Islam Anoy Md Monzurul, Kim Won-Jun, Gelston Suzanne, Fleming Derek, Patel Robin, Beyenal Haluk
The Gene and Linda Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA 99164, USA.
Division of Clinical Microbiology, Mayo Clinic, Rochester, Minnesota 55905, USA.
bioRxiv. 2024 Mar 27:2024.03.22.586337. doi: 10.1101/2024.03.22.586337.
Chronic wound infections can be difficult to treat and may lead to impaired healing and worsened patient outcomes. Novel treatment strategies are needed. This study evaluated effects of intermittently produced HO and HOCl, generated via an electrochemical bandage (e-bandage), against methicillin-resistant biofilms in an agar membrane biofilm model. By changing the working electrode potential, the e-bandage generated either HOCl (1.5 V) or HO (-0.6 V). The degree of biocidal activity of intermittent treatment with HOCl and HO correlated with HOCl treatment time; HOCl treatment durations of 0, 1.5, 3, 4.5, and 6 hours (with the rest of the 6 hour total treatment time devoted to HO generation) resulted in mean biofilm reductions of 1.36±0.2, 2.22±0.16, 3.46±0.38, 4.63±0.74 and 7.66±0.5 log CFU/cm, respectively vs. non-polarized controls, respectively. However, application of HO immediately after HOCl treatment was detrimental to biofilm removal. For example, 3-hours HOCl treatment followed by 3-hours HO resulted in a 1.90±0.84 log CFU/cm lower mean biofilm reduction than 3-hours HOCl treatment followed by 3-hours non-polarization. HOCl generated over 3-hours exhibited biocidal activity for at least 7.5-hours after e-bandage operation ceased; 3-hours of HOCl generation followed by 7.5-hours of non-polarization resulted in a biofilm cell reduction of 7.92±0.12 log CFU/cm vs. non polarized controls. Finally, intermittent treatment with HOCl (i.e., interspersed with periods of e-bandage non-polarization) for various intervals showed similar effects (approximately 6 log CFU/cm reduction vs. non-polarized control) to continuous treatment with HOCl for 3-hours, followed by 3-hours of non-polarization. These findings suggest that timing and sequencing of HOCl and HO treatments are crucial for maximizing biofilm control.
慢性伤口感染可能难以治疗,并可能导致愈合受损和患者预后恶化。需要新的治疗策略。本研究在琼脂膜生物膜模型中评估了通过电化学绷带(电子绷带)间歇性产生的次氯酸(HOCl)和过氧化氢(HO)对耐甲氧西林生物膜的作用。通过改变工作电极电位,电子绷带可产生HOCl(1.5伏)或HO(-0.6伏)。HOCl和HO间歇治疗的杀菌活性程度与HOCl治疗时间相关;HOCl治疗持续时间为0、1.5、3、4.5和6小时(6小时总治疗时间的其余部分用于产生HO),与非极化对照相比,生物膜平均减少量分别为1.36±0.2、2.22±0.16、3.46±0.38、4.63±0.74和7.66±0.5 log CFU/cm。然而,在HOCl治疗后立即应用HO不利于生物膜的清除。例如,3小时HOCl治疗后接着3小时HO,其生物膜平均减少量比3小时HOCl治疗后接着3小时非极化低1.90±0.84 log CFU/cm。在电子绷带操作停止后,3小时产生的HOCl表现出至少7.5小时的杀菌活性;3小时产生HOCl后接着7.5小时非极化,与非极化对照相比,生物膜细胞减少量为7.92±0.12 log CFU/cm。最后,HOCl间歇治疗(即穿插电子绷带非极化期)不同时间间隔显示出与连续3小时HOCl治疗后接着3小时非极化相似的效果(与非极化对照相比生物膜减少约6 log CFU/cm)。这些发现表明,HOCl和HO治疗的时间安排和顺序对于最大化生物膜控制至关重要。