In Vivo Synergy Between 6β-Amidinopenicillanic Acid Derivatives and Other Antibiotics

Both an oral and a parenteral form of a 6β-amidinopenicillanic acid derivative were found to have appreciable activity against gram-negative bacteria and poor activity against gram-positive bacteria in vivo. When administered orally or parenterally, definite synergy was demonstrated between the amidinopenicillins and ampicillin, amoxicillin, benzylpenicillin, cefazolin, or carbenicillin in infections with a number of gram-negative bacteria, includingKlebsiella, Enterobacter, Escherichia, Proteus, Salmonella , andHaemophilus species in mice. Synergy was also observed between the parenteral amidinopenicillin and benzylpenicillin in theStaphylococcus aureus infection but not in infections with other gram-positive organisms. No synergy was demonstrated between the parenteral amidinopenicillin and erythromycin or oxytetracycline in infections with gram-positive or gram-negative organisms. Synergy between the parenteral amidinopenicillin and gentamicin was observed only in the case ofEscherichia coli .