title: Efficacy of colistin-impregnated beads to prevent multidrug-resistant A. baumannii implant-associated osteomyelitis.
abstract: Osteomyelitis (OM) from multidrug-resistant (MDR) Acinetobacter has emerged in >30% of combat-related injuries in Iraq and Afghanistan. While most of these strains are sensitive to colistin, the drug is not available in bone void fillers for local high-dose delivery. To address this, we developed a mouse model with MDR strains isolated from wounded military personnel. In contrast to S. aureus OM, which is osteolytic and characterized by biofilm in necrotic bone, A. baumannii OM results in blastic lesions that do not contain apparent biofilm. We also found that mice mount a specific IgG response against three proteins (40, 47, and 56 kDa) regardless of the strain used, suggesting that these may be immuno-dominant antigens. PCR for the A. baumannii-specific parC gene confirmed a 100% infection rate with 75% of the MDR strains, and in vitro testing confirmed that all strains were sensitive to colistin. We also developed a real-time quantitative PCR (RTQ-PCR) assay that could detect as few as 10 copies of parC in a sample. To demonstrate the efficacy of colistin prophylaxis in this model, mice were treated with either parenteral colistin (0.2 mg colistinmethate i.m. for 7 days), local colistin (PMMA bead impregnated with 1.0 mg colistin sulfate), or an unloaded PMMA bead control. While the parenteral colistin failed to demonstrate any significant effects versus the placebo, the colistin PMMA bead significantly reduced the infection rate such that only 29.2% of the mice had detectable levels of parC at 19 days (p < 0.05 vs. i.m. colistin and placebo).
authors.affiliation: The Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, New York 14642, USA.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Crane
authors.forename: Kirill
authors.initials: K
authors.lastname: Gromov
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Kjeld
authors.initials: K
authors.lastname: Søballe
authors.forename: Christian
authors.initials: C
authors.lastname: Wahnes
authors.forename: Hubert
authors.initials: H
authors.lastname: Büchner
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hilton
authors.forename: Regis J
authors.initials: RJ
authors.lastname: O'Keefe
authors.forename: Clinton K
authors.initials: CK
authors.lastname: Murray
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schwarz
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000517:prevention & control; D040981:Acinetobacter baumannii / Q000187:drug effects / Q000235:genetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D003091:Colistin / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D005260:Female; D050723:Fractures, Bone / Q000150:complications; D051379:Mice; D008810:Mice, Inbred C57BL; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology / Q000517:prevention & control
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin