Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Jiaotong University, 600 Yishan Road, 200233 Shanghai, China.
Antimicrob Agents Chemother. 2010 Jan;54(1):170-6. doi: 10.1128/AAC.01122-09. Epub 2009 Nov 16.
The in vitro and in vivo therapeutic efficacies of teicoplanin-loaded calcium sulfate (TCS; 10% [wt] teicoplanin) were investigated in a rabbit model of chronic methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. The in vitro elution characteristics of teicoplanin from TCS pellets were realized by carrying out an evaluation of the release kinetics, recovery rate, and antibacterial activity of the released teicoplanin. Chronic osteomyelitis was induced by inoculating 10(7) CFU of a MRSA strain into the tibial cavity of rabbits. After 3 weeks, the animals were treated by debridement followed by implantation of TCS pellets in group 1, calcium sulfate (CS) pellets alone in group 2, and intravenous (i.v.) teicoplanin (6 mg/kg of body weight every 12 h for three doses and then every 24 h up to 4 weeks) in group 3. Animals in group 4 were left untreated. After 6 weeks, the efficacy of the osteomyelitis treatment was evaluated by hematological, radiological, microbiological, and histological examinations. In vitro elution studies showed sustained release of teicoplanin at a therapeutic level over a time period of 3 weeks. The released teicoplanin maintained its antibacterial activity. In vivo, the best therapeutic effect was observed in animals treated with TCS pellets, resulting in significantly lower radiological and histological scores, lower positive rates of MRSA culture and bacterial load, and excellent bone regeneration compared with those treated by CS alone or i.v. teicoplanin, without any local or systemic adverse effects. TCS pellets are an effective alternative to i.v. teicoplanin for the treatment of chronic MRSA osteomyelitis, particularly because teicoplanin is delivered locally while the TCS pellets simultaneously promote bone defect repair.
研究了载硫酸钙（TCS；10％[wt]替考拉宁）替考拉宁治疗兔慢性耐甲氧西林金黄色葡萄球菌（MRSA）骨髓炎的体内外疗效。通过评估替考拉宁从 TCS 丸中的释放动力学、回收率和释放的替考拉宁的抗菌活性，实现了替考拉宁从 TCS 丸中的体外洗脱特性。通过将 10（7）CFU 的 MRSA 菌株接种到兔胫骨腔中，诱导慢性骨髓炎。3 周后，通过清创术对动物进行治疗，然后在第 1 组中植入 TCS 丸，第 2 组中单独植入硫酸钙（CS）丸，第 3 组中静脉内（i.v.）替考拉宁（6mg/kg 体重，每 12 小时一次，连续 3 次，然后每 24 小时一次，持续 4 周），第 4 组未治疗。6 周后，通过血液学、影像学、微生物学和组织学检查评估骨髓炎治疗的疗效。体外洗脱研究表明，替考拉宁在 3 周的时间内以治疗水平持续释放。释放的替考拉宁保持其抗菌活性。在体内，用 TCS 丸治疗的动物观察到最佳的治疗效果，与单独用 CS 或 i.v.替考拉宁治疗的动物相比，其影像学和组织学评分明显较低，MRSA 培养和细菌负荷的阳性率较低，骨再生良好，且无局部或全身不良反应。TCS 丸是治疗慢性 MRSA 骨髓炎的静脉内替考拉宁的有效替代品，特别是因为替考拉宁局部给药，而 TCS 丸同时促进骨缺损修复。
