title: Therapy of intracellular Staphylococcus aureus by tigecyclin.
abstract: BACKGROUND
  In the fields of traumatology and orthopaedics staphylococci are the most frequently isolated pathogens. Staphylococcus aureus and Staphylococcus epidermidis are known to be the major causative agents of osteomyelitis. The increasing number of multiresistant Staphylococcus aureus and resistant coagulase-negative staphylococci as a trigger of complicated osteomyelitis and implant-associated infections is a major problem. Antibiotic therapy fails in 20% of cases. Therefore the development of novel antibiotics becomes necessary.
  
  
  METHODS
  This study analyses tigecyclin, the first antibiotic of the glycylines, as a potential therapy for osteomyelitis caused by multiresistant Staphylococcus aureus. Therefore its intracellular activity and the potential use in polymethylmetacrylate-bone cement are examined. The intracellular activity of tigecyclin is determined by a human osteoblast infection model. The investigation of the biomechanical characteristics is conducted concerning the ISO 5833-guidelines.
  
  
  RESULTS
  Tigecyclin shows in vitro an intracellular activity that ranges between the antimicrobial activity of gentamicin and rifampicin. A significant negative effect on the biomechanical characteristics with an impaired stability is detected after adding tigecyclin to polymethylmetacrylate-bone cement with a percentage of 1.225% per weight.
  
  
  CONCLUSIONS
  This study shows that tigecyclin might be a potent alternative for the systemic therapy of osteomyelitis and implant-associated infections whereas the local application has to be reconsidered individually.
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Hospital of Muenster, Waldeyerstr. 1, 48149, Muenster, Germany. Carolin.Kreis@ukmuenster.de
authors.forename: Carolin A
authors.initials: CA
authors.lastname: Kreis
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Raschke
authors.forename: Steffen B
authors.initials: SB
authors.lastname: Roßlenbroich
authors.forename: Nancy
authors.initials: N
authors.lastname: Tholema-Hans
authors.forename: Bettina
authors.initials: B
authors.lastname: Löffler
authors.forename: Thomas
authors.initials: T
authors.lastname: Fuchs
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001696:Biomechanical Phenomena; D001843:Bone Cements / Q000737:chemistry*; D002478:Cells, Cultured; D006801:Humans; D042541:Intracellular Space / Q000382:microbiology*; D008422:Materials Testing; D008911:Minocycline / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D008954:Models, Biological; D010006:Osteoblasts / Q000378:metabolism / Q000382:microbiology; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology; D016459:Prosthesis-Related Infections; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects*; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D001843:Bone Cements; D000078304:Tigecycline; D008911:Minocycline