title: Experimental osteomyelitis caused by methicillin-resistant Staphylococcus aureus treated with a polylactide carrier releasing linezolid.
abstract: BACKGROUND
  The effectiveness of a new delivery system consisting of polymerized dilactide (PLA) with incorporated linezolid was investigated in a rabbit model as a means of treating methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis.
  
  
  METHODS
  The PLA-linezolid system was prepared after thorough stirring of PLA with linezolid at a 10:1 ratio. Experimental osteomyelitis was established in 40 rabbits by a modification of the Norden model with MRSA as the test isolate. After a hole had been drilled in the upper right femur, the isolate was inoculated using a thin needle working as a foreign body. At three weeks, the needle was removed and cultured, and the PLA-linezolid system was implanted in half the animals (group B); the remaining half was the control group (group A). Animals were sacrificed at regular intervals; tissue around the site of implantation was examined for pathologic changes and cultured quantitatively.
  
  
  RESULTS
  The prepared system eluted linezolid in vitro at concentrations much greater than the minimum inhibitory concentration (MIC) of the test pathogen for 11 days. At three weeks after inoculation of the test isolate, all animals had osteomyelitis. By the sixth week, bacterial growth from cancellous bone of group B was significantly lower than that in group A. However, this effect was not maintained until the end of the study (weeks 8 and 10), when the differences in bacterial growth in the two groups were not significant.
  
  
  CONCLUSIONS
  Polymerized dilactide mixed with 10% linezolid achieved partial arrest of the offending pathogen in an experimental model of osteomyelitis caused by MRSA.
authors.affiliation: Second Department of Orthopaedics, University Medical School, Athens, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Tsiolis
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
authors.forename: Andreas F
authors.initials: AF
authors.lastname: Mavrogenis
authors.forename: Olga
authors.initials: O
authors.lastname: Savvidou
authors.forename: Stergios N
authors.initials: SN
authors.lastname: Lallos
authors.forename: Konstantina
authors.initials: K
authors.lastname: Frangia
authors.forename: Ioannis
authors.initials: I
authors.lastname: Lazarettos
authors.forename: Vassilios
authors.initials: V
authors.lastname: Nikolaou
authors.forename: Nikolaos E
authors.initials: NE
authors.lastname: Efstathopoulos
mesh_terms: D000081:Acetamides / Q000008:administration & dosage*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods; D000069349:Linezolid; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology; D023303:Oxazolidinones / Q000008:administration & dosage*; D011091:Polyesters / Q000008:administration & dosage*; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D023303:Oxazolidinones; D011091:Polyesters; C033616:poly(lactide); D000069349:Linezolid