Pilot Clinical Study Of Methylene Blue Mediated Photodynamic Antibacterial Chemotherapy To Improve Diabetic Lower Extremity Ulcer Infection

Background Diabetic lower extremity ulcer infection has a high incidence,if not properly treated,it can worsen the patient’s condition,increase amputation and mortality rates.Currently,guidelines are recommend with general antimicrobial therapy combined with surgical treatment for diabetic lower extremity ulcer infection.However,due to insufficient lower extremity perfusion in most diabetic lower extremity ulcer patients,antimicrobial drugs are difficult to reach the therapeutic target,and systemic antimicrobial drugs have limited effect.Therefore,it is urgent to develop a new adjuvant antimicrobial therapy to improve the treatment outcome of diabetic lower extremity ulcer infection.Photodynamic antimicrobial chemotherapy(PACT)is a kind of chemotherapy for local microbe inactivation induced by light irradiation,which does not depend on local blood supply and non-specific antibacterial,and is not easy to produce drug-resistant bacteria and damage the surrounding tissues.It is considered as a promising method for the treatment of chronic infection.However,it have been rarely reported with PACT for treatment of diabetic lower extremity ulcer infection by 6 randomized controlled clinical studies.Objective To preliminarily investigate the efficacy and safety of methylene blue mediated photodynamic antibacterial chemotherapy(MB-PACT)for diabetic lower extremity ulcer infection,explore a new adjuvant therapy for diabetic lower extremity ulcer infection.Methods The diabetic lower extremity ulcer infection patients hospitalized in the Endocrinology Department of the First Affiliated Hospital of Chongqing Medical University from March2019 to February 2020 were recruited.According to intervention with MB-PACT,the patients were divided into the experimental group(15patients)and the control group(15 patients).In addition to standard treatment(hypoglycemic,antibacterial,lipid regulation,vascular circulation improvement,etc.)for the patients recruited,the experimental group was given with MB-PACT,and the control group was given with irradiation alone.The inflammation score,ulcer area,and skin irritation adverse reaction in the infected lower extremity ulcer surface of two groups were observed.Bacterial load in the ulcer surface was detected by bacterial culture,blood routine and C-reactive protein levels were routinely tested,the efficacy and adverse reactions of MB-PACT were evaluated on the basis of measure outcomes.Results In the experimental group,ulcer inflammation score decreased from grade 2 to grade 1 with60% of patients(9/15),while the inflammation score in the control group did not significantly decrease.However,the ulcer area in both groups did not significantly decrease on 7 days after treatment(P > 0.05).Compared with before treatment,the total reduction of bacterial load after treatment immediate in the experimental group(1.86 ± 0.75log10CFU/ml)was significantly higher than that in the control group(0.27± 0.28 log10CFU/ml)(P < 0.01);On day 4 with treatment,the bacterial load in the experimental group(3.1 ± 1.0 log10CFU/ml)was lower than that of the control group(5.1 ± 1.4 log10CFU/ml),and the difference was statistically significant(P < 0.01);On day 7 with treatment,the bacterial load in the experimental group(1.8 ± 0.3 log10CFU/ml)was lower than that of the control group(3.7 ± 1.6 log10CFU/ml),and the difference was statistically significant(P < 0.01).On the 7th day with treatment,the C-reactive protein level in serum in the experimental group(16.3 ± 29.8mg/L)was significantly lower than that of before treatment(26.1 ± 31.1mg/L)(P = 0.011).There were not observed with adverse reactions such as erythema,swelling,pain,blister during irradiation treatment.Conclusion Methylene blue mediated photodynamic antibacterial chemotherapy can improve efficacy of the infection in diabetic lower extremity ulcer by reducing the bacterial load in the ulcer surface and reducing the inflammatory reaction,and has good safety,which can provide clinical application basis for the new adjuvant treatment with diabetic lower extremity ulcer.