1. J Antimicrob Chemother. 2015 Jun;70(6):1713-26. doi: 10.1093/jac/dkv032. Epub
2015 Feb 23.

Modulation of the activity of moxifloxacin and solithromycin in an in vitro
pharmacodynamic model of Streptococcus pneumoniae naive and induced biofilms.

Vandevelde NM(1), Tulkens PM(1), Muccioli GG(2), Van Bambeke F(3).

Author information: 
(1)Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute,
Université catholique de Louvain, Brussels, Belgium. (2)Bioanalysis and
Pharmacology of Bioactive Lipids, Louvain Drug Research Institute, Université
catholique de Louvain, Brussels, Belgium. (3)Pharmacologie cellulaire et
moléculaire, Louvain Drug Research Institute, Université catholique de Louvain,
Brussels, Belgium francoise.vanbambeke@uclouvain.be.

OBJECTIVES: Bacterial biofilms developing in the bronchial tree of patients
experiencing acute exacerbations of chronic bronchitis (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: Streptococcus pneumoniae strains from patients hospitalized for AECBs
and two reference strains (ATCC 49619 and R6) were screened for biofilm formation
(multi-well plates; 2-11 days of growth). Ipratropium and salbutamol (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
moxifloxacin and solithromycin. Bacterial viability and biomass were measured by 
the reduction of resazurin and crystal violet staining, respectively. Release of 
sialic acid (from biofilm) and neuraminidase activity were measured using
enzymatic and HPLC-MS detection of sialic acid.
RESULTS: All clinical isolates produced biofilms, but with fast disassembly if
from patients who had received muscarinic antagonists. Ipratropium caused: (i)
reduced biomass formation and faster biofilm disassembly with free sialic acid
release; and (ii) a marked improvement of antibiotic activity (bacterial killing 
and biomass reduction). Salbutamol stimulated neuraminidase activity associated
with improved antibiotic killing activity (reversed by zanamivir) but modest
biomass reduction.
CONCLUSIONS: Ipratropium and, to a lesser extent, salbutamol may cooperate with
antibiotics for bacterial clearance and disassembly of pneumococcal biofilms.

© The Author 2015. Published by Oxford University Press on behalf of the British 
Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions,
please e-mail: journals.permissions@oup.com.

PMID: 25712316  [PubMed - in process]