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JAC Advance Access originally published online on April 12, 2008
Journal of Antimicrobial Chemotherapy 2008 62(1):35-40; doi:10.1093/jac/dkn147
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Reviews

Trimethoprim and enterococci in urinary tract infections: new perspectives on an old issue

Karin Tegmark Wisell1,*, Gunnar Kahlmeter2 and Christian G. Giske3

1 Department of Antibiotic Resistance and Hospital Hygiene, Swedish Institute for Infectious Disease Control, 17182 Solna, Sweden 2 Clinical Microbiology, Central Hospital, Växjö, Sweden 3 Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden

* Corresponding author. Tel: +46-8-457-2410; Fax: +46-8-301797; E-mail: karin.tegmark-wisell{at}smittskyddsinstitutet.se

The lack of oral treatment alternatives for enterococcal urinary tract infections (UTIs) has led to a renewed interest in trimethoprim. Enterococci can incorporate exogenously produced folates and thereby reverse the effect of trimethoprim. Although a large proportion of enterococci appear susceptible to trimethoprim in vitro using standard media devoid of folates, a 360-fold increase in the MIC can be seen when susceptibility testing is performed in media containing fresh urine. Even if trimethoprim has a favourable pharmacokinetic profile, with high serum and very high urine concentrations, pharmacodynamic (PD) estimates show that a large proportion of the apparent wild-type isolates (as categorized by standard susceptibility testing) have unfavourable PD indices. The clinical efficacy of trimethoprim in enterococcal UTI is debated. We could identify not more than 38 evaluable cases of enterococcal UTI in the literature. The eradication rate was 82%. Case reports where patients on co-trimoxazole for UTI have developed bacteraemia with enterococci susceptible to trimethoprim seem to support experimental findings that standard antimicrobial susceptibility testing poorly predicts the clinical outcome of trimethoprim therapy. The European Committee on Antimicrobial Susceptibility Testing and the national breakpoint committees in Europe have recently debated the role of trimethoprim in the treatment of enterococcal UTI and agreed to categorize wild-type enterococci as intermediate to trimethoprim and trimethoprim/sulfamethoxazole. This allows the distinction between enterococci with and without acquired resistance mechanisms to trimethoprim. This review discusses the microbiological, experimental, clinical and PD aspects of the usage of trimethoprim for enterococcal UTI.

Keywords: MIC , PK/PD , drug susceptibility testing , antimicrobial activity


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