Combination of 7-hydroxyflavone and colistin: antibacterial activity and mechanism against multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii

With the continuous escalation of resistance of Pseudomonas aeruginosa and Acinetobacter baumannii to first line antibiotics such as colistin (COL), the development of novel therapeutic strategies is urgently required. This study demonstrates for the first time that 7-hydroxyflavone (7-HF) can restore COL’s bactericidal activity against clinically resistant Pseudomonas aeruginosa and Acinetobacter baumannii, and the synergistic effect of 7-HF combined with COL was confirmed by both checkerboard and time-kill curves. The anti-biofilm effect of COL combined with 7-HF was evaluated by biofilm inhibition assay. Safety assessments, including cytotoxicity and erythrocyte hemolysis tests, indicated that both monotherapy and combination regimens were well-tolerated. In addition, the combined use of COL and 7-HF reduced the bacterial load in a mouse thigh infection model. Our findings may provide a clinically safe and effective strategy for combating multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii infections.