Therapeutic effect of SF-2103A, a novel carbapenem antibiotic, in combination with cefotaxime, cefoperazone and other cephalosporins.
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.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000378:metabolism; D015780:Carbapenems; D002438:Cefoperazone / Q000008:administration & dosage*; D002439:Cefotaxime / Q000008:administration & dosage*; D002511:Cephalosporins / Q000008:administration & dosage* / Q000378:metabolism; D004355:Drug Stability; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004927:Escherichia coli Infections / Q000188:drug therapy; D007700:Kinetics; D011512:Proteus Infections / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D065093:beta-Lactamase Inhibitors
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D002511:Cephalosporins; D065093:beta-Lactamase Inhibitors; D002438:Cefoperazone; C035072:pluracidomycin; D002439:Cefotaxime