Relationship between azithromycin susceptibility and administration efficacy for nontypeable Haemophilus influenzae respiratory infection
Fecha
2015Autor
Versión
Acceso abierto / Sarbide irekia
Tipo
Artículo / Artikulua
Versión
Versión publicada / Argitaratu den bertsioa
Impacto
|
10.1128/aac.04447-14
Resumen
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 ant ...
[++]
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 antiinflammatory
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. [--]
Materias
Azithromycin,
Nontypeable Haemophilus influenzae
Editor
American Society for Microbiology
Publicado en
Antimicrobial Agents and Chemotherapy, 59:2700 –2712
Departamento
Universidad Pública de Navarra/Nafarroako Unibertsitate Publikoa. IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua
Versión del editor
Entidades Financiadoras
J.M. was funded by Ph.D. studentship BES-2013-062644 from the Ministerio de Economía y Competitividad (MINECO), Spain. This work was
funded by grants from MINECO (grant SAF2012-31166) and the Departamento
Salud Gobierno Navarra (grant 359/2012) to J.G.