title: Prevention of Staphylococcus aureus biofilm formation by antibiotics in 96-Microtiter Well Plates and Drip Flow Reactors: critical factors influencing outcomes.
abstract: Biofilm formation leads to the failure of antimicrobial therapy. Thus, biofilm prevention is a desirable goal of antimicrobial research. In this study, the efficacy of antibiotics (doxycycline, oxacillin and rifampicin) in preventing Staphylococcus aureus biofilms was investigated using Microtiter Well Plates (MWP) and Drip Flow Reactors (DFR), two models characterized by the absence and the presence of a continuous flow of nutrients, respectively. Planktonic culture of S. aureus was exposed to antibiotics for one hour followed by 24 hours incubation with fresh nutrients in MWP or continuous flow of nutrients in DFR. The DFR grown biofilms were significantly more tolerant to the antibiotics than those grown in MWP without the continuous flow. The differences in log reductions (LR) between the two models could not be attributed to differences in the cell density, the planktonic inoculum concentration or the surface-area-to-volume ratios. However, eliminating the flow in the DFR significantly restored the antibiotic susceptibility. These findings demonstrate the importance of considering differences between experimental conditions in different model systems, particularly the flow of nutrients, when performing anti-biofilm efficacy evaluations. Biofilm antibiotic efficacy studies should be assessed using various models and more importantly, in a model mimicking conditions of its clinical application.
authors.affiliation: Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Abo Akademi University, BioCity, Artillerigatan 6A, FI-20520, Turku, Finland.
authors.forename: Suvi
authors.initials: S
authors.lastname: Manner
authors.affiliation: Center for Biofilm Engineering, Montana State University, Bozeman, MT 59717, USA.
authors.forename: Darla M
authors.initials: DM
authors.lastname: Goeres
authors.affiliation: Pharmaceutical Design and Discovery (PharmDD), Pharmaceutical Biology, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, P.O. Box 56, FI-00014 University of Helsinki, Finland.
authors.forename: Malena
authors.initials: M
authors.lastname: Skogman
authors.affiliation: Pharmaceutical Design and Discovery (PharmDD), Pharmaceutical Biology, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, P.O. Box 56, FI-00014 University of Helsinki, Finland.
authors.forename: Pia
authors.initials: P
authors.lastname: Vuorela
authors.affiliation: Pharmaceutical Design and Discovery (PharmDD), Pharmaceutical Biology, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, P.O. Box 56, FI-00014 University of Helsinki, Finland.
authors.forename: Adyary
authors.initials: A
authors.lastname: Fallarero
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001431:Bacteriological Techniques / Q000295:instrumentation / Q000379:methods*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D004318:Doxycycline / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D010068:Oxacillin / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000382:microbiology / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D004318:Doxycycline; D010068:Oxacillin; D012293:Rifampin