Category: 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.
Cinzia Milito– Sapienza University of Rome
Federica Pulvirenti– Sapienza University of Rome
Francesco Cinetto– Department of Medicine
Maria Carrabba– Department of Internal Medicine Milan
Giovanna Fabio– Department of Internal Medicine Milan
Rosa Maria Dellepiane– Department of Internal Medicine Milan
Carlo Agostini– Department of Medicine
Alessandro Plebani– 3Department of Clinical and Experimental Sciences, University of Brescia and ASST-Spedali Civili of Brescia
Vassilios Lougaris– Department of Clinical and Experimental Sciences, University of Brescia and ASST-Spedali Civili of Brescia
Anna Rosa Soresina– Department of Clinical and Experimental Sciences, University of Brescia and ASST-Spedali Civili of Brescia
Andrea Matucci– Immunoallergology Unit, Department Medical-Geriatric, AOU Careggi
Alessandra Vultaggio– Immunoallergology Unit, Department Medical-Geriatric, AOU Careggi
Giuseppe Spadaro– Department of Translationenter for Basic and Clinical Immunology Research, University of Naples Federico II, Naples
Antonio Pecoraro– Department of Translational Menter for Basic and Clinical Immunology Research, University of Naples Federico II, Naples
Baldassarre Martire– Department of Biomedicine and Evolutive Age, University of Bari
Isabella Quinti– Sapienza University of Rome