Trimethoprim Used for Selective Decontamination of the Digestive Tract in Rats: Possible Route of Excretion

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Abstract
Selective elimination of Enterobacteriaceae species from the digestive tract of rats has been accomplished by oral treatment with trimethoprim (235 mg/kg body weight/day) within 6 days. In the present study it was investigated whether this elimination was mainly due to antimicrobial activity of trimethoprim excreted with the gastrointestinal mucus or mainly by non-absorbed trimethoprim in the lumen contents. By means of whole gut irrigation (WGI) the lumen contents were washed out, followed by mucosa-associated flora. The concentration of the mucosa-associated Enterobacteriaceae remained at least 101/ml as measured in the last samples of rectal effluent during WGI in untreated rats. During trimethoprim treatment, however, the amount of mucosa-associated Enterobacteriaceae had decreased significantly more (p<0.05) compared with the Enterobacteriaceae present in the lumen contents of the gastrointestinal tract (photospectrometrically measured by the color of the rectal effluent). No difference was observed in the concentration of mucosa-associated enterococci in the rectal effluent of trimethoprim treated and untreated rats. It is concluded that orally administered trimethoprim may be predominantly active against Enterobacteriaceae associated with the mucous blanket.