title: Topical Minocycline Effectively Decontaminates and Reduces Inflammation in Infected Porcine Wounds.
abstract: BACKGROUND
  Wound infection can impair postoperative healing. Topical antibiotics have potential to treat wound infection and inflammation and minimize the adverse effects associated with systemic antibiotics.
  
  
  METHODS
  Full-thickness porcine wounds were infected with Staphylococcus aureus. Using polyurethane wound enclosure devices, wounds were treated with topical 100 μg/ml minocycline, topical 1000 μg/ml minocycline, topical saline control, or 4 mg/kg intravenous minocycline. Bacteria were quantified in wound tissue and fluid obtained over 9 hours. Immunosorbent assays were used to analyze inflammatory marker concentrations. Minocycline's effect on in vitro migration and proliferation of human keratinocytes and fibroblasts was tested using scratch assays and metabolic assays, respectively.
  
  
  RESULTS
  After 6 hours, 100 and 1000 μg/ml topical minocycline decreased bacteria in wound tissue to 3.5 ± 0.87 and 2.9 ± 2.3 log colony-forming units/g respectively, compared to 8.3 ± 0.9 log colony-forming units/g in control wounds (p < 0.001) and 6.9 ± 0.2 log colony-forming units/g in wounds treated with 4 mg/kg intravenous minocycline (p < 0.01). After 2 hours, topical minocycline reduced concentrations of the inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α (p < 0.01), and inflammatory cell counts in wound tissue (p < 0.05). In noninfected wounds, topical minocycline significantly reduced interleukin-1β, interleukin-6, and inflammatory cell counts after 4 hours (p < 0.01). Matrix metalloproteinase-9 concentrations decreased after 1-hour treatment (p < 0.05). Keratinocyte and fibroblast in vitro functions were not adversely affected by 10 μg/ml minocycline or less.
  
  
  CONCLUSIONS
  Topical minocycline significantly reduces bacterial burden and inflammation in infected wounds compared with wounds treated with intravenous minocycline or control wounds. Minocycline also decreases local inflammation independently of its antimicrobial effect.
authors: Boston, Mass.|From the Division of Plastic Surgery and the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School.
authors: Lauren Tracy
authors: LT
authors: Daly
authors: Boston, Mass.|From the Division of Plastic Surgery and the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School.
authors: David M
authors: DM
authors: Tsai
authors: Boston, Mass.|From the Division of Plastic Surgery and the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School.
authors: Mansher
authors: M
authors: Singh
authors: Boston, Mass.|From the Division of Plastic Surgery and the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School.
authors: Kristo
authors: K
authors: Nuutila
authors: Boston, Mass.|From the Division of Plastic Surgery and the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School.
authors: Raquel A
authors: RA
authors: Minasian
authors: Boston, Mass.|From the Division of Plastic Surgery and the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School.
authors: Cameron C Y
authors: CCY
authors: Lee
authors: Boston, Mass.|From the Division of Plastic Surgery and the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School.
authors: Elizabeth
authors: E
authors: Kiwanuka
authors: Boston, Mass.|From the Division of Plastic Surgery and the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School.
authors: Florian
authors: F
authors: Hackl
authors: Boston, Mass.|From the Division of Plastic Surgery and the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School.
authors: Andrew B
authors: AB
authors: Onderdonk
authors: Boston, Mass.|From the Division of Plastic Surgery and the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School.
authors: Johan P E
authors: JPE
authors: Junker
authors: Boston, Mass.|From the Division of Plastic Surgery and the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School.
authors: Elof
authors: E
authors: Eriksson
authors: Boston, Mass.|From the Division of Plastic Surgery and the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School.
authors: Edward J
authors: EJ
authors: Caterson
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D007275:Injections, Intravenous; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008911:Minocycline / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D013203:Staphylococcal Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D013552:Swine; D016896:Treatment Outcome; D014946:Wound Infection / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D008911:Minocycline