Bacteriophage treatment of intransigent diabetic toe ulcers: a case series
Bacteriophage treatment of intransigent diabetic toe ulcers: a case series
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DOI：
10.12968/jowc.2016.25.sup7.s27
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发表时间：
2016-07-01
影响因子：
1.9
通讯作者：
Kuhl, S.
中科院分区：
文献类型：
--
作者：
Fish, R.;Kutter, E.;Kuhl, S.
目的：糖尿病足溃疡（DFU）感染是一个日益严重的公共卫生问题，其患病率不断上升，对抗生素的反应较差，细菌对传统抗菌素的耐药性导致发病率和死亡率增加。噬菌体（噬菌体）是针对特定细菌的病毒，是解决细菌感染的一种选择，特别是在抗生素失效的情况下。特别有价值的是一类强毒的葡萄球菌噬菌体，它可以攻击几乎所有的金黄色葡萄球菌，包括大多数耐甲氧西林金黄色葡萄球菌（MRSA）菌株。在这里，我们报告了一个连续的病例系列，评估了在推荐的抗生素治疗失败后，局部应用金黄色葡萄球菌特异性噬菌体治疗感染和血管不良的暴露骨脚趾溃疡的有效性。方法：这是一个同情用例系列，9例糖尿病患者和含有培养证实的金黄色葡萄球菌感染的骨和软组织的灌注不良的脚趾溃疡，他们对推荐的抗生素治疗反应不佳。本文介绍了六个具有代表性的案例。在每个病例中，唯一被普遍接受的其他选择是脚趾截肢。3例被感染指骨的暴露部分被切除，2例被保留。一例血管支架植入术后出现微凝块引起的坏疽。在这种情况下，噬菌体被用来预防感染。所使用的噬菌体是市售的葡萄球菌噬菌体Sb-1的全测序制剂。噬菌体溶液应用于溃疡局部每周一次，遵循标准的良好伤口护理。根据溃疡的体积和面积，噬菌体溶液的用量从0.1到0.5 cc不等。结果：所有感染对噬菌体应用有反应，溃疡在感染骨清创的平均7周内愈合。一例溃疡，其中血管性极差，没有去骨以保持拇功能，需要18周的治疗。在脚趾有微凝块坏疽的情况下，脚趾在七周内被修复并愈合，没有并发症。结论：局部应用单噬菌体制剂可以成功地治疗感染的脚趾溃疡伴骨累及，尽管非常差的血管和抗生素治疗失败。这个小系列的成功为糖尿病足感染的葡萄球菌噬菌体对照临床试验提供了基础。
Objective: Diabetic foot ulcer (DFU) infections are a growing public health problem, with increasing prevalence, poor response to antibiotics and bacterial resistance to traditional antimicrobials leading to increased morbidity and mortality. Bacteriophages (phages), the viruses that target specific bacteria, are one option for addressing bacterial infections, especially where antibiotics fail. Of particular value is a class of virulent staphylococcal phages that hit almost all Staphylococcus aureus, including most methicillin-resistant Staphylococcus aureus (MRSA) strains. Here we report a continuous case series assessing the effectiveness of treating infected and poorly vascularised toe ulcers with exposed bone, after failure of recommended antibiotic therapy, using topically applied Staphylococcus aureus-specific phage.Method: This was a compassionate-use case series of nine patients with diabetes and poorly perfused toe ulcers containing culture-proven Staphylococcus aureus infected bone and soft tissue, who had responded poorly to recommended antibiotic therapy. Six representative cases are presented here. The only generally accepted other option in each case was toe amputation. Exposed portions of the infected phalanges were removed in three cases and left in place in two cases. One case presented as a micro-clot induced gangrene following vascular stenting. In this case, phage were used to prevent infection. The phage used was a commercially available fully sequenced preparation of staphylococcal phage Sb-1. Phage solution was applied topically to the ulcerations once weekly, following standard good wound care. The amount of phage solution applied varied from 0.1 to 0.5 cc depending on volume and area of the ulceration.Results: All infections responded to the phage applications and the ulcers healed in an average of seven weeks with infected bone debridement. One ulcer, where vascularity was extremely poor and bone was not removed to preserve hallux function, required 18 weeks of treatment. In the case of the toe with the micro-clot gangrene, the toe was salvaged and healed in seven weeks without complications.Conclusion: Topical application of a staph mono-phage preparation can be used successfully to treat infected toe ulcerations with bone involvement, despite very poor vascularity and failure of antibiotic treatment. The success within this small series provides the groundwork for controlled clinical trials of staph phage for diabetic foot infections.