H. Hvidberg et al., Development of a long-term ascending urinary tract infection mouse model for antibiotic treatment studies, ANTIM AG CH, 44(1), 2000, pp. 156-163
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.