1. Antimicrob Agents Chemother. 2013 Jun;57(6):2726-37. doi: 10.1128/AAC.00181-13.
Epub 2013 Apr 9.

A Combined Pharmacodynamic Quantitative and Qualitative Model Reveals the Potent 
Activity of Daptomycin and Delafloxacin against Staphylococcus aureus Biofilms.

Bauer J, Siala W, Tulkens PM, Van Bambeke F.

Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute,
Université catholique de Louvain, Brussels, Belgium.

Biofilms are associated with persistence of Staphylococcus aureus infections and 
therapeutic failures. Our aim was to set up a pharmacodynamic model comparing
antibiotic activities against biofilms and examining in parallel their effects on
viability and biofilm mass. Biofilms of S. aureus ATCC 25923
(methicillin-sensitive S. aureus [MSSA]) or ATCC 33591 (methicillin-resistant S. 
aureus [MRSA]) were obtained by culture in 96-well plates for 6 h/24 h.
Antibiotic activities were assessed after 24/48 h of exposure to concentrations
ranging from 0.5 to 512 times the MIC. Biofilm mass and bacterial viability were 
quantified using crystal violet and the redox indicator resazurin. Biofilms
stained with Live/Dead probes were observed by using confocal microscopy.
Concentration-effect curves fitted sigmoidal regressions, with a 50% reduction
toward both matrix and viability obtained at sub-MIC or low multiples of MICs
against young biofilms for all antibiotics tested. Against mature biofilms,
maximal efficacies and potencies were reduced, with none of the antibiotics being
able to completely destroy the matrix. Delafloxacin and daptomycin were the most 
potent, reducing viability by more than 50% at clinically achievable
concentrations against both strains, as well as reducing biofilm depth, as
observed in confocal microscopy. Rifampin, tigecycline, and moxifloxacin were
effective against mature MRSA biofilms, while oxacillin demonstrated activity
against MSSA. Fusidic acid, vancomycin, and linezolid were less potent overall.
Antibiotic activity depends on biofilm maturity and bacterial strain. The
pharmacodynamic model developed allows ranking of antibiotics with respect to
efficacy and potency at clinically achievable concentrations and highlights the
potential utility of daptomycin and delafloxacin for the treatment of
biofilm-related infections.

PMID: 23571532  [PubMed - in process]