Urinary tract infection (UTI) is an extremely common infectious condition affecting people throughout the world. Increasing antibiotic resistance in pathogens causing UTI threatens our ability to continue to treat patients in the clinics.

AimTo test the effects of dapagliflozin‐induced hyperglucosuria on ascending bacterial urinary tract infection (UTI) in a mouse model.MethodsDapagliflozin or canagliflozin was used to induce hyperglucosuria in non‐diabetic adult female mice prior to transurethral inoculation with uropathogenic Escherichia coli (UPEC) or Klebsiella pneumoniae. Glucose, bacterial load, cytokines, neutrophil mobilization and inflammation during acute and chronic UTI were determined.ResultsSignificant increase in UPEC load was observed in the urinary tract of hyperglucosuric mice compared with controls. Dapagliflozin‐treated mice developed bacteraemia resulting in UPEC colonization of the spleen and liver at a higher frequency than controls. Chronic UTI in hyperglucosuric mice resulted in an increased incidence of renal abscesses. Histopathological evaluation revealed only modest increases in tissue damage in the urinary bladders and kidneys of dapagliflozin‐treated mice, despite a profound increase in bacterial load. There was poor neutrophil mobilization to the urine of hyperglucosuric mice. We also observed a delayed increase of IL‐1β in urine, and bladders, and IL‐6 in urine of hyperglucosuric mice. Experimental inoculation with K. pneumoniae also revealed higher bacterial burden in the urinary bladder, spleen and liver from dapagliflozin‐treated mice compared with controls.ConclusionCollectively, our results indicate that dapagliflozin‐induced hyperglucosuria in non‐diabetic female mice leads to increased susceptibility to severe UTI, and bacteraemia of urinary tract origin.

Urinary tract infection (UTI) is one of the most prevalent bacterial infections, particularly in women, children, and the elderly. Uropathogenic Escherichia coli (UPEC) is the predominant etiological agent of UTI.

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