000032162 001__ 32162
000032162 005__ 20210121082859.0
000032162 0247_ $$2doi$$a10.1128/AAC.04447-14
000032162 0248_ $$2sideral$$a90846
000032162 037__ $$aART-2015-90846
000032162 041__ $$aeng
000032162 100__ $$aEuba, B.
000032162 245__ $$aRelationship between azithromycin susceptibility and administration efficacy for nontypeable Haemophilus influenzae respiratory infection
000032162 260__ $$c2015
000032162 5060_ $$aAccess copy available to the general public$$fUnrestricted
000032162 5203_ $$aNontypeable 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 sus- ceptibilities (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.
000032162 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/SAF2012-31166$$9info:eu-repo/grantAgreement/ES/MINECO/BES-2013-062644
000032162 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000032162 590__ $$a4.415$$b2015
000032162 591__ $$aPHARMACOLOGY & PHARMACY$$b34 / 255 = 0.133$$c2015$$dQ1$$eT1
000032162 591__ $$aMICROBIOLOGY$$b22 / 123 = 0.179$$c2015$$dQ1$$eT1
000032162 592__ $$a2.343$$b2015
000032162 593__ $$aInfectious Diseases$$c2015$$dQ1
000032162 593__ $$aPharmacology (medical)$$c2015$$dQ1
000032162 593__ $$aPharmacology$$c2015$$dQ1
000032162 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000032162 700__ $$aMoleres, J.
000032162 700__ $$aViadas, C.
000032162 700__ $$0(orcid)0000-0002-5225-661X$$aBarberán, M.$$uUniversidad de Zaragoza
000032162 700__ $$aCaballero, L.
000032162 700__ $$aGrilló, M.J
000032162 700__ $$aBengoechea, J.A.
000032162 700__ $$aDe-Torres, J.
000032162 700__ $$aLiñares, J.
000032162 700__ $$aLeiva, J.
000032162 700__ $$aGarmendia, J.
000032162 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal
000032162 773__ $$g59, 5 (2015), 2700-2712$$pAntimicrob. agents chemother.$$tAntimicrobial Agents and Chemotherapy$$x0066-4804
000032162 8564_ $$s1132033$$uhttps://zaguan.unizar.es/record/32162/files/texto_completo.pdf$$yVersión publicada
000032162 8564_ $$s135431$$uhttps://zaguan.unizar.es/record/32162/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000032162 909CO $$ooai:zaguan.unizar.es:32162$$particulos$$pdriver
000032162 951__ $$a2021-01-21-08:14:38
000032162 980__ $$aARTICLE