BackgroundEnterococcus faecalis(E. faecalis) is frequently isolated from root canals with failed root canal treatments. Due to the strong ability ofE. faecalisto resist many often-used antimicrobials, coping withE. faecalisinfections remains a challenge. The aim of this study was to investigate the synergistic antibacterial effect of low-dose cetylpyridinium chloride (CPC) and silver ions (Ag+) againstE. faecalis in vitro.MethodsThe minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and the fractional inhibitory concentration index (FICI) were used to confirm the existence of the synergic antibacterial activity between low-dose CPC and Ag+. Colony-forming unit (CFU) counting, time-killing curve and dynamic growth curve were used to evaluate the antimicrobial effects of CPC and Ag+combinations against planktonicE. faecalis. Four weeks biofilms were treated with drug-contained gels to determine the antimicrobial effect on biofilm-residentE.faecalis, and the integrity ofE.faecalisand its biofilms were observed by FE-SEM. CCK-8 assays was used to test the cytotoxicity of CPC and Ag+combinations on MC3T3-E1 cells.ResultsThe results confirmed the synergistic antibacterial effect of low-dose CPC and Ag+against both planktonic and 4-week biofilmE. faecalis. After the addition of CPC, the sensitivity of both planktonic and biofilm-residentE. faecalisto Ag+improved, and the combination showed good biocompatibility on MC3T3-E1 cells.ConclusionsLow-dose CPC enhanced the antibacterial ability of Ag+against both planktonic and biofilmE.faecaliswith good biocompatibility. It may be developed into a novel and potent antibacterial agent againstE.faecalis, with low toxicity for root canal disinfection or other related medical applications.