After a nearly threefold drop in prescriptions for the antibiotic ciprofloxacin between 2015 and 2021, the rates of ciprofloxacin-resistant E. coli bacteria circulating in the community did not decline. In fact, a study of Seattle-area women over age 50 who had not taken any antibiotics for at least a year discovered that the incidence of gut-colonizing ciprofloxacin-resistant E. coli actually increased. About 1 in 5 women in the study were affected. The results are consistent with theoretical models indicating that, once a drug-resistant form of E.coli emerges, it will continue to spread by taking up long-term residence in individuals’ gut microbiomes. Antibiotic resistant E. coli in the gut is of concern because the bacteria can enter the urinary tract and cause difficult-to-treat infections, particularly in women. Evidence from studies such as this one may be changing paradigms on how to fight the rise in antibiotic resistance.