Comparative therapeutic activities of ciprofloxacin, amoxicillin, ceftriaxone and co-trimoxazole in a new model of experimental infection with Escherichia coli.

A new mouse model for systemic infection with Escherichia coli is presented. Whereas in other models 10(7)-10(8) bacteria have to be injected into an animal to induce toxic effects resulting in death within 24 hours, now, only 10(3)-10(4) bacteria of an appropriate strain are required to produce a genuine infection characterized by an increase in the bacterial load over several days. The quantitative determination of bacterial counts per liver allows a more sensitive measurement than recording death rates. Furthermore, few animals are required for a definite result in contrast to the LD50 determination of other models. The salient point regarding this new model is that conditioning of animals has to be achieved by incorporating the inoculum into agar which is injected subcutaneously. The resulting infection is completely dependent on the E. coli strain used. Whereas a hemolytic, uropathogenic strain is so virulent that an overwhelming infection develops within 48 hours after the injection of 10(3) bacterial cells, a non-hemolytic variant of this strain is completely avirulent, being unable to multiply in spite of the potentiating agar. The hemolytic E. coli strain ATCC 25922 is intermediate in virulence. The bacterial counts per liver increase steadily until death occurs five to seven days after the injection of 10(4) bacteria. This bacterial infection can be therapeutically influenced by daily treatment with various drugs. Ciprofloxacin, ceftriaxone and co-trimoxazole are able to cure the infection, whereas amoxicillin given orally is only moderately active against this ATCC strain, which is relatively resistant to amoxicillin.