show Abstracthide AbstractRecurrent cystitis is a common disease in women, mainly due to uropathogenic Escherichia coli (UPEC). For decades, typing methods now considered as obsolete suggested that relapse by the same clone is dominant over reinfection, most UPEC being otherwise fully susceptible to antibiotics. We aimed to update these data. Thanks to a prospective study over 17 months we recruited 323 women with cystitis. 251 of them had non-recurrent infection and 72 had recurrence, with 2 to 9 episodes per patient for a total of 131 UPEC isolates and 145 UPEC pairs at patient level. Phylogroups B2 (52.4%) and D (14.1%) were overall dominant, as expected due their particular urovirulence. CH typing identified 119 distinct profiles with no CH-type particularly associated with recurrence. Relapse was attested by CH-typing for only 30.6% (22 out of 72), with very diverse situations ranging from all episodes due to the same clone to alternating reinfections and relapses. Next-Generation Sequencing confirmed the clonality for all but one out the 145 UPEC pairs. Antibiotic resistance was common for recurrent cystitis isolates (only 25 [17.2%] out of 145 UPEC pairs were fully susceptible), allowing to predict UPEC clonality. Indeed, antibiotic susceptible profile matched with CH-typing for 104 (71.7%) pairs. Finally, we demonstrated a large genetic diversity among UPEC responsible for cystitis in women, even in case of recurrence for which reinfection appeared dominant over relapse. Recurrent cystitis appears to be a heterogeneous disease requiring tailored treatment and prevention.