The alarming increase in rates of bacterial antimicrobial resistance in the past decade has now escalated to what is globally recognised as a public health crisis. The prospect of being left with no effective antibiotics to treat and prevent common human infections, such as urinary tract infections (UTIs) and sepsis, is now a reality for several parts of the world and a looming threat to Australia’s public health. There is an urgent need for effective therapies against multidrug resistant pathogens and the infections they cause. A promising new direction in the field involves the development of alternative therapeutics that target bacterial virulence (antivirulence) instead of viability (antibiotics). In this presentation I will describe the potential of recently developed anti-adhesion compounds as alternative therapeutics for UTIs caused by a recently emerged global clone of multidrug resistant E. coli (Sequence Type 131, ST131). Our studies showed that oral inhibitors of the FimH adhesin, a key colonization factor of E. coli ST131, were effective in preventing infection in mice experimentally inoculated with E. coli ST131 unlike prophylactic administration of oral antibiotics. Moreover, small doses of orally administered anti-adhesion compounds significantly decreased the high E. coli ST131 burden established in the bladder of mice with chronic UTIs. Taken together, our results offer promise for the therapeutic potential of anti-adhesion and antivirulence compounds in preventing and treating E. coli infections otherwise refractory to empirically prescribed ‘off-the-shelf’ antibiotics.