title: Synergy of ambroxol with vancomycin in elimination of catheter-related Staphylococcus epidermidis biofilm in vitro and in vivo.
abstract: 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.
authors.affiliation: 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.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yakun
authors.initials: Y
authors.lastname: Fu
authors.affiliation: 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. Electronic address: yujialin486@126.com.
authors.forename: Jialin
authors.initials: J
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ai
authors.affiliation: 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.
authors.forename: Junshuai
authors.initials: J
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Ningning
authors.initials: N
authors.lastname: Peng
authors.affiliation: 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.
authors.forename: Sijie
authors.initials: S
authors.lastname: Song
authors.affiliation: 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.
authors.forename: Yu
authors.initials: Y
authors.lastname: He
authors.affiliation: 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.
authors.forename: Zhengli
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000551:Ambroxol / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D055499:Catheter-Related Infections / Q000382:microbiology*; D004357:Drug Synergism; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D011817:Rabbits; D013203:Staphylococcal Infections / Q000382:microbiology*; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000551:Ambroxol; D014640:Vancomycin
keywords: Ambroxol; Antibiotic lock therapy; Biofilm; Staphylococcus epidermidis; Vancomycin