Relationship between azithromycin susceptibility and administration efficacy for nontypeable Haemophilus influenzae respiratory infection

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dc.contributor.authorEuba, Begoña
dc.contributor.authorMoleres Apilluelo, Javier
dc.contributor.authorViadas Martínez, Cristina
dc.contributor.authorBarberán, Montserrat
dc.contributor.authorCaballero Coronado, Lucía
dc.contributor.authorGrilló Dolset, María Jesús
dc.contributor.authorBengoechea Alonso, José Antonio
dc.contributor.authorTorres, Juan de
dc.contributor.authorLiñares, Josefina
dc.contributor.authorLeiva, José
dc.contributor.authorGarmendia García, Juncal
dc.contributor.departmentIdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutuaes_ES
dc.contributor.funderGobierno de Navarra / Nafarroako Gobernua, 359/2012es
dc.date.accessioned2019-01-10T08:27:51Z
dc.date.available2019-01-10T08:27:51Z
dc.date.issued2015
dc.description.abstractNontypeable 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.en
dc.description.sponsorshipJ.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.en
dc.format.extent13 p.
dc.format.mimetypeapplication/pdfen
dc.format.mimetypeapplication/zipen
dc.identifier.doi10.1128/aac.04447-14
dc.identifier.issn0066-4804 (Print)
dc.identifier.issn1098-6596 (Electronic)
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/31930
dc.language.isoengen
dc.publisherAmerican Society for Microbiologyen
dc.relation.ispartofAntimicrobial Agents and Chemotherapy, 59:2700 –2712en
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO//SAF2012-31166/ES/
dc.relation.publisherversionhttps://doi.org/10.1128/aac.04447-14
dc.rights© 2015, American Society for Microbiology. All Rights Reserved.en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.subjectAzithromycinen
dc.subjectNontypeable Haemophilus influenzaeen
dc.titleRelationship between azithromycin susceptibility and administration efficacy for nontypeable Haemophilus influenzae respiratory infectionen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublication0e8e1c09-428a-47b7-819c-7c372f0c7242
relation.isAuthorOfPublication6018a4d2-1ded-494f-92de-2ca4cebbe693
relation.isAuthorOfPublication.latestForDiscovery0e8e1c09-428a-47b7-819c-7c372f0c7242

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