Affiliation:
1. Department of Microbiological R & D, Statens Serum Institut, Copenhagen, Denmark
Abstract
ABSTRACT
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 μg/ml) and a resistant strain (MIC, 128 μg/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 μg/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 μg/ml) and a resistant strain (MIC, 512 μg/ml). Infection with a
sulII
gene-positive strain (MIC, >2,048 μg/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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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