pluracidomycin and Escherichia-coli-Infections

Combinations of SF-2103A with cefotaxime, cefoperazone or cefazolin showed synergistic efficacy at a wide range of combination ratios against experimental infection in mice due to Proteus vulgaris GN76/C-1, producing type Ic cephalosporinase, Escherichia coli No. 29/36 RGN823, producing type IIIa (TEM-2) penicillinase and E. coli GN206, producing type Ib cephalosporinase. These effects by SF-2103A were greater than those seen with sulbactam. The in vitro and in vivo synergistic activities were roughly correlated. Potent in vivo activity of SF-2103A was related to good pharmacokinetic properties, with blood half-life of 30 minutes and urinary recovery of 55.2% after parenteral administration to rats. Furthermore, SF-2103A was stable to rat kidney homogenate. The high stability of SF-2103A in aqueous and biological media was correlated with the sulfonate group at C-3.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Carbapenems; Cefoperazone; Cefotaxime; Cephalosporins; Drug Stability; Drug Synergism; Drug Therapy, Combination; Escherichia coli Infections; Kinetics; Proteus Infections; Rats; Rats, Inbred Strains; Structure-Activity Relationship