Limitations in the use of rifampicin-gelatin grafts against virulent organisms

Limitations in the use of rifampicin-gelatin grafts against virulent organisms
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DOI:
10.1067/mva.2002.121850
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发表时间:
2002-04-01
影响因子:
4.3
通讯作者:
Inaba, M
Inaba, M
中科院分区:
医学2区
文献类型:
--
作者:
Koshiko, S;Sasajima, T;Inaba, M

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目的:利福平-明胶移植物对有毒微生物的抗菌活性的效力和持续时间进行了评价,在animal model.Materials和方法:利福平-明胶移植物制备与Gelseal(Vascutek有限公司,苏格兰)移植物在1毫克/毫升利福平溶液浸渍。将利福平-明胶移植物(6 cm长; n = 24)和普通Gelseal移植物作为对照(n = 4)植入犬腹主动脉中,接种表皮葡萄球菌、大肠杆菌或耐甲氧西林金黄色葡萄球菌(MRSA),1 - 4周后取出利福平-明胶移植物。将从回收的利福平-明胶移植物上切下的细菌置于用其中一种微生物划线的琼脂平板上,并通过抑制区的宽度来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(孵育后24小时的抑菌圈)分别为40.0 +/- 0.3 mm、36.0 +/- 0.2 mm和11.8 +/- 0.1 mm。在植入过程中,表皮葡萄球菌接种的利福平-明胶移植物未发现移植物感染,在用移植物周围液体划线的平板上未发现菌落生长。在第1周或第2周取出的表皮葡萄球菌接种的利福平-明胶移植物的初始抑制区分别为20.1 ± 1.1 mm和7.6 ± 1.0 mm。在大肠杆菌接种和MRSA接种的利福平-明胶移植物中,所有8只动物都有移植物周围脓肿,血液培养试验结果在5只死亡时移植物未闭的动物中探测了败血症。在用相同微生物划线的平板上未形成针对大肠杆菌或MRSA的抑制区,而在Sepidermidis划线平板上接种大肠杆菌和接种MRSA的利福平-明胶移植物的初始抑制区分别为8.0 +/- 0.2 mm和18.5 +/- 0.5 mm。然而,在MRSA组中,早在24小时,高最小耐药浓度菌株在抑菌区内就发生了耐药。组织学上,在表皮葡萄球菌接种的利福平-明胶移植物中既没有发现生物体也没有发现炎性细胞,并且在2至4周时识别出组织向内生长,而大肠杆菌接种和MRSA接种的利福平-明胶移植物中有侵袭性中性粒细胞浸润到移植物间隙中,揭示了不可控制的移植物感染的建立。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,然而,由于早期出现了高最小耐药浓度的MRSA菌株,因此对MRSA或大肠杆菌移植物感染没有有效性,易感性差。
Objective: Efficacy and duration of antibacterial activity of rifampicin-gelatin grafts against virulent organisms were evaluated in an animal model.Materials and methods: 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 I 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.Results. 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 I 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 sa-me organism, whereas initial inhibition zones of E coli-inoculated and MRSA-inoculated rifampicin-gelatin grafts on Sepidermidis-streaked plates were 8.0 +/- 0.2 mm and 18.5 +/- 0.5 mm, respectively. In the MRSA group, however, recolonization of high minimal inhibitary 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.Conclusion, 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 inhibitary concentration MRSA strains or poor susceptibility.