Ceftazidime Cationic Liposome Combined With Nano-hydroxyapatite/β-tricalcium Phosphate For Treatment Of Chronic Osteomyelitis Of Rabbits

Objective:To observe the effect of cationic liposomal ceftazidime (CLC) combined with nano-hydroxyapatite/β-tricalcium phosphate (n-HA/B-TC) in the treatment of chronic osteomyelitis of rabbits.Methods:1. The establishment of chronic osteomyelitis induces by staphylococcus aureus in rabbit’s tibia Thirty healthy New Zealand white rabbits were drilled by5mm bone drilling in the proximal of the tibia under general anaesthesia by sodium pentobarbital for the bone defects. All rabbits were injected5ul sodium morrhuate (as the sclerosing agents) and staphylococcus aureus (2×106cfu in total) into the proximal tibial marrow cavity, without any treatment after bone wax. Evaluation was done by clinical, radiologic, bacteriologic and histopathology after four weeks.Ceftazidime cationic liposome combined with nano-hydroxyapatite/B-tricalcium phosphate for treatment of chronic osteomyelitis of rabbits Thirty healthy New Zealand white rabbits were selected to prepare for the chronic osteomyelitis models. After two weeks, the observations of gross and X-ray were done and there were27models were made successfully.24rabbits in the27models were randomly divided into four groups (n=6):group A were treated with debridement only, group B were treated with ceftazidime (90mg/Kg, bid, for2weeks) after the debridement, group C were treated with ceftazidime and n-HA/β-TC after the debridement, and group D were treated with CLCs and n-HA/B-TCP. Norden scores of the X-ray、 GBPS scores、 Smeltzer scores、 positive rate of bacteria culture of each group were observed and compared. Results:1. There was clinical progression of the disease observed by draining wounds, the early wound pyorrhea, local inflammatory edema, a postoperative limp that survived in all rabbits, and varied degrees of anorexia with weight loss in all rabbits. There were3cases dead for fatal sepsis at early period. Twenty-seven of the30animals had radiographic evidence of osteomyelitis. Radiologic features were moderate to typical osteomyelitis, moderate to extensive periosteal reaction, cortical lysis, mild to extensive new bone formation and frequent development of sequestra limited to the proximal part of the tibia. All specimens were cultured staphylococcus aureus. Histopathology showed chronic active inflammation, osteolysis, new woven bone formation. This method can successfully prepare animal models of chronic osteomyelitis with an achievement ratio of90.0%(27/30).2. At4weeks after modeling, the Norden scores of the X-ray of all rabbits were over3,3.75±0.63on average. There were no significant differences in the Norden scores in the4groups (P>0.05). At8weeks after treatment, sinus healed in group C and D, but sinus was observed in groups A and B; the GBPS scores of group C and D were significantly lower than group A and B (P<0.05); the Norden scores of group D was significantly lower than group A, B and C (P<0.05); the Smeltzer scores of group C and D were significantly lower than group A and B (P<0.05); the positive rate of bacteria culture of group D was significantly lower than group A, B and C (P<0.05).Conclusion:1. This method could establish the animal models in rabbits’tibia of chronic osteomyelitis efficiently with satisfaction and was deserved to be used in the research of the animal of chronic osteomyelitis widely.2. Cationic liposomal ceftazidime and n-HA/B-TCP had good effect in treating chronic osteomyelitis of rabbits. This treatment was deserved further study and it was expected to be used in clinical application.