title: Prevention of biofilm formation by methacrylate-based copolymer films loaded with rifampin, clarithromycin, doxycycline alone or in combination.
abstract: OBJECTIVE
  This study reports the incorporation of the antibiotics rifampin, doxycycline and clarithromycin in poly(styrene-co-methyl methacrylate films and their effect on biofilm prevention.
  
  
  BACKGROUND
  Invasive procedures in patients such as surgical device, or intravenous or urinary catheter implantation, often results in complicated hospital-acquired nosocomial infections. Biofilm formation is essential to establish these infections on these devices and novel antibiotic delivery approaches are needed for more effective management.
  
  
  METHODS
  The films were evaluated in vitro for drug release and for their ability to prevent biofilm formation by methicillin susceptible and methicillin resistant Staphylococcus aureus. Surface tension components, obtained from contact angle measurements, and the morphology of the films evaluated by scanning electron microscopy were also investigated.
  
  
  RESULTS
  In this study, antibiotic-loaded methacrylic copolymer films that effectively released rifampin, clarithromycin and doxycycline for up to 21 days prevented biofilm formation when tested in an in vitro bioreactor model. These drug loaded copolymer films provided the advantage by coating materials with a novel surface that was unsuitable for resettling of biofilms once the antibiotic was dissolved from the polymer surface. A combination of rifampin and clarithromycin released from the polymer film provided >99.9% kill of an MRSA inoculate for up to 72 h.
  
  
  CONCLUSIONS
  Results showed that combining multiple drugs in copolymer films with unique surface properties, initial hydrophilicity and increase in roughness, can be an effective way to prevent biofilm formation.
authors.affiliation: School of Pharmacy, University of Wisconsin, 777 Highland Avenue, Madison, Wisconsin, 53705-2222, USA.
authors.forename: Warren E
authors.initials: WE
authors.lastname: Rose
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Otto
authors.forename: Marique E
authors.initials: ME
authors.lastname: Aucamp
authors.forename: Zach
authors.initials: Z
authors.lastname: Miller
authors.forename: Melgardt M
authors.initials: MM
authors.lastname: de Villiers
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D019149:Bioreactors / Q000382:microbiology; D017291:Clarithromycin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D004318:Doxycycline / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry*; D004338:Drug Combinations; D065546:Drug Liberation; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D019904:Polymethyl Methacrylate / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry*; D012293:Rifampin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013499:Surface Properties
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004338:Drug Combinations; D011137:Polystyrenes; C000600071:poly(styrene-co-methylmethacrylate); D019904:Polymethyl Methacrylate; D017291:Clarithromycin; D004318:Doxycycline; D012293:Rifampin