Vermeersch K, Gabrovska M, Aumann J, et al. - In an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial, researchers assessed the efficacy of a 3-month intervention with low-dose azithromycin in reducing treatment failure (TF) when started at hospital admission and added to standard care in patients who had been hospitalized for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and had a smoking history of ≥ 10 pack-years and one or more exacerbations in the past year. The participants received azithromycin or placebo within 48 hours of hospital admission, using randomization (1:1). On top of a standardized acute treatment of systemic corticosteroids and antibiotics, they administered the study drug (500 mg/d for 3 d), which was subsequently continued for 3 months (250 mg/2 d). Participants were observed for 6 months thereafter. In the azithromycin group and in the placebo group, the TF rate within 3 months was 49% and 60%, respectively. Within 3 months, treatment intensification rates were 47% vs 60%, step-up in hospital care rates were 13% vs 28%, and mortality rates were 2% vs 4% in the azithromycin and placebo groups, respectively. At 6 months post-withdrawal, the loss of clinical benefits was noted. In patients with an infectious AECOPD requiring hospitalization, a significant reduction in TF during the highest-risk period may be seen in relation to treatment with azithromycin for 3 months. Prolonged therapy appeared necessary to maintain clinical benefits.