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

Osteomyelitis (OM) frommultidrug-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 availible in bone void fillers for local high-dose delivery. To address this, we developed amousemodel with MDR strains isolated from wounded military personnel. In contrast to S. aureus OM, which is osteolytic and characterized by biofilmin 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.PCRfor the A. baumannii-specific parCgene 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 colistin methate 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 themice had detectable levels of parC at 19 days (p < 0.05 vs. i.m. colistin and placebo).