Development of a long-term ascending urinary tract infection mouse model for antibiotic treatment studies

A model of ascending unobstructed urinary tract infection (UTI) in mice was developed to study the significance of the antibiotic concentration in uri ne, serum, and kidney tissue for efficacy of treatment of UTI in general an d pyelonephritis in particular. Outbred Ssc-CF1 female mice were used throu ghout the study, and Escherichia coli was used as the pathogen. The virulen ce of 11 uropathogenic E. coli isolates and I nonpathogenic laboratory E. c oli strain was examined. Strain C175-94 achieved the highest counts in the kidneys, and this strain was subsequently used as the infecting organism. T he model gave reproducible bladder infections, i.e., bacteria were recovere d from 22 of 23 control mice after 3 days, and histological examination of kidney tissue shelved that of 14 infected kidneys, 7 (50%) showed major his tological changes, whereas 3 of 36 uninfected kidneys showed major histolog ical changes (P = 0.018). Once the model was established, the efficacies of different doses of cefuroxime and gentamicin, corresponding to active conc entrations in urine only or in urine, serum, and kidney tissue simultaneous ly, were examined. All cefuroxime doses resulted in significantly lower cou nts in urine than control treatments, but the dose which produced concentra tions of cefuroxime only in urine and not in serum or kidney tissue had no effect on kidney infection. Even low doses of gentamicin (0.05 mg/mouse) re sulted in concentrations in renal tissue for prolonged times due to accumul ation. All gentamicin doses had a significant effect (compared to the effec t of the control treatment) on bacterial counts in urine and kidneys. The a ntibiotic effect on bacterial counts In bladders was negligible for unknown reasons. Use of the mouse UTI model is feasible for study of the effect of an antibiotic in the urinary system, although the missing antibacterial ef fect in the bladder needs further evaluation.