Modulation of the activity of @entity3477 and XXXX in an in vitro pharmacodynamic model of @entity328 naive and induced biofilms.

@entity1 @entity3617 @entity689 @entity3167 @entity3477 @entity685 @entity13265 @entity3045 @entity30367 @entity71543 @entity328
OBJECTIVES: Bacterial biofilms developing in the bronchial tree of @entity1 experiencing acute exacerbations of chronic @entity3617 (AECBs) are suggested to cause relapses and recurrences of the disease because the matrix barrier impairs antibiotic access to the offending organisms. We examined whether bronchodilators could modulate pneumococcal biofilm development and antibiotic action using an in vitro model. METHODS: @entity328 strains from @entity1 hospitalized for AECBs and two reference strains (ATCC 49619 and R6) were screened for biofilm formation (multi-well plates; 2-11 days of growth). @entity13265 and @entity3045 (alone or in combination) were added at concentrations of 1.45 and 7.25 mg/L, respectively (mimicking those in the bronchial tree), and their effects were measured on biofilm formation and modulation of the activity of antibiotics [full antibiotic concentration-dependent effects (pharmacodynamic model)] with a focus on @entity3477 and @entity71543 . Bacterial viability and biomass were measured by the reduction of @entity30367 and crystal violet staining, respectively. Release of @entity3167 (from biofilm) and @entity689 activity were measured using enzymatic and HPLC-MS detection of @entity3167 . RESULTS: All clinical isolates produced biofilms, but with fast disassembly if from @entity1 who had received muscarinic antagonists. @entity13265 caused: (i) reduced biomass formation and faster biofilm disassembly with free @entity3167 release; and (ii) a marked improvement of antibiotic activity (bacterial killing and biomass reduction). @entity3045 stimulated @entity689 activity associated with improved antibiotic killing activity (reversed by @entity685 ) but modest biomass reduction. CONCLUSIONS: @entity13265 and, to a lesser extent, @entity3045 may cooperate with antibiotics for bacterial clearance and disassembly of pneumococcal biofilms.
