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Antimicrobial Agents and Chemotherapy, March 2003, p. 1002-1009, Vol. 47, No. 3
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.3.1002-1009.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Effects of Sulfamethizole and Amdinocillin against Escherichia coli Strains (with Various Susceptibilities) in an Ascending Urinary Tract Infection Mouse Model

M. B. Kerrn,* N. Frimodt-Møller, and F. Espersen

Department of Microbiological R & D, Statens Serum Institut, Copenhagen, Denmark

Received 29 January 2002/ Returned for modification 8 September 2002/ Accepted 19 November 2002

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.

* Corresponding author. Mailing address: Statens Serum Institut, Department of Microbiological R & D, Artillerivej 5, 2300 Copenhagen S, Denmark. Phone: 45 32683575. Fax: 45 32683887. E-mail: mbp{at}ssi.dk.

Antimicrobial Agents and Chemotherapy, March 2003, p. 1002-1009, Vol. 47, No. 3
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.3.1002-1009.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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