Comparative effects of amoxycillin and ampicillin on the morphology of Escherichia coli in vivo and correlation with activity.

An experimental mouse intraperitoneal infection due to Escherichia coli was treated with subcutaneous amoxycillin or ampicillin. Specimens of blood and peritoneal washings from the infected animals were assayed for antibiotic concentrations and examined microscopically for observation of the effects produced by the two penicillins on the morphology of bacteria growing in vivo. Amoxycillin was significantly more effective than ampicillin in protecting the animals from the lethal effects of the infection, although the antibiotic concentrations in the body fluids were very similar for both compounds. However, microscopic examination showed marked differences in the morphological effects produced at equivalent dose levels by the two compounds against the bacteria present in blood and peritoneal fluid. Treatment with amoxycillin at dose levels that produced peak antibiotic concentrations in the body fluids ranging from one-quarter to three times the minimum inhibitory concentration resulted in the formation of spheroplast forms, which lysed rapidly. In contrast, at the same concentrations, ampicillin produced relatively stable filaments or long cell forms, which lysed much more slowly, although at higher dose levels the effects produced were generally similar to those seen with amoxycillin. It is concluded that the superior therapeutic activity of amoxycillin compared with ampicillin is due to its greater bacteriolytic activity in vivo.