ANTIBACTERIAL ACTIVITY OF SOME DERIVATIVES OF 7-AMINOCEPHALOSPORANIC ACID AGAINST STAPHYLOCOCCUS AUREUS AND SYNERGISM BETWEEN THESE AND OTHER ANTIBIOTICS.

The N-phenylacetyl derivative of 7-aminocephalosporanic acid (cephaloram) had roughly the same activity as benzylpenicillin against a number of Gram-positive organisms and about one-eighth of the activity of benzylpenicillin against penicillinsensitive strains of Staphylococcus aureus. This derivative and the N-alpha-phenoxypropionyl derivative of 7-aminocephalosporanic acid were 4 to 8 and 4 to 16 times as active as methicillin against penicillinase- and nonpenicillinase-producing staphylococcal strains, respectively. Neither the presence of horse serum nor changes in inoculum size appreciably affected the activities of any of the derivatives of 7-aminocephalosporanic acid which were tested. After forty-eight subcultures in the presence of antibiotic the increase in minimum inhibitory concentration against the staphylococcus was about four-times as great for cephaloram as for cephalosporin C. The resistant penicillinase-producing strains remained stable after six subcultures in antibiotic-free medium, and all the strains retained coagulase activity. Some degree of cross-resistance was found between the derivatives of 7-aminocephalosporanic acid and those of 6-aminopenicillanic acid. Synergism was observed in vitro between certain derivatives of 7-aminocephalosporanic acid and 6-aminopenicillanic acid when they were tested together or with fusidic acid or cephalosporin P(1) against a weak penicillinase-producing strain of Staphylococcus aureus. Cephalosporin C and cephalosporin C (pyridine), each in combination with benzylpenicillin, showed a significant degree of synergism in protection experiments in mice infected with a strong penicillinase-producing strain of Staphylococcus aureus.