Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center, Rochester, New York.
Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York.
J Orthop Res. 2019 Jul;37(7):1596-1603. doi: 10.1002/jor.24279. Epub 2019 Mar 28.
Diabetic foot ulcers (DFU) contribute to 80% of lower extremity amputations. Although physicians currently rely on clinical signs along with non-specific biomarkers of infection, such as erythrocyte sedimentation rate and C-reactive protein, to diagnose and monitor DFU, there is no specific and sensitive measure available to monitor or prognosticate the success of foot salvage therapy (FST). To address this we performed a prospective, observational microbiome analysis to test the hypotheses that: (i) the initial microbiomes of healed versus non-healed DFU are distinct; (ii) the microbial load, diversity and presence of pathogenic organism of the DFU change in response to antibiotics treatment; and (iii) the changes in the DFU microbiome during treatment are prognostic of clinical outcome. To test this, microbiome analyses were performed on 23 DFU patients undergoing FST, in which wound samples were collected at zero, four, and eight weeks following wound debridement and antibiotics treatment. Bacterial abundance was determined using quantitative polymerase chain reaction (qPCR). Eleven patients healed their DFU, while FDT failed to heal DFU in the other 12 patients. Microbiome results demonstrated that healing DFUs had a larger abundance Actinomycetales and Staphylococcaceae (p < 0.05), while DFUs that did not heal had a higher abundance of Bacteroidales and Streptococcaceae (p < 0.05). FST marked increases Actinomycetales in DFU, and this increase is significantly greater in patients that healed (p < 0.05). Future studies to confirm the differential microbiomes, and that increasing Actinomycetales is prognostic of successful FST are warranted. Statement of Clinical Significance: Tracking changes in the prevalence of pathogens in diabetic foot ulcers may be a clinical tool for monitoring treatment response to foot salvage therapy and prognosticating the need for further surgical intervention. The initial wound sample microbiome may provide important prognostic information on the eventual clinical outcome of foot salvage therapy. It may serve as an important clinical tool for patient counseling and making surgical decision of pursuing foot salvage versus amputation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1596-1603, 2019.
糖尿病足溃疡（DFU）占下肢截肢的 80%。尽管医生目前依赖临床症状以及感染的非特异性生物标志物，如红细胞沉降率和 C 反应蛋白，来诊断和监测 DFU，但目前尚无可用的特定和敏感措施来监测或预测足部保存治疗（FST）的成功。为了解决这个问题，我们进行了一项前瞻性、观察性的微生物组分析，以检验以下假设：（i）愈合的 DFU 与未愈合的 DFU 的初始微生物组是不同的；（ii）DFU 的微生物负荷、多样性和致病生物体的存在因抗生素治疗而改变；（iii）治疗过程中 DFU 微生物组的变化是临床结果的预测因素。为了验证这一点，对 23 例接受 FST 的 DFU 患者进行了微生物组分析，其中在清创和抗生素治疗后 0、4 和 8 周采集伤口样本。使用定量聚合酶链反应（qPCR）测定细菌丰度。11 例患者的 DFU 愈合，而其余 12 例患者的 FDT 未能治愈 DFU。微生物组结果表明，愈合的 DFU 中有大量放线菌目和葡萄球菌科（p<0.05），而未愈合的 DFU 中则有大量拟杆菌目和链球菌科（p<0.05）。FST 使 DFU 中的放线菌目显著增加，而在愈合的患者中增加更为显著（p<0.05）。需要进一步的研究来确认差异微生物组，以及放线菌目的增加是 FST 成功的预测指标。临床意义声明：跟踪糖尿病足溃疡中病原体流行率的变化可能是监测足部保存治疗反应并预测是否需要进一步手术干预的临床工具。初始伤口样本微生物组可能为足部保存治疗的最终临床结果提供重要的预后信息。它可以作为患者咨询和决定进行足部保存治疗还是截肢的重要临床工具。2019 年骨科研究协会。由 Wiley Periodicals，Inc. 出版。J Orthop Res 37:1596-1603，2019.
