Synergistic Effects of Bismuth Thiols and Various Antibiotics Against Pseudomonas aeruginosa Biofilm

BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen that takes advantages of some weaknesses in the immune system to initiate an infection. Biofilms of P. aeruginosa can cause chronic opportunistic infections in immunocompromised and elderly patients. This bacterium is considered as a model organism to study antibiotic resistance as well as biofilm formation. In the biofilm structures, bacteria are protected from many harmful environmental factors such as fluctuations in the level of oxygen and nutrients, and the alterations of pH as well as sensitivity to antibiotics. Decreased permeability of biofilms is one of the important reasons of antimicrobial resistance in bacteria. OBJECTIVES: In this study the anti-biofilm activity of bismuth thiols in combination with ciprofloxacin, imipenem and ceftazidime against the P. aeruginosa biofilm was investigated. MATERIALS AND METHODS: Checkerboard method was used to test the susceptibility of biofilms against various antimicrobial combinations. The biofilm formation was measured by 2,3-bis (2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide (XTT) colorimetric assay. The fractional bio-film inhibitory concentration was reported for each agent. RESULTS: The combination of bismuth ethanedithiol with ciprofloxacin showed synergistic inhibitory effect on the P. aeruginosa biofilm formation. The combination of bismuth ethanedithiol ciprofloxacin, ceftazidime and imipenem showed synergistic inhibitory effects on the biofilm formation. Furthermore, the combination of bismuth ethanedithiol, imipenem and ceftazidime did not show any synergistic inhibitory effect on biofilm formation. CONCLUSIONS: Our studies show that using appropriate concentrations of bismuth thiols in combination with various antibiotics can act synergistically against P. aeruginosa biofilm formation.