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在兔开放性骨折模型中,损伤后早期局部应用载有庆大霉素的水凝胶优于围手术期全身预防性用药。

Local Application of a Gentamicin-Loaded Hydrogel Early After Injury Is Superior to Perioperative Systemic Prophylaxis in a Rabbit Open Fracture Model.

作者信息

Vallejo Diaz Alejandro, Deimling Christian, Morgenstern Mario, D'Este Matteo, Puetzler Jan, Zeiter Stephan, Arens Daniel, Metsemakers Willem-Jan, Richards R Geoff, Eglin David, Moriarty T Fintan

机构信息

AO Research Institute Davos, Davos, CH.

Orthopaedic Service, IPS Universitaria, Servicios de Salud Universidad de Antioquia, Medellin, Columbia.

出版信息

J Orthop Trauma. 2020 May;34(5):231-237. doi: 10.1097/BOT.0000000000001707.

DOI:10.1097/BOT.0000000000001707
PMID:32304564
Abstract

OBJECTIVES

Open fractures are at significant risk of developing a fracture-related infection, despite the routine administration of perioperative antibiotic prophylaxis. Early application of antibiotic prophylaxis is known to reduce infection rates; however, most international guidelines focus on postoperative duration rather than prehospital administration. We compared conventional perioperative prophylaxis against early prehospital prophylaxis either as a systemic single shot of cefuroxime or a locally applied gentamicin-loaded hydrogel in a laboratory animal model.

METHODS

Thirty New Zealand white rabbits underwent a first surgical procedure to create an open wound, bone damage and contamination with Staphylococcus aureus. After a 4-hour observation period mimicking the time-to-treatment, the animals underwent a second procedure to irrigate the wound and apply a fracture fixation device. The 5 groups (n = 6 per group) received (1) no treatment; (2) conventional 24-hour cefuroxime; (3) an early single shot of cefuroxime 15 minutes after trauma; (4) a combined early and standard systemic prophylaxis; and (5) early application of a gentamicin-loaded hydrogel that was removed during irrigation.

RESULTS

Untreated animals displayed high numbers of bacteria in irrigation fluid and were all highly culture positive at euthanasia. Three of 6 animals were culture positive at euthanasia after conventional prophylaxis. Early systemic prophylaxis reduced bacterial burden in irrigation fluid by up to 100-fold, but 5/6 animals were culture positive at euthanasia. The combined prophylaxis displayed greater efficacy with only 1/6 rabbits culture positive at euthanasia. Local application of the gentamicin-loaded hydrogel reduced bacteria recovered by irrigation to just above our detection limit, and at euthanasia, all animals were culture negative at euthanasia.

CONCLUSIONS

Early systemic antibiotic administration can significantly reduce bacterial burden in the operative field and reduce culture positivity at euthanasia when continued for 24 hours after injury. The early application of a gentamicin-loaded hydrogel that was removed during irrigation displayed superior efficacy to early systemic therapy alone and postoperative conventional gold standard 24-hour systemic therapy alone. These experimental results highlight the importance of early antibiotic administration in fracture care.

摘要

目的

尽管围手术期常规使用抗生素预防,但开放性骨折仍有发生骨折相关感染的重大风险。已知早期应用抗生素预防可降低感染率;然而,大多数国际指南关注的是术后使用时长,而非院前给药。我们在实验动物模型中比较了传统围手术期预防与早期院前预防,早期院前预防采用头孢呋辛单次全身注射或局部应用含庆大霉素的水凝胶。

方法

30只新西兰白兔接受首次外科手术,造成开放性伤口、骨损伤并感染金黄色葡萄球菌。在模拟治疗时间的4小时观察期后,动物接受第二次手术,冲洗伤口并应用骨折固定装置。5组(每组n = 6)分别接受:(1) 不治疗;(2) 传统的24小时头孢呋辛治疗;(3) 创伤后15分钟早期单次注射头孢呋辛;(4) 早期和标准全身预防联合应用;(5) 早期应用含庆大霉素的水凝胶,在冲洗时移除。

结果

未治疗的动物冲洗液中细菌数量多,安乐死时全部培养呈强阳性。传统预防后,6只动物中有3只在安乐死时培养呈阳性。早期全身预防使冲洗液中的细菌负荷降低多达100倍,但安乐死时5/6的动物培养呈阳性。联合预防效果更佳,安乐死时只有1/6的兔子培养呈阳性。局部应用含庆大霉素的水凝胶使冲洗回收的细菌减少到略高于我们的检测限,安乐死时所有动物培养均为阴性。

结论

早期全身应用抗生素可显著降低手术部位的细菌负荷,并在受伤后持续24小时使用时降低安乐死时的培养阳性率。冲洗时移除的含庆大霉素水凝胶的早期应用显示出优于单独早期全身治疗和术后传统金标准24小时全身治疗的疗效。这些实验结果凸显了早期应用抗生素在骨折治疗中的重要性。

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