Comparative activities of clavulanic acid, sulbactam, and tazobactam against clinically important beta-lactamases

Antimicrob Agents Chemother. 1994 Apr;38(4):767-72. doi: 10.1128/AAC.38.4.767.

Abstract

Clavulanic acid, sulbactam, and tazobactam are inhibitors of a variety of plasmid-mediated beta-lactamases. However, inhibition data for these three inhibitors with a wide range of different plasmid-mediated beta-lactamases have not yet been compared under the same experimental conditions. A number of groups have inferred that clavulanic acid inhibits extended-spectrum TEM and SHV beta-lactamases, but inhibition data have rarely been published. In this study, the 50% inhibitory concentrations of these three beta-lactamase inhibitors for 35 plasmid-mediated beta-lactamases have been determined. Of these 35 beta-lactamases, 20 were extended-spectrum TEM- or SHV-derived beta-lactamases. The other 15 enzymes were conventional-spectrum beta-lactamases such as TEM-1 and SHV-1. Clavulanic acid was a more potent inhibitor than sulbactam for 32 of the 35 plasmid-mediated beta-lactamases tested. In particular, clavulanic acid was 60 and 580 times more potent than sulbactam against TEM-1 and SHV-1, respectively, currently the two most clinically prevalent gram-negative plasmid-mediated beta-lactamases. Statistical analysis of the data of the 50% inhibitory concentrations showed that clavulanic acid was 20 times more active overall than sulbactam against the conventional-spectrum enzymes. In addition, clavulanic acid was 14 times more potent than sulbactam at inhibiting the extended-spectrum enzymes. Tazobactam also showed significantly greater activity than sulbactam against the two groups of beta-lactamases. There were no significant differences between the overall activities of tazobactam and clavulanic acid against the extended-spectrum TEM and SHV enzymes and conventional-spectrum enzymes, although differences in their inhibition profiles were observed.

Publication types

  • Comparative Study

MeSH terms

  • Bacteria / drug effects
  • Bacteria / enzymology
  • Bacteria / genetics
  • Clavulanic Acid
  • Clavulanic Acids / pharmacology*
  • Penicillanic Acid / analogs & derivatives*
  • Penicillanic Acid / pharmacology
  • Plasmids
  • Sulbactam / pharmacology*
  • Tazobactam
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / chemistry
  • beta-Lactamases / genetics

Substances

  • Clavulanic Acids
  • beta-Lactamase Inhibitors
  • Clavulanic Acid
  • Penicillanic Acid
  • beta-Lactamases
  • Sulbactam
  • Tazobactam