Two-month ciprofloxacin implants for multibacterial bone infections.

A ciprofloxacin implant formulation composed of 12% hydroxyapatite, 36% tricalcium phosphate, 12% poly(DL-lactide) (PLA) and 40% ciprofloxacin was characterized in vivo for use in treatment of multibacterial bone infection. After the implant was inserted in the femur of rabbits, approximately 90% of the total ciprofloxacin was released within 8 weeks, maintaining therapeutic levels in the femur and tibia. Throughout the femoral cortex and marrow these remained higher than the minimum inhibitory concentrations (MIC) against the most common pathogens causing osteomyelitis. Levels in tibia cortex were also above MIC for 6 weeks. The implant was characterized in terms of polymer degradation and morphological and crystallographic changes. X-ray analyses confirmed the osteoconductivity and biocompatibility of these materials. The sequential changes in the femur were those of a normal surgical trauma reaction followed by a repair process. All the results confirmed that ciprofloxacin release is limited by its low solubility, and that implant erosion and bone ingrowth into the implants enhance the antibiotic release.