1. Antimicrob Agents Chemother. 2014 Nov;58(11):6385-97. doi: 10.1128/AAC.03482-14. 
Epub 2014 Aug 11.

Comparison of the Antibiotic Activities of Daptomycin, Vancomycin, and the
Investigational Fluoroquinolone Delafloxacin against Biofilms from Staphylococcus
aureus Clinical Isolates.

Siala W(1), Mingeot-Leclercq MP(1), Tulkens PM(1), Hallin M(2), Denis O(2), Van
Bambeke F(3).

Author information: 
(1)Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute,
Université Catholique de Louvain, Brussels, Belgium.
(2)Laboratoire de Microbiologie et Centre de Référence Belge des Staphylocoques,
Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
(3)Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute,
Université Catholique de Louvain, Brussels, Belgium

Biofilm-related infections remain a scourge. In an in vitro model of biofilms
using Staphylococcus aureus reference strains, delafloxacin and daptomycin were
found to be the most active among the antibiotics from 8 different
pharmacological classes (J. Bauer, W. Siala, P. M. Tulkens, and F. Van Bambeke,
Antimicrob. Agents Chemother. 57:2726-2737, 2013, doi:10.1128/AAC.00181-13). In
this study, we compared delafloxacin to daptomycin and vancomycin using biofilms 
produced by 7 clinical strains (S. aureus epidemic clones CC5 and CC8) in order
to rationalize the differences observed between the antibiotics and strains. The 
effects of the antibiotics on bacterial viability (resazurin reduction assay) and
biomass (crystal violet staining) were measured and correlated with the
proportion of polysaccharides in the matrix, the local microenvironmental pH
(micro-pH), and the antibiotic penetration in the biofilm. At clinically
meaningful concentrations, delafloxacin, daptomycin, and vancomycin caused a ≥25%
reduction in viability against the biofilms formed by 5, 4, and 3 strains,
respectively. The antibiotic penetration within the biofilms ranged from 0.6 to
52% for delafloxacin, 0.2 to 10% for daptomycin, and 0.2 to 1% for vancomycin;
for delafloxacin, this was inversely related to the polysaccharide proportion in 
the matrix. Six biofilms were acidic, explaining the high potency of delafloxacin
(lower MICs at acidic pH). Norspermidine and norspermine (disassembling the
biofilm matrix) drastically increased delafloxacin potency and efficacy (50%
reduction in viability for 6 biofilms at clinically meaningful concentrations) in
direct correlation with its increased penetration within the biofilm, while they 
only modestly improved daptomycin efficacy (50% reduction in viability for 2
biofilms) and penetration, and they showed marginal effects with vancomycin.
Delafloxacin potency and efficacy against biofilms are benefited by its
penetration into the matrix and the local acidic micro-pH.

Copyright © 2014, American Society for Microbiology. All Rights Reserved.

PMID: 25114142  [PubMed - in process]