Exploring the effect of sequential antibiotic exposure in resistant Escherichia coli causing urinary tract infections: a proof of principle study

Abstract

As global rates of antibiotic resistance increase and the development of new antibiotics become more difficult and costly, it is important to explore alternative strategies to improve the effectiveness of existing antibiotics. Previous studies have shown that sequential exposure of Pseudomonas aeruginosa to two antibiotics can effectively kill the bacteria and reduce the likelihood of resistance developing. However, the potential of this sequential approach for the treatment of Escherichia coli infections has not been thoroughly investigated. In our study, we conducted a proof-of-principle study to determine whether sequential exposure to mecillinam and ciprofloxacin can overcome phenotypic resistance to one or both drugs. We found that when E. coli were treated with subinhibitory doses of mecillinam followed by ciprofloxacin, their growth was significantly inhibited compared to treatment with ciprofloxacin alone, suggesting that sequential antibiotic exposure may be a viable strategy for treating infections caused by resistant E. coli .