Studies on the synergism of sulbactam and beta-lactam antibiotics under in vitro conditions and in healthy volunteers after intravenous administration. Antibacterial activity in vitro, compatibility and pharmacokinetics of the drugs in combination.
Sulbactam, a new beta-lactam inhibitor, increased the in vitro activity of cefotaxime, mezlocillin and piperacillin against 803 clinical bacterial isolates. The synergism of sulbactam and these antibiotics was particular marked against 467 beta-lactamase positive strains, both aerobic and anaerobic. In the presence of sulbactam the mean minimal inhibitory concentrations (MICs) of the antibiotics against beta-lactamase positive bacteria were greatly reduced: with cefotaxime by 58%, with mezlocillin by 64% and with piperacillin by 70%. Sulbactam alone at low concentrations inhibited the growth of only a few strains (Neisseria spp., Acinetobacter spp.). The inhibitor proved to be very stable in infusion media under a variety of conditions and was compatible in vitro with 14 different beta-lactam antibiotics. The pharmacokinetics profiles of sulbactam and the antibiotics cefotaxime, mezlocillin and piperacillin were similar after infusion to healthy volunteers. The relevant pharmacokinetic parameters of the single substances were essentially unchanged when administered in combination. The general similarity between the pharmacokinetics of sulbactam and of the beta-lactam antibiotics appears to be an essential precondition for the therapeutic success of such a synergistic combination. Thus the physicochemical and pharmacological properties of sulbactam apparently permit flexible dosage in combination with different penicillins or cephalosporins and sulbactam can be administered as non-fixed combination in the clinical treatment of bacterial infections.
Wildfeuer
A
A
Research and Development Division, Pfizer/Mack, Illertissen, Fed. Rep. of Germany.
Schmalreck
A
A
Räder
K
K
Eibel
G
G
Pfaff
G
G
D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001419:Bacteria / Q000187:drug effects / Q000201:enzymology; D002439:Cefotaxime / Q000494:pharmacology; D004357:Drug Synergism; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008802:Mezlocillin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010878:Piperacillin / Q000494:pharmacology; D013407:Sulbactam / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001618:beta-Lactamases / Q000032:analysis
D000900:Anti-Bacterial Agents; D001618:beta-Lactamases; D002439:Cefotaxime; D008802:Mezlocillin; D013407:Sulbactam; D010878:Piperacillin