中文摘要：随着多药耐药（MDR）细菌的出现，伤口感染问题成为了一个相当大的医疗负担。本研究以IME-AB2噬菌体和MDR-AB2为模型噬菌体和细菌，探讨噬菌体热敏凝胶在治疗MDR鲍曼不动杆菌致伤口感染中的应用。首次证明IME-AB2噬菌体在-18 wt%泊洛沙姆407（P407）水凝胶溶液中具有良好的储存稳定性，在4℃下24个月内滴度损失可忽略。在37℃下，噬菌体凝胶和噬菌体悬液对鲍曼不动杆菌的体外杀灭率>5log(10) CFU/ml。比较了噬菌体凝胶和噬菌体悬浮液的生物膜清除能力（分别为59%和45%）。研究表明，将噬菌体掺入水凝胶，不仅不会影响噬菌体的杀灭效果，还可以作为噬菌体库，在感染部位保持较高的滴度，延长高效治疗时间。此外，水凝胶制剂在猪皮离体伤口感染模型中显著抑制了微生物的存活（处理4小时后，细菌数量减少了90%）。可见，p407噬菌体热敏水凝胶是一种简单而有前途的噬菌体制剂，可用于处理伤口感染。
外文摘要：With the emergence of multidrug resistance (MDR) bacteria, wound infection continues to be a challenging problem and represents a considerable healthcare burden. This study aims to evaluate the applicability of a phage loaded thermosensitive hydrogel in managing wound infections caused by MDR Acinetobacter baumannii, using IME-AB2 phage and MDR-AB2 as the model phage and bacteria, respectively. Excellent storage stability of the IME-AB2 phage in a -18 wt% Poloxamer 407 (P407) hydrogel solution was first demonstrated with negligible titer loss (-0.5 log) in 24 months at 4 degrees C. The incorporated phage was released in a sustained manner with a cumulative release of 60% in the first 24 h. The in vitro bacterial killing efficiency of phage gel and phage suspension at 37 degrees C demonstrated >5 log(10) CFU/ml reduction against A. baumannii. A comparable biofilm elimination capacity was also noted between the phage gel and phage suspension (59% and 45% respectively). These results suggested that the incorporation of phage into the hydrogel not only had insignificant impacts on the bacterial killing efficiency of phage, but also act as a phage depot to maintain higher phage titer at the infectious site for a prolong period for more effective treatment. We also found that the hydrogel formulation significantly suppressed microbial survival in an ex vivo wound infection model using pig skin (90% reduction in bacterial counts was achieved after 4 h treatment). In summary, our results demonstrated that the P407-based phage-loaded thermosensitive hydrogel is a simple and promising phage formulation for the management of wound infections.
外文关键词：Multidrug resistance (MDR)；Wound infections；Phage therapy； Thermosensitive hydrogel；Poloxamer 407
作者：Yan, W；Banerjee, P；Liu, YN；Mi, ZQ；Bai, CQ；Hu, HY；To, KKW；Duong, HTT； Leung, SSY
作者单位：Chinese Univ Hong Kong；Capital Med Univ；Beijing Inst Microbiol & Epidemiol； Chinese Peoples Liberat Army Gen Hosp；Sun Yat Sen Univ；Univ Sydney
期刊名称：INTERNATIONAL JOURNAL OF PHARMACEUTICS
期刊影响因子：4.845
出版年份：2021
出版刊次：602
点击下载：防伤口感染的鲍曼不动杆菌噬菌体热敏水凝胶创面敷料的研制