Koshiko Susumu, Sasajima Tadahiro, Muraki Senichi, Azuma Nobuyoshi, Yamazaki Kohsuke, Chiba Kaoru, Tachibana Mineji, Inaba Masashi
Department of Surgery, Asahikawa Medical University, Japan.
J Vasc Surg. 2002 Apr;35(4):779-85. doi: 10.1067/mva.2002.121850.
Efficacy and duration of antibacterial activity of rifampicin-gelatin grafts against virulent organisms were evaluated in an animal model.
Rifampicin-gelatin grafts were prepared with impregnation of Gelseal (Vascutek Ltd, Scotland) graft in 1 mg/mL rifampicin solution. Rifampicin-gelatin grafts (6 cm long; n = 24) and plain Gelseal grafts as controls (n = 4) were implanted into the canine abdominal aorta with inoculation of Staphylococcus epidermidis, Escherichia coli, or methicillin-resistant Staphylococcus aureus (MRSA), and the rifampicin-gelatin grafts were retrieved after 1 to 4 weeks. Disks cut from the retrieved rifampicin-gelatin grafts were placed on agar plates streaked with one of the organisms, and the graft antibacterial activity was assessed with the width of the inhibition zone.
In in vitro tests, initial inhibition zones (inhibition zone of 24 hours after incubation) of rifampicin-gelatin grafts against S epidermidis, MRSA, and E coli were 40.0 +/- 0.3 mm, 36.0 +/- 0.2 mm, and 11.8 +/- 0.1 mm, respectively. In the implantation, S epidermidis -inoculated rifampicin-gelatin grafts had no findings of graft infection, and no colony growth was recognized on the plates streaked with the perigraft fluids. Initial inhibition zones of S epidermidis -inoculated rifampicin-gelatin grafts retrieved at 1 or 2 weeks were 20.1 +/- 1.1 mm and 7.6 +/- 1.0 mm, respectively. In E coli -inoculated and MRSA-inoculated rifampicin-gelatin grafts, all of the eight animals had perigraft abscess, and blood culture test results probed septicemia in five animals with patent grafts at death. Inhibition zones against E coli or MRSA were not formed on the plates streaked with the same organism, whereas initial inhibition zones of E coli -inoculated and MRSA-inoculated rifampicin-gelatin grafts on S epidermidis -streaked plates were 8.0 +/- 0.2 mm and 18.5 +/- 0.5 mm, respectively. In the MRSA group, however, recolonization of high minimal inhibitory concentration strains developed within the inhibition zones as early as 24 hours. Histologically, neither organisms nor inflammatory cells were found in S epidermidis -inoculated rifampicin-gelatin grafts and tissue ingrowth was recognized at 2 to 4 weeks, whereas E coli -inoculated and MRSA-inoculated rifampicin-gelatin grafts had aggressive neutrophil infiltration into the graft interstices, revealing establishment of uncontrollable graft infection.
These results suggested that rifampicin-gelatin grafts are clearly valid for S epidermidis infection, whereas no efficacy was recognized against either MRSA or E coli graft infection because of early development of high minimal inhibitory concentration MRSA strains or poor susceptibility.
在动物模型中评估利福平 - 明胶移植物对强毒力微生物的抗菌活性及其持续时间。
通过将Gelseal(Vascutek Ltd,苏格兰)移植物浸渍于1mg/mL利福平溶液中来制备利福平 - 明胶移植物。将利福平 - 明胶移植物(6cm长;n = 24)和作为对照的普通Gelseal移植物(n = 4)植入接种了表皮葡萄球菌、大肠杆菌或耐甲氧西林金黄色葡萄球菌(MRSA)的犬腹主动脉中,并在1至4周后取出利福平 - 明胶移植物。从取出的利福平 - 明胶移植物上切下的圆盘置于接种了其中一种微生物的琼脂平板上,通过抑菌圈宽度评估移植物的抗菌活性。
在体外试验中,利福平 - 明胶移植物对表皮葡萄球菌、MRSA和大肠杆菌的初始抑菌圈(培养24小时后的抑菌圈)分别为40.0±0.3mm、36.0±0.2mm和11.8±0.1mm。在植入过程中,接种表皮葡萄球菌的利福平 - 明胶移植物未发现移植物感染,接种周围液体的平板上未发现菌落生长。在1周或2周时取出的接种表皮葡萄球菌的利福平 - 明胶移植物的初始抑菌圈分别为20.1±1.1mm和7.6±1.0mm。在接种大肠杆菌和MRSA的利福平 - 明胶移植物中,所有8只动物均有接种周围脓肿,5只存活时移植物通畅的动物血培养结果显示有败血症。在接种相同微生物的平板上未形成针对大肠杆菌或MRSA的抑菌圈,而接种大肠杆菌和MRSA的利福平 - 明胶移植物在接种表皮葡萄球菌的平板上的初始抑菌圈分别为8.0±0.2mm和18.5±0.5mm。然而,在MRSA组中,早在24小时内抑菌圈内就出现了高最低抑菌浓度菌株的重新定植。组织学上,接种表皮葡萄球菌的利福平 - 明胶移植物中未发现微生物和炎性细胞,在2至4周时可见组织向内生长,而接种大肠杆菌和MRSA的利福平 - 明胶移植物有大量中性粒细胞浸润到移植物间隙,表明发生了无法控制的移植物感染。
这些结果表明,利福平 - 明胶移植物对表皮葡萄球菌感染明显有效,而对MRSA或大肠杆菌移植物感染均无效果,原因是高最低抑菌浓度MRSA菌株的早期出现或敏感性较差。