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新型叶绿素衍生物生泰倍芬(STBF)介导的光动力疗法联合碘伏治疗耐甲氧西林金黄色葡萄球菌慢性下肢浅表性创面感染:一项回顾性临床研究。

A novel chlorin derivative Shengtaibufen (STBF) mediated photodynamic therapy combined with iodophor for the treatment of chronic superficial leg wounds infected with methicillin-resistant Staphylococcus aureus: A retrospective clinical study.

机构信息

Department of Dermatology, Huadong Hospital, Fudan University, Shanghai 200040, PR China.

Department of Dermatology, Shanghai Fengxian District Hospital, Shanghai 201499, PR China.

出版信息

Photodiagnosis Photodyn Ther. 2024 Aug;48:104300. doi: 10.1016/j.pdpdt.2024.104300. Epub 2024 Aug 2.

Abstract

OBJECTIVE

Chronic wounds are costly and difficult to treat, resulting in morbidity and even mortality in some cases due to a high methicillin-resistant Staphylococcus aureus (MRSA) burden contributing to chronicity. We aimed to observe the antimicrobial activity and healing-promoting effect of a novel photosensitizer Shengtaibufen (STBF)-mediated antibacterial photodynamic therapy (PDT) on MRSA-infected chronic leg ulcers.

PATIENTS AND METHODS

This was a retrospective, comparative, single-center clinical study. A total of 32 patients with chronic lower limb wounds infected with MRSA from January 2022 to December 2023 were finally included in this study by searching the electronic medical records of the dermatology department of Huadong Hospital, including a group of red light combined with iodophor (control+iodophor, n=16, receiving red light once a week for 8 weeks and routine dressing change with iodophor once a day) and a group of STBF-mediated PDT (STBF-PDT) combined with iodophor (STBF-PDT+iodophor, n=16, receiving STBF-PDT and routine dressing change with iodophor once a day). STBF-PDT was performed once a week (1 mg/ml STBF, 1 h incubation, 630 nm red light, 80 J/cm) for 8 weeks. The primary endpoints included wound clinical signs, wound size, wound-related pain, re-epithelialization score, MRSA load and wound-related quality of life (wound-QoL). Any adverse events were also recorded.

RESULTS

We found that STBF-PDT+iodophor could effectively alleviate clinical infection symptoms, accelerate wound closure, reduce average biological burden and improve wound-QoL without severe adverse events in comparison to the control+iodophor group. The STBF-PDT+iodophor group obtained a mean percentage reduction of 65.22% in wound size (from 18.96±11.18 cm to 6.59±7.94 cm) and excellent re-epithelialization scores, as compared with a decrease of 30.17% (from 19.23±9.80 cm to 13.43±9.32 cm) for the control+iodophor group. Significant differences in wound area were observed at week 6 (p=0.028*) and week 8 (p=0.002**). The bacterial load decreased by 99.86% (from 6.45 × 10±2.69 × 10 to 8.94 × 10±1.92 × 10 CFU/cm, p<0.0001) in the STBF-PDT+iodophor group and 1.82% (from 6.61 × 10±2.13 × 10 to 6.49 × 10±2.01 × 10 CFU/cm, p=0.029) in the control+iodophor group. The wound-QoL in STBF-PDT+iodophor group had a 51.62% decrease in overall score (from 29.65±9.33 at the initial to 14.34±5.17 at week 8, p<0.0001) compared to those receiving red light and routine wound care (from 30.73±17.16 to 29.32±15.89 at week 8, p=0.003). Moreover, patients undergoing STBF-PDT+iodophor exhibited great improvements in all domains of wound-QoL (physical, psychological and everyday-life), whereas the control+iodophor group ameliorated in only one field (everyday-life).

CONCLUSION

Our data confirmed that a novel photosensitizer, STBF-mediated PDT, when combined with iodophor, served as a potential modality for MRSA infection and a possible therapy for other drug-resistant microorganisms, and as a promising alternative for chronic cutaneous infectious diseases.

摘要

目的

慢性伤口治疗费用高且难度大,某些情况下由于耐甲氧西林金黄色葡萄球菌(MRSA)负担过高导致慢性化,进而导致发病率甚至死亡率。我们旨在观察新型光敏剂替硝唑布芬(STBF)介导的光动力疗法(PDT)对 MRSA 感染慢性下肢溃疡的抗菌活性和促进愈合作用。

患者和方法

这是一项回顾性、对照、单中心临床研究。通过检索华东医院皮肤科电子病历,最终纳入了 2022 年 1 月至 2023 年 12 月期间 32 例 MRSA 感染慢性下肢伤口的患者,分为红光联合碘伏组(对照组+碘伏,n=16,每周接受红光治疗一次,共 8 周,每天常规更换碘伏敷料)和 STBF-PDT 联合碘伏组(STBF-PDT+碘伏,n=16,每天常规更换碘伏敷料,同时每周接受 STBF-PDT 治疗 1 次)。STBF-PDT 治疗方案为 1mg/ml STBF,孵育 1h,630nm 红光,80J/cm2。主要终点包括伤口临床体征、伤口大小、伤口相关疼痛、再上皮化评分、MRSA 负荷和伤口相关生活质量(伤口-QoL)。记录任何不良事件。

结果

与对照组+碘伏组相比,STBF-PDT+碘伏组能有效缓解临床感染症状,加速伤口愈合,减少平均生物负荷,改善伤口-QoL,且无严重不良事件。与对照组+碘伏组的 30.17%(从 19.23±9.80cm 减少至 13.43±9.32cm)相比,STBF-PDT+碘伏组的伤口面积减少了 65.22%(从 18.96±11.18cm 减少至 6.59±7.94cm),且再上皮化评分优异。在第 6 周(p=0.028*)和第 8 周(p=0.002**)观察到伤口面积的显著差异。STBF-PDT+碘伏组的细菌负荷下降了 99.86%(从 6.45×10±2.69×10 减少至 8.94×10±1.92×10 CFU/cm,p<0.0001),而对照组+碘伏组仅下降了 1.82%(从 6.61×10±2.13×10 减少至 6.49×10±2.01×10 CFU/cm,p=0.029)。与对照组+碘伏组相比,STBF-PDT+碘伏组的伤口-QoL 总评分下降了 51.62%(从初始的 29.65±9.33 降至第 8 周的 14.34±5.17,p<0.0001),而对照组+碘伏组的评分从 30.73±17.16 降至第 8 周的 29.32±15.89(p=0.003)。此外,接受 STBF-PDT+碘伏治疗的患者在伤口-QoL 的所有领域(身体、心理和日常生活)均有明显改善,而对照组+碘伏组仅在日常生活领域有所改善。

结论

我们的数据证实,新型光敏剂替硝唑布芬(STBF)介导的 PDT 联合碘附,作为一种治疗 MRSA 感染的潜在方法和其他耐药微生物的可能治疗方法,为慢性皮肤感染性疾病提供了一种有前途的替代方法。

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