Induction of lethal infection with indigenous Escherichia coli in mice by fluorouracil

A single administration of fluorouracil (5-FU), a well-used cancer chemotherapeutic agent, at high doses (338-800 mg/kg) to specific pathogen free mice induced a lethal infection with Escherichia coli. The infection was manifested in all the mice treated with 5-FU 7-14 days after administration of the drug, when the number of E. coli in liver reached levels ranging from 10⁸ to 10¹⁰ colony-forming units, and the type of the infecting bacteria was limited to E. coli. The infection was accompanied with the increase in the population levels of E. coli in the intestinal tract which reached levels about 10³ to 10⁴ times as high as those of normal mice. Administration of tegafur, a less toxic derivative of 5-FU, to mice at a lethal dose of 1280 mg/kg induced infection with E. coli similar to that induced by 5-FU. Multiple administration of both streptomycin sulfate and cephalothin to mice after treatment with 5-FU protected the mice completely from the lethal infection induced by 5-FU, suggesting that the lethality of 5-FU was due to the indigenous bacterial infection.