Zhang Yunhui, Fu Yakun, Yu Jialin, Ai Qing, Li Junshuai, Peng Ningning, Song Sijie, He Yu, Wang Zhengli
Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China; Key Laboratory of Pediatrics in Chongqing, Chongqing, China; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China; Key Laboratory of Pediatrics in Chongqing, Chongqing, China; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
J Infect Chemother. 2015 Nov;21(11):808-15. doi: 10.1016/j.jiac.2015.08.017. Epub 2015 Sep 28.
Central venous catheters are widely used in neonatal intensive care units (NICUs) nowadays. The commonest cause of catheter-related bloodstream infections (CRBSIs) is coagulase-negative staphylococci (CoNS). Ambroxol, an active metabolite of bromhexine, exhibits antimicrobial activity against strains producing biofilm and enhances the bactericidal effect of some antibiotic by breaking the structure of biofilm. In this study, we aimed to determine the effect of ambroxol with vancomycin on the biofilm of Staphylococcus epidermidis (S. epidermidis) in vitro and in vivo. In the in vitro study, the biofilm of S. epidermidis was assessed by XTT reduction assay and analysed by confocal laser scanning microscopy (CLSM). In the in vivo study, a rabbit model of CRBSIs was created by intravenous intubation with a tube covered with S. epidermidis biofilm. The rabbits received one of the following four treatments by means of antibiotic lock therapy: normal heparin, ambroxol, vancomycin, or vancomycin plus ambroxol each for 3 days. The microstructure of the biofilm was assessed by scanning electron microscopy (SEM). The number of bacterial colonies in the organs (liver, heart, and kidney) and on the intravenous tubes was measured on agar plates. Pathological changes in the organs (liver, heart, and kidney) were observed with Hematoxylin-Eosin staining. The ambroxol exhibits significant efficacy to potentiate the bactericidal effect of vancomycin on S. epidermidis biofilm both in vitro and in vivo. The antibiotic lock therapy using a combination of ambroxol and vancomycin reveals a high ability to eradicate S. epidermidis biofilms in vivo. These results provide the basis of a useful anti-infection strategy for the treatment of CRBSIs.
中心静脉导管目前在新生儿重症监护病房（NICUs）中广泛使用。导管相关血流感染（CRBSIs）最常见的原因是凝固酶阴性葡萄球菌（CoNS）。氨溴索是溴己新的活性代谢产物，对产生生物膜的菌株具有抗菌活性，并通过破坏生物膜结构增强某些抗生素的杀菌效果。在本研究中，我们旨在确定氨溴索与万古霉素联合使用对表皮葡萄球菌（S. epidermidis）生物膜在体外和体内的影响。在体外研究中，通过XTT还原试验评估表皮葡萄球菌的生物膜，并通过共聚焦激光扫描显微镜（CLSM）进行分析。在体内研究中，通过静脉插管覆盖表皮葡萄球菌生物膜建立CRBSIs兔模型。兔子通过抗生素封管疗法接受以下四种治疗之一：普通肝素、氨溴索、万古霉素或万古霉素加氨溴索，各治疗3天。通过扫描电子显微镜（SEM）评估生物膜的微观结构。在琼脂平板上测量器官（肝脏、心脏和肾脏）和静脉导管上的细菌菌落数量。用苏木精-伊红染色观察器官（肝脏、心脏和肾脏）的病理变化。氨溴索在体外和体内均显示出显著增强万古霉素对表皮葡萄球菌生物膜杀菌效果的功效。使用氨溴索和万古霉素联合的抗生素封管疗法在体内显示出高清除表皮葡萄球菌生物膜的能力。这些结果为治疗CRBSIs提供了一种有效的抗感染策略的基础。
