Dong Ying, Li Junshuai, Li Pan, Yu Jialin
Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China.
Department of Neonatology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
J Ultrasound Med. 2018 Jun;37(6):1379-1387. doi: 10.1002/jum.14475. Epub 2017 Nov 21.
Staphylococcus epidermidis is the predominant pathogen of device-associated infections. By forming biofilms on the device surface, S epidermidis has substantial resistance to antibiotics and is difficult to eradicate. This study aimed to explore the synergistic effect of ultrasound (US)-mediated microbubbles combined with vancomycin on S epidermidis biofilms in a rabbit model.
Two polytetrafluoroethene catheters with preformed S epidermidis biofilms were implanted subcutaneously in a rabbit, one on either side of the spine. Animals were randomized into different treatment groups, with each rabbit acting as its own control and treatment. Ultrasound was applied from 24 to 72 hours after surgery 2 times a day. The parameters were 300 kHz and 0.5 W/cm in a 50% duty cycle, with or without microbubbles injected subcutaneously into the implantation site. After treatments, animals were euthanized, and implants were removed for a scanning electron microscopic examination and bacterial counting. The hearts, kidneys, livers, and subcutaneous tissues were sent for histopathologic examinations.
Ultrasound + microbubbles increased the bactericidal action of vancomycin by decreasing biofilm viability from a mean ± SD of 6.44 ± 0.03 log colony-forming units per catheter in the control group to 3.49 ± 0.02 log colony-forming units per catheter in US + microbubble + vancomycin group (P < .001). The antibacterial effect of US + microbubbles + vancomycin was more pronounced than that of US + vancomycin (P < .001). Under scanning electron microscopy, biofilms exposed to US + microbubbles + vancomycin showed a greater reduction in thickness and bacterial density than other treatments. Histopathologic examinations showed no abnormalities in organs and skins.
Ultrasound microbubbles enhanced the antibacterial effect of vancomycin against S epidermidis biofilms in vivo without exerting obvious harms to the animals.
表皮葡萄球菌是与器械相关感染的主要病原体。通过在器械表面形成生物膜，表皮葡萄球菌对抗生素具有很强的耐药性，难以根除。本研究旨在探讨超声介导的微泡联合万古霉素对兔模型中表皮葡萄球菌生物膜的协同作用。
将两根预先形成表皮葡萄球菌生物膜的聚四氟乙烯导管皮下植入兔体内，分别位于脊柱两侧。将动物随机分为不同治疗组，每只兔自身作为对照和治疗对象。术后24至72小时每天进行2次超声治疗。参数为300kHz、0.5W/cm²、占空比50%，在植入部位皮下注射或不注射微泡。治疗后，对动物实施安乐死，取出植入物进行扫描电子显微镜检查和细菌计数。将心脏、肾脏、肝脏和皮下组织送去进行组织病理学检查。
超声 + 微泡增强了万古霉素的杀菌作用，使生物膜活力从对照组每根导管平均±标准差6.44±0.03 log菌落形成单位降至超声 + 微泡 + 万古霉素组的每根导管3.49±0.02 log菌落形成单位（P <.001）。超声 + 微泡 + 万古霉素的抗菌效果比超声 + 万古霉素更显著（P <.001）。在扫描电子显微镜下，暴露于超声 + 微泡 + 万古霉素的生物膜厚度和细菌密度的降低比其他治疗组更明显。组织病理学检查显示器官和皮肤无异常。
超声微泡增强了万古霉素对体内表皮葡萄球菌生物膜的抗菌效果，且未对动物造成明显损害。
