Resistance to
antibiotics used for the treatment of
urinary tract infections (UTIs) is increasing worldwide. The impact of in vitro resistance on clinical outcome in UTIs requires further study, since most studies of both humans and animals have evaluated only the efficacy of
antibiotics toward bacteria susceptible in vitro. We were interested in evaluating the relationship between the in vitro antibacterial effect and the in vivo efficacy after
antibiotic treatment. We simulated a natural ascending UTI by use of the ascending UTI mouse model and used Escherichia coli strains with various susceptibilities to
amdinocillin (
mecillinam) and
sulfamethizole. Mice were treated for 3 days with
antibiotic doses approximating human urinary tract concentrations after a standard oral dose. For a susceptible strain (MIC, 0.5 micro g/ml) and a resistant strain (MIC, 128 micro g/ml), respectively, there were significant reductions in bacterial counts in the urine, bladder, and kidneys
after treatment with
amdinocillin, whereas for a strain for which the MIC was 16 micro g/ml, there was a significant reduction in bacterial counts in the kidneys only (P < 0.05). Treatment with
sulfamethizole resulted in a significant reduction in bacterial counts in all samples from a susceptible strain (MIC, 128 micro g/ml) and a resistant strain (MIC, 512 micro g/ml).
Infection with a sulII gene-positive strain (MIC, >2,048 micro g/ml) could not be treated with
sulfamethizole, as no effect could be demonstrated in the urine, bladder, or kidneys. For
amdinocillin, there was no clear-cut relationship between the in vitro susceptibility and the in vivo outcome, while for
sulfamethizole, we found a relationship between the MIC for the strain and the effect in the urinary tract.