Abstract: Background　Bacterial infection is the most important cause of diabetic lower extremity ulcer healing delay and amputation.The increasing resistance of bacteria to multiple antibiotics and inadequate lower extremity blood perfusion limit the efficacy of systemic antibiotic therapy.Photodynamic antimicrobial chemotherapy（PACT） is a promising approach for the treatment of chronic ulcer infections.Recently，available clinical evidence for methylene blue-mediated PACT （MB-PACT） for diabetic lower limb ulcer infection is limited.Objective　To investigate the efficacy and safety of MB-PACT for diabetic lower extremity ulcer infection using a pilot approach.Methods　The patients with diabetic lower extremity ulcer infection hospitalized in the Endocrinology Department of the First Affiliated Hospital of Chongqing Medical University from March 2019 to February 2020 were included and divided randomly into the experimental group（15 patients） and the control group（15 patients），using a computer generated pseudorandom permutation procedure.Besides standard treatment （hypoglycemic，antibacterial，lipid regulation，vascular circulation improvement，etc.），the experimental group was given MB-PACT，and the control group was given phototherapy for 7 days，respectively.The intensity of defined daily doses （DDDs） for antibacterial，pre- and post-treatment inflammation score and area of ulcer surface，routine blood test results and CRP level，bacterial load in the ulcer pre-treatment and immediately，and 4 and 7 days after treatment were compared between the two groups.Treatment-emergent adverse reactions were evaluated.Results　There was no statistically significant difference in DDDs for antibacterial between the two groups（P<0.05）.At 7 days post-treatment，in the experimental group，PEDIS grade decreased from grade 2 to grade 1 in 60% of patients（9/15），while that did not significantly decrease in the control group.However，ulcer size showed no significant improvement in each group（P>0.05）.And it was still similar across the two groups despite receiving treatment（P>0.05）.Serum CRP in the experiment group was similar to that of control group before treatment and 7 days after treatment，but decreased significantly after 7 days of treatment（P<0.05）.A decrease in the bacterial load in the ulcer was seen in the experimental group immediately，4 and 7 days after treatment and in the control group 4 and 7 days after treatment（P<0.05）.The experimental group was found with less bacterial load in the ulcer 4 and 7 days after treatment than the control group（P<0.05）.No adverse reactions，such as erythema，swelling，pain，pruritus，were observed during treatment in both groups.Conclusion　MB-PACT may improve the efficacy on ulcer infection by reducing the bacterial load and the inflammatory reaction in the ulcer surface with good safety for diabetic lower extremity ulcer infection patients，providing a basis for the development of new adjuvant treatment for diabetic lower extremity ulcer.

Key words: Diabetes complications, Diabetic lower extremity ulcer, Photodynamic antibacterial chemotherapy, Methylene blue, Bacterial load

摘要： 背景　细菌感染是导致糖尿病下肢溃疡迁延不愈甚至截肢的最主要原因。由于多药耐药菌增加且多数糖尿病下肢溃疡患者存在下肢灌注不足，全身用抗菌药物效果有限。光动力抗菌化学治疗（PACT）是一种有前景的治疗慢性创面感染的方法。目前，通过亚甲蓝（MB）介导PACT改善糖尿病下肢溃疡感染的临床研究证据较少。目的　初步探究MB介导PACT对糖尿病下肢溃疡感染的疗效及安全性。方法　选取2019年3月—2020年2月在重庆医科大学附属第一医院内分泌科住院的糖尿病下肢溃疡感染患者为研究对象。根据计算机产生的随机数字表将研究对象分为试验组和对照组，各15例。在实施标准治疗（降糖、抗菌、调脂、改善血液循环等治疗）的基础上，试验组予以MB介导PACT，对照组仅给予单纯光照，均治疗7 d。比较两组患者抗菌药物使用强度，治疗前及治疗7 d后溃疡面炎症情况和面积、血常规、C反应蛋白（CRP），治疗前、治疗后即刻、治疗4 d后、治疗7 d后溃疡创面细菌负荷；并评估不良反应发生情况。结果　两组患者抗菌药物使用强度〔累计用药频度（DDDs）〕比较，差异无统计学意义（P>0.05）。治疗7 d后试验组溃疡创面PEDIS分级由2级转为1级9例（9/15），而对照组溃疡创面PEDIS分级无变化。两组患者治疗前、治疗7 d后溃疡面积（组间、组内）比较，差异无统计学意义（P>0.05）。两组患者治疗前、治疗7 d后CRP比较，差异无统计学意义（P>0.05）。试验组患者治疗7 d后CRP低于治疗前（P<0.05）。试验组患者治疗4、7 d后溃疡创面细菌负荷低于对照组（P<0.05）；试验组患者治疗后即刻和治疗4、7 d后溃疡创面细菌负荷低于治疗前（P<0.05）；对照组患者治疗4、7 d后溃疡创面细菌负荷低于治疗前（P<0.05）。两组患者治疗过程中均未出现红斑、肿胀、疼痛、瘙痒等不良反应。结论　MB介导PACT可通过降低溃疡创面细菌负荷、减轻炎性反应而改善糖尿病下肢溃疡感染，且有良好的安全性，可为糖尿病下肢溃疡感染新的辅助治疗提供参考。

关键词: 糖尿病并发症, 糖尿病下肢溃疡, 光动力抗菌治疗, 亚甲蓝, 细菌负荷