Development of a Long-Term Ascending Urinary Tract Infection Mouse Model for Antibiotic Treatment Studies

Abstract

A model of ascending unobstructed urinary tract infection (UTI) in mice was developed to study the significance of the antibiotic concentration in urine, serum, and kidney tissue for efficacy of treatment of UTI in general and pyelonephritis in particular. Outbred Ssc-CF1 female mice were used throughout the study, and Escherichia coli was used as the pathogen. The virulence of 11 uropathogenic E. coli isolates and 1 nonpathogenic laboratory E. coli strain was examined. Strain C175-94 achieved the highest counts in the kidneys, and this strain was subsequently used as the infecting organism. The model gave reproducible bladder infections, i.e., bacteria were recovered from 22 of 23 control mice after 3 days, and histological examination of kidney tissue showed that of 14 infected kidneys, 7 (50%) showed major histological changes, whereas 3 of 36 uninfected kidneys showed major histological changes (P ‫؍‬ 0.018). Once the model was established, the efficacies of different doses of cefuroxime and gentamicin, corresponding to active concentrations in urine only or in urine, serum, and kidney tissue simultaneously, were examined. All cefuroxime doses resulted in significantly lower counts in urine than control treatments, but the dose which produced concentrations 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) resulted in concentrations in renal tissue for prolonged times due to accumulation. All gentamicin doses had a significant effect (compared to the effect of the control treatment) on bacterial counts in urine and kidneys. The antibiotic 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 effect in the bladder needs further evaluation.Urinary tract infections (UTIs) are among the most commonly observed infections in clinical practice, and more than 25% of all women experience an UTI at least once during their lifetimes (6). The majority of UTIs are far from severe; i.e., they are not life-threatening and do not produce any irreversible damage. However, when the kidneys are involved in the infection, there is a risk of irreversible kidney tissue damage as well as an increased risk of bacteremia (6).Escherichia coli is the causative agent in about 85% of community-acquired UTIs, 50% of nosocomial UTIs, and more than 80% of cases of uncomplicated pyelonephritis (6, 35). Several virulence factors among uropathogenic strains of E. coli have been recognized, including different types of adhesins, serum resistance, iron sequestration, and hemolysin production (17,22,30,31).Treatments for cystitis are well documented, especially different strategies concerning short-term treatment with a number of antibiotics (15,21,28), while the documentation concerning the duration of treatment of pyelonephritis is poor (1, 6, 27), with the failure rate for the treatment of pyelon...

MarA, SoxS and Rob function as virulence factors in an Escherichia coli murine model of ascending pyelonephritis

“…1b). Similar findings of 'outliers' have also been observed with Proteus mirabilis UreR mutants (Dattelbaum et al, 2003), and when the model has been used to test antibiotics, including an aminoglycoside, a penicillin, a cephalosporin, or trimethoprim-sulfamethoxazole, to treat susceptible E. coli infection (Hvidberg et al, 2000;Kerrn et al, 2003;Schilling et al, 2002). Complete sterilization of any portion (urine, bladders or kidneys) of the mouse urinary tract has not been achieved in this model using genetic or therapeutic means (Dattelbaum et al, 2003;Hvidberg et al, 2000;Kerrn et al, 2003;Schilling et al, 2002).…”

“…The presence of bacteria within an otherwise sterile mouse kidney, nevertheless, correlates well with an active infection (Hvidberg et al, 2000). The model used in this study reports on the inability of E. coli deletion mutants to colonize the mouse kidney; colonization is a critical component required for most bacterial infections.…”

Prevalence and Antibiogram of Bacterial Uropathogens of Urinary Tract Infections from a Tertiary Care Hospital of Bangladesh

“…However, uncomplicated UTI may also occur in men because of insertive anal intercourse or lack of circumcision or having sexual partner with vaginal colonization with uropathogenic microorganisms or lack of immunity [20,21]. Though, majority of uncomplicated UTIs don't cause any threat to the lives and irreparable damage, still there is a risk of serious tissue damage with prevalence of bacteremia, when kidneys are involved [22]. In the present study, three age groups were formed to trace the distribution of uropathogens according to age (Fig.…”

Antimicrobial susceptibility test of pathogens isolated from urinary tract infection suspected cases

“…Infection due to Proteus spp is associated with renal stones while Staphylococcus saprophyticus infections are usually found in sexually active women. Majority of UTIs are not life threatening but when the kidneys are involved, there is risk of permanent tissue damage with an increased risk of bacteremia [6]. Neonates, girls, young women, and older men are mainly vulnerable to UTIs.…”