title: Tetracycline delivery from fibrin controls peritoneal infection without measurable systemic antibiotic.
abstract: The addition of antibiotics to an adhesive haemostat results in an ideal system for the treatment of a localized infectious disease. Fibrin sealant (FS) is a biocompatible, resorbable, adherent haemostat that can deliver antibiotics. Previous use of fibrin to deliver antibiotics resulted in rapid release and limited bioactivity. We have reported previously that poorly soluble antibiotics significantly retard release from FS, resulting in extended delivery in vitro, and overcome antibiotic-resistant infection. We now report that localized antibiotic delivery from FS controls peritoneal infection without measurable systemic antibiotic. Rats and mice were implanted with preformed FS discs containing tetracycline free-base to evaluate control of peritoneal sepsis and to measure serum tetracycline levels. Infection was initiated with Staphylococcus aureus. Morbidity and mortality were evaluated for 14 days. Serum was isolated from jugular vein blood with subsequent evaluation for antimicrobial activity. Mice prophylactically treated with FS-tetracycline (FS-TET) 500 mg/kg 2 days before infection cleared the S. aureus infection, resulting in 100% survival. Mice treated with FS-TET 500 mg/kg 7 days before infection survived. Mice treated with FS-TET 1750 mg/kg 35 days before infection also survived. Rats treated with FS-TET 500 mg/kg had undetectable serum tetracycline levels, whereas in vitro release of tetracycline from FS-TET pellets in rat serum was readily detected. We conclude that fibrin is an excellent vehicle for extended delivery of low solubility tetracycline. Tetracycline delivered from FS is an appropriate chemotherapy for S. aureus peritonitis. FS-TET controls localized infection without a measurable concentration of systemic tetracycline.
authors.affiliation: Department of Biological Sciences, Kent State University, Kent, OH 44242, USA. cwoolver@kent.edu
authors.forename: C J
authors.initials: CJ
authors.lastname: Woolverton
authors.forename: J A
authors.initials: JA
authors.lastname: Fulton
authors.forename: S J
authors.initials: SJ
authors.lastname: Salstrom
authors.forename: J
authors.initials: J
authors.lastname: Hayslip
authors.forename: N A
authors.initials: NA
authors.lastname: Haller
authors.forename: M L
authors.initials: ML
authors.lastname: Wildroudt
authors.forename: M
authors.initials: M
authors.lastname: MacPhee
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D015718:Fibrin Tissue Adhesive / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D010538:Peritonitis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000473:pathology; D013752:Tetracycline / Q000008:administration & dosage*; D014014:Tissue Adhesives / Q000008:administration & dosage*
chemical_list: D000900:Anti-Bacterial Agents; D015718:Fibrin Tissue Adhesive; D014014:Tissue Adhesives; D013752:Tetracycline