GLYCOPEPTIDES, FLUOROQUINOLONES AND CARBAPENEMS DIFFUSION IN PSEUDOARTHROSIC INFECTED BONE

The management of post-traumatic bone infections relies on antibiotic therapy and surgical debridement. Antibiotic concentration in infected bone is a major determinant of response to medical treatment. The aim is to assess glycopeptides, fluoroquinolones and carbapenems diffusion in infected human bone, since they are widely used for treating bone infections. Twenty-four patients with septic pseudoarthrosis undergoing surgical debridement and treated with glycopeptides/fluoroquinolones/carbapenems iv for >1 week were studied. Plasma and bone specimens were collected intraoperatively at a mean of 4.8h after antibiotic administration. Antibiotic concentrations were measured by the HPLC-UV method. Five patients received vancomycin: mean bone concentrations were 2.4mg/L in cortical and 7.1mg/L in cancellous bone, with a bone/plasma extraction of 12% and 36%, respectively. Nine patients were treated with teicoplanin: bone concentrations were 2.5mg/L for cortical and 8.3mg/L for cancellous bone (14% and 46% of plasma levels). Five patients received a fluoroquinolone. Ciprofloxacin concentrations were 1.8mg/L in cortical bone and 30.2mg/L in cancellous and newly formed bone (respective bone/plasma ratios 1.06 and 8.4). Levofloxacin concentrations were 0.3 and 2.69mg/L in cortical and cancellous bone, with diffusion rates of 12% and 108%, respectively. Five patients received a carbapenem. Imipenem diffusion rates were respectively 7.5% and 58.3% for cortical and cancellous bone (bone concentrations 0.09 mg/L and 0.7 mg/L). Meropenem levels were 1.2 mg/L and 5.2 mg/L in cortical and cancellous bone, with respective diffusion rates of 3.6% and 15%. Both glycopeptides provided concentrations exceeding the MIC of infecting agents, with satisfactory bone diffusion. Fluoroquinolones, especially ciprofloxacin, displayed excellent diffusion. Ciprofloxacin concentrations in cancellous and new bone were far higher than in plasma, suggesting accumulation into highly vascularized tissue. Imipenem had better diffusion than meropenem, but bone levels were under the MIC of susceptible agents. Glicopeptides and fluoroquinolones appear excellent options for bone infections, while carbapenems should be a second choice treatment.