Background: The aim of this study was to investigate the synergistic effect of ciprofloxacin (CPFX) and fosfomycin (FOM) on CPFX-resistant Pseudomonas aeruginosa strains. Methods: The synergistic effect was evaluated using the fractional inhibitory concentration index, acute bactericidal effect and morphological observation. Results: In the fractional inhibitory concentration index experiments, the combination of CPFX with FOM showed a synergistic effect in 20 of 74 (27.0%) strains of P. aeruginosa. From the morphological observations, it was determined that CPFX affected the outer membrane structure. CPFX combined with FOM caused striking morphological changes, resulting in bacteriolysis. A time lag experiment suggested that the addition of CPFX prior to FOM produced more pronounced bactericidal activity than the addition of FOM prior to CPFX. Conclusions: These results indicate that the combination of CPFX with FOM induces a synergistic effect on CPFX-resistant P. aeruginosa strains. The role of CPFX is thought to be related to damage of the outer membrane, enhancing FOM penetration.
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