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

Br J Pharmacol Chemother. 1964 Feb;22(1):22-33. doi: 10.1111/j.1476-5381.1964.tb01540.x.

Abstract

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.

MeSH terms

  • Animals
  • Anti-Bacterial Agents*
  • Antibiotics, Antitubercular*
  • Cephalosporins*
  • Coagulase*
  • Drug Resistance*
  • Drug Resistance, Microbial*
  • Fusidic Acid*
  • Methicillin*
  • Mice
  • Penicillanic Acid*
  • Penicillin G*
  • Penicillinase*
  • Pharmacology*
  • Research*
  • Staphylococcal Infections*
  • Staphylococcus aureus*
  • Staphylococcus*

Substances

  • Anti-Bacterial Agents
  • Antibiotics, Antitubercular
  • Cephalosporins
  • Coagulase
  • cephalosporin C
  • Fusidic Acid
  • Penicillanic Acid
  • 7-aminocephalosporanic acid
  • Penicillinase
  • cefaloram
  • Penicillin G
  • Methicillin
  • aminopenicillanic acid