is generally considered to be characterized by an airway inflammatory response to bacterial pathogens, and recent data provide further evidence to support this "vicious cycle" hypothesis. 1 However, studies of maintenance therapies designed to interrupt this cycle at differing points have failed to demonstrate convincing evidence of clinical efficacy, including prolonged oral antibiotics, 2 inhaled tobramycin, 3 inhaled corticosteroids, 4 and mucolytics. 5 Until recently, 6 there have arguably been no therapies with proven clinical benefit in non-CF bronchiectasis.Maintenance azithromycin was shown to reduce exacerbations in non-CF bronchiectasis 6 ; however, limitations of that study 7 included a treatment period of only 6 months and a lack of systematic evaluation for macrolide See also pp 1251 and 1295.

The Bronchiectasis Severity Index. An International Derivation and Validation Study

“…No such tool exists for bronchiectasis. New treatments are increasingly available for patients with bronchiectasis, with growing evidence for the efficacy of long-term macrolide therapy and inhaled antibiotics (8)(9)(10)(11). However, these therapies have attendant risks (e.g., antimicrobial resistance and toxicity) as well as significant healthcare costs and treatment burdens (22).…”

“…There is a need to define which patients are most likely to benefit from new treatments, with an increasing number of clinical trials of inhaled and oral therapies in bronchiectasis (8)(9)(10)(11). A severity classification system could theoretically allow targeting of therapies to the patients most likely to benefit.…”

Infections in “Noninfectious” Lung Diseases

“…In the EMBRACE trial, macrolide resistance testing was not performed routinely, but at least two patients had developed macrolide-resistant Streptococcus pneumonia at 6 months (25). A total of 28% of those in the BLESS trial on erythromycin acquired macrolide resistance in oropharyngeal streptococci compared with 0.04% of those on placebo (26). In the BAT trial, 85% of those on azithromycin acquired macrolide resistance in bacterial pathogens versus 26% of those on placebo (27).…”

“…In the BAT trial, 85% of those on azithromycin acquired macrolide resistance in bacterial pathogens versus 26% of those on placebo (27). The clinical importance of this resistance is not yet known; however, macrolides are used to treat many of the organisms that are typically isolated in patients with bronchiectasis, such as H. influenzae, Moraxella catarrhalis, S. pneumonia, Staphylococcus aureus, and nontuberculous mycobacteria (NTM) (25)(26)(27)(28).…”

Long-term Use of Macrolides for Non-cystic Fibrosis Bronchiectasis: The Benefits and Defects

“…In the BLESS trial, 117 patients (58 placebo, 59 erythromycin) were randomized to receive either erythromycin ethylsuccinate 400 mg (250 mg erythromycin base) twice daily, or placebo for 48 weeks [9]. There was a significant reduction of protocol defined exacerbations (PDPEs) in favor of erythromycin group (1.29 in the treatment group vs. 1.97 in the placebo group; IRR, 0.57, 95%CI, 0.42-0.77, p=0.003).…”