Relationship between azithromycin susceptibility and administration efficacy for nontypeable Haemophilus influenzae respiratory infection
Euba B (1), Moleres J (2), Viadas C (2), Barberán M (3), Caballero L (2), Grilló MJ (2), Bengoechea JA (4), de-Torres JP (5), Liñares J (6), Leiva J (7), Garmendia J (8).
(1) Instituto de Agrobiotecnología, CSIC-Universidad Pública Navarra-Gobierno Navarra, Mutilva, Spain Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
(2) Instituto de Agrobiotecnología, CSIC-Universidad Pública Navarra-Gobierno Navarra, Mutilva, Spain.
(3) Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain.
(4) Centre for Infection and Immunity, Queen's University Belfast, Belfast, United Kingdom.
(5) Pulmonary Department, Clínica Universidad de Navarra, Pamplona, Spain.
(6) Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain Microbiology Department, Hospital Universitari Bellvitge, IDIBELL, University of Barcelona, Barcelona, Spain.
(7) Microbiology Department, Clínica Universidad de Navarra, Pamplona, Spain.
(8) Instituto de Agrobiotecnología, CSIC-Universidad Pública Navarra-Gobierno Navarra, Mutilva, Spain Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
Nontypeable Haemophilus influenzae (NTHI) is an opportunistic pathogen that is an important cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). COPD is an inflammatory disease of the airways, and exacerbations are acute inflammatory events superimposed on this background of chronic inflammation.
Azithromycin (AZM) is a macrolide antibiotic with antibacterial and anti-inflammatory properties and a clinically proven potential for AECOPD prevention and management. Relationships between AZM efficacy and resistance by NTHI and between bactericidal and immunomodulatory effects on NTHI respiratory infection have not been addressed. In this study, we employed two pathogenic NTHI strains with different AZM susceptibilities (NTHI 375 [AZM susceptible] and NTHI 353 [AZM resistant]) to evaluate the prophylactic and therapeutic effects of AZM on the NTHI-host interplay.
At the cellular level, AZM was bactericidal toward intracellular NTHI inside alveolar and bronchial epithelia and alveolar macrophages, and it enhanced NTHI phagocytosis by the latter cell type. These effects correlated with the strain MIC of AZM and the antibiotic dose. Additionally, the effect of AZM on NTHI infection was assessed in a mouse model of pulmonary infection.
AZM showed both preventive and therapeutic efficacies by lowering NTHI 375 bacterial counts in lungs and bronchoalveolar lavage fluid (BALF) and by reducing histopathological inflammatory lesions in the upper and lower airways of mice. Conversely, AZM did not reduce bacterial loads in animals infected with NTHI 353, in which case a milder anti-inflammatory effect was also observed.
Together, the results of this work link the bactericidal and anti-inflammatory effects of AZM and frame the efficacy of this antibiotic against NTHI respiratory infection.
CITATION Antimicrob Agents Chemother. 2015 May;59(5):2700-12. doi: 10.1128/AAC.04447-14. Epub 2015 Feb 23.