In vitro activity of biofilm inhibitors in combination with antibacterial drugs against extensively drug-resistant Acinetobacter baumannii

Acinetobacter baumannii is a common pathogen of nosocomial infection, and its ability to form biofilms further contributes to its virulence and multidrug resistance, posing a great threat to global public health. In this study, we investigated the inhibitory effects of five biofilm inhibitors (BFIs) (zinc lactate, stannous fluoride, furanone, azithromycin, and rifampicin) on biofilm formation of nine extensively drug-resistant A. baumannii (XDRAB), and assessed the synergistic antibacterial effects of these BFIs when combined with one of four conventional anti-A. baumannii antibiotics (imipenem, meropenem, tigecycline, and polymyxin B). Each of the five BFIs tested was found to be able to significantly inhibit biofilm formation of all the clinical isolates tested under sub-minimal inhibitory concentrations. Then, we observed synergistic effects (in 22%, 56% and 11% of the isolates) and additive effects (56%, 44% and 44%) when zinc lactate, stannous fluoride and furanone were combined with tigecycline, respectively. When zinc lactate and stannous fluoride were each used with a carbapenem (imipenem or meropenem), in 33% and 56-67% of the isolates, they showed synergistic and additive effects, respectively. Additivity in > 50% of the isolates was detected when rifampicin was combined with imipenem, meropenem, tigecycline, or polymyxin B; and a 100% additivity was noted with azithromycin-polymyxin B combination. However, antagonism and indifference were noted for polymyxin B in its combination with zinc lactate and stannous fluoride, respectively. In conclusion, five BFIs in combination with four antibacterial drugs showed different degrees of in vitro synergistic and additive antibacterial effects against XDRAB.