Immunodeficiency: primary or acquired
Background. Lacking protective antibodies, patients with Primary Antibody Deficiencies (PAD) suffer from frequent respiratory infections leading chronic pulmonary damage. Macrolides prophylaxis has been proven effective in chronic respiratory diseases.
Objective: We aimed to test the efficacy and safety of orally administered low-dose azithromycin prophylaxis in PAD patients.
Methods. We designed a three-year, double-blind, placebo-controlled, randomized clinical trial to test whether oral azithromycin (250 mg once daily three-times a week for 2 years) would reduce respiratory exacerbations in PAD with chronic infection-related pulmonary diseases. The primary endpoint was the number of annual respiratory exacerbations. Secondary endpoints included time to first exacerbation, antibiotic additional courses, number of hospitalizations and safety.
Results. Eighty-nine patients received azithromycin (n=44) or placebo (n=45). The number of exacerbations was 3.6 per patient-year (95%CI 2.5-4.7) in the azithromycin arm, and 5.2 (95%CI 4.1-6.4) in the placebo arm (p=0.02). In the azithromycin group the HR for having an acute exacerbation was 0.5 (95%CI 0.3-0.9, p=0.03) and the HR for hospitalization was 0.5 (95%CI 0.2-1.1, p=0.04). The rate of additional antibiotic treatment per patient-year was 2.3 (95%CI 2.1-3.4) in the intervention and 3.6 (95%CI 2.9-4.3) in placebo groups (p=0.004). H. influenzae and S. pneumoniae were the prevalent isolates and they were non-susceptible to macrolides in 25% of patients of both arms. Azithromycin’s safety proﬁle was comparable with placebo.
Conclusion. The study reached the main outcome centered in the reduction of exacerbation episodes per patient-year with a consequent reduction of additional courses of antibiotics, and of risk of hospitalization.