RESUMO
Growth of members of most of the studied genera of gram-positive (Dietzia, Kocuria, and Rhodo- coccus) and gram-negative bacteria (Pseudomonas and Chromobacterium) in biofilms exhibited higher resistance to an translation inhibitor, azithromycin compared to the growth of planktonic cultures of the same strains. Low concentrations of azithromycin were found to stimulate biofilm formation by the studied saprotrophic strains. The rate of synthesis of the polysaccharide matrix component exceeded the rate of cell growth, indicating implementation of the biofilm phenotype under these conditions. It was found that an alkylhydroxybenzene (AHB) compound 4-hexylresorcinol was capable of almost uniform suppression of growth of both planktonic cultures and biofilms of the saprotrophic strains under study. In some cases, combined action ofazithromycin and AHB resulted in an additive inhibitory effect and prevented the stimulation of biofilm growth by subinhibitory azithromycin concentrations. Thus, AHB may be considered a promising antibiofilm agent.
Assuntos
Actinomycetales/efeitos dos fármacos , Azitromicina/farmacologia , Biofilmes/efeitos dos fármacos , Hexilresorcinol/farmacologia , Micrococcaceae/efeitos dos fármacos , Rhodococcus equi/efeitos dos fármacos , Actinomycetales/fisiologia , Antibacterianos/farmacologia , Azitromicina/antagonistas & inibidores , Biofilmes/crescimento & desenvolvimento , Chromobacterium/efeitos dos fármacos , Chromobacterium/fisiologia , Combinação de Medicamentos , Micrococcaceae/fisiologia , Plâncton/efeitos dos fármacos , Plâncton/crescimento & desenvolvimento , Polissacarídeos Bacterianos/agonistas , Polissacarídeos Bacterianos/antagonistas & inibidores , Polissacarídeos Bacterianos/biossíntese , Pseudomonas/efeitos dos fármacos , Pseudomonas/fisiologia , Rhodococcus equi/fisiologiaRESUMO
14-membered ring macrolides have been reported to have anti-inflammatory effects and to decrease neutrophil infiltration into the airways in chronic lower respiratory tract diseases. This study investigated the potential inhibitory effects of macrolide antibiotics on bleomycin-induced acute lung injury. Four drugs were studied: two 14-membered ring macrolides, clarithromycin (CAM) and roxithromycin (RXM); a 15-membered ring macrolide, azithromycin (AZM); and a 16-membered ring macrolide, josamycin (JM). Their effects were compared with macrolide untreated, pretreated, and post-treated groups. An acute lung injury was inhibited by pretreatment with CAM or RXM, which significantly ameliorated the bleomycin-induced increases in the total cell and neutrophil counts in bronchoalveolar lavage (BAL) fluids and the wet lung weight. The pretreatment with CAM or RXM also suppressed inflammatory cell infiltration and interstitial lung edema in the histopathological study. These inhibitory effects were associated with a decreased KC concentration in the BAL fluid and a decreased number of apoptotic cells in the lungs. Posttreatment with CAM or RXM had no marked inhibitory effects. Pretreatment with AZM was much less effective, and JM showed no inhibitory effects. These findings suggest that 14-membered ring macrolides have different effects on inflammatory lung disease than 15- and 16-membered ring macrolides and may be therapeutic agents for acute lung injury and pulmonary fibrosis.