Synergy Of Ambroxol With Vancomycin In Elimination Of Catheter-Related Staphylococcus Epidermidis Biofilm In Vivo

[Objective] To establish rabbit model of catheter-related bloodstream infection(CRBSI) caused by Staphylococcus epidermidis with biofilm(BF)formation, further to investigate the synergy of ambroxol with vancomycin in elimination of catheter-related S.epidermidis RP62 A strain’s biofilm in the complex environment in vivo.[Methods] A rabbit model of CRBSI 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: noemal heparin, ambroxol, vancomycin, or ambroxol plus vancomycin each for 3 days. The number of bacterial colonies in the organs(liver, heart, and kidney) and on the intravenous tubes was measured on agar plates. The microstructure of the biofilm was assessed by scanning electron microscopy(SEM). Pathological changes in the organs(liver, heart,and kidney) were observed with Hematoxylin-Eosin staining.[Results] The rabbit model of CRBSI caused by S. epidermidis biofilm was successfully established. Bacterial counts on the inner surface of catheter were: control group7.02(6.56-7.80)/ml, ambroxol group6.41(6.32-6.83)/ml, vancomycin group4.30(0-4.90)/ml, ambroxolplus vancomycin group0(0-2.25)/ml. Bacerial counts in the heart: control group 2.34(2.20-2.45)/ml, ambroxol group 1.76(1.47-2.00)/ml, vancomycin group 1.21(1.04-1.63)/ml, ambroxol plus vancomycin group0.45(0-1.24)/ml. Bacerial counts in the liver: control group3.00(2.81-3.07)/ml, ambroxol group2.49(2.30-2.66)/ml, vancomycin group1.02(0-1.12)/ml, ambroxol plus vancomycin group 0(0-0.22)/ml.Bacerial counts in the heart: control group2.11(2.00-2.24)/ml, ambroxol group1.30(1.01-1.60)/ml, vancomycin group1.05(0.41-1.14)/ml, ambroxol plus vancomycin group 0(0-0.35)/ml. Compared to the control group,ambroxol achieved a significant reduction of CFU(P<0.05). In the ambroxol group, the biofilm had a less fibrous structure with a cracked tile-like pattern compared with the control group. However, there were no biofilm visualized and only sporadic bacteria were detected on the inner surface of catheters in the group treated with vancomycin plus ambroxol.All the histopathological changes in heart, liver and kidney tissues were mildest in the vancomycin plus ambroxol group.[Conclusion] The ambroxol still exhibits efficacy to damage the structure of S.epidermidis biofilm and kill the bacterium in the S.epidermidis biofilm. The antibiotic lock therapy using a combination of ambroxol and vancomycin reveals a high ability to eradicate S.epidermidis biofilms, indicate that ambroxol can potentiate the bactericidal effect of vancomycin on S.epidermidis biofilm, and at the same time had thesynergistic effect.