Efficacy of colistin-impregnated beads to prevent multidrug-resistant A. baumannii implant-associated osteomyelitis.

Journal Article

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).

Full Text

Duke Authors

Cited Authors

  • Crane, DP; Gromov, K; Li, D; Søballe, K; Wahnes, C; Büchner, H; Hilton, MJ; O'Keefe, RJ; Murray, CK; Schwarz, EM

Published Date

  • August 2009

Published In

Volume / Issue

  • 27 / 8

Start / End Page

  • 1008 - 1015

PubMed ID

  • 19173261

Electronic International Standard Serial Number (EISSN)

  • 1554-527X

International Standard Serial Number (ISSN)

  • 0736-0266

Digital Object Identifier (DOI)

  • 10.1002/jor.20847

Language

  • eng