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. 1994 Apr;38(4):767–772. doi: 10.1128/aac.38.4.767

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

D J Payne 1, R Cramp 1, D J Winstanley 1, D J Knowles 1
PMCID: PMC284540  PMID: 8031044

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.

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Selected References

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  1. Aronoff S. C., Jacobs M. R., Johenning S., Yamabe S. Comparative activities of the beta-lactamase inhibitors YTR 830, sodium clavulanate, and sulbactam combined with amoxicillin or ampicillin. Antimicrob Agents Chemother. 1984 Oct;26(4):580–582. doi: 10.1128/aac.26.4.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bauernfeind A., Hörl G. Novel R-factor borne beta-lactamase of Escherichia coli confering resistance to cephalosporins. Infection. 1987 Jul-Aug;15(4):257–259. doi: 10.1007/BF01644127. [DOI] [PubMed] [Google Scholar]
  3. Bush K. Characterization of beta-lactamases. Antimicrob Agents Chemother. 1989 Mar;33(3):259–263. doi: 10.1128/aac.33.3.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bush K., Macalintal C., Rasmussen B. A., Lee V. J., Yang Y. Kinetic interactions of tazobactam with beta-lactamases from all major structural classes. Antimicrob Agents Chemother. 1993 Apr;37(4):851–858. doi: 10.1128/aac.37.4.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coleman K., Griffin D. R., Page J. W., Upshon P. A. In vitro evaluation of BRL 42715, a novel beta-lactamase inhibitor. Antimicrob Agents Chemother. 1989 Sep;33(9):1580–1587. doi: 10.1128/aac.33.9.1580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dale J. W., Smith J. T. R-factor-mediated beta-lactamases that hydrolyze oxacillin: evidence for two distinct groups. J Bacteriol. 1974 Aug;119(2):351–356. doi: 10.1128/jb.119.2.351-356.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Deschaseaux M. L., Jouvenot M., Adessi G. L., Michel-Briand Y. Two presumed novel beta-lactamases in members of the family Enterobacteriaceae. J Antimicrob Chemother. 1988 Jan;21(1):133–135. doi: 10.1093/jac/21.1.133-a. [DOI] [PubMed] [Google Scholar]
  8. Eliasson I., Kamme C. Characterization of the plasmid-mediated beta-lactamase in Branhamella catarrhalis, with special reference to substrate affinity. J Antimicrob Chemother. 1985 Feb;15(2):139–149. doi: 10.1093/jac/15.2.139. [DOI] [PubMed] [Google Scholar]
  9. Furth A. J. Purification and properties of a constitutive beta-lactamase from Pseudomonas aeruginosa strain Dalgleish. Biochim Biophys Acta. 1975 Feb 19;377(2):431–443. doi: 10.1016/0005-2744(75)90323-x. [DOI] [PubMed] [Google Scholar]
  10. Gutmann L., Ferré B., Goldstein F. W., Rizk N., Pinto-Schuster E., Acar J. F., Collatz E. SHV-5, a novel SHV-type beta-lactamase that hydrolyzes broad-spectrum cephalosporins and monobactams. Antimicrob Agents Chemother. 1989 Jun;33(6):951–956. doi: 10.1128/aac.33.6.951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gutmann L., Kitzis M. D., Billot-Klein D., Goldstein F., Tran Van Nhieu G., Lu T., Carlet J., Collatz E., Williamson R. Plasmid-mediated beta-lactamase (TEM-7) involved in resistance to ceftazidime and aztreonam. Rev Infect Dis. 1988 Jul-Aug;10(4):860–866. doi: 10.1093/clinids/10.4.860. [DOI] [PubMed] [Google Scholar]
  12. Hedges R. W., Datta N., Kontomichalou P., Smith J. T. Molecular specificities of R factor-determined beta-lactamases: correlation with plasmid compatibility. J Bacteriol. 1974 Jan;117(1):56–62. doi: 10.1128/jb.117.1.56-62.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jacobs M. R., Aronoff S. C., Johenning S., Shlaes D. M., Yamabe S. Comparative activities of the beta-lactamase inhibitors YTR 830, clavulanate, and sulbactam combined with ampicillin and broad-spectrum penicillins against defined beta-lactamase-producing aerobic gram-negative bacilli. Antimicrob Agents Chemother. 1986 Jun;29(6):980–985. doi: 10.1128/aac.29.6.980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jacoby G. A., Carreras I. Activities of beta-lactam antibiotics against Escherichia coli strains producing extended-spectrum beta-lactamases. Antimicrob Agents Chemother. 1990 May;34(5):858–862. doi: 10.1128/aac.34.5.858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jacoby G. A., Medeiros A. A. More extended-spectrum beta-lactamases. Antimicrob Agents Chemother. 1991 Sep;35(9):1697–1704. doi: 10.1128/aac.35.9.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jarlier V., Nicolas M. H., Fournier G., Philippon A. Extended broad-spectrum beta-lactamases conferring transferable resistance to newer beta-lactam agents in Enterobacteriaceae: hospital prevalence and susceptibility patterns. Rev Infect Dis. 1988 Jul-Aug;10(4):867–878. doi: 10.1093/clinids/10.4.867. [DOI] [PubMed] [Google Scholar]
  17. Kitzis M. D., Billot-Klein D., Goldstein F. W., Williamson R., Tran Van Nhieu G., Carlet J., Acar J. F., Gutmann L. Dissemination of the novel plasmid-mediated beta-lactamase CTX-1, which confers resistance to broad-spectrum cephalosporins, and its inhibition by beta-lactamase inhibitors. Antimicrob Agents Chemother. 1988 Jan;32(1):9–14. doi: 10.1128/aac.32.1.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kliebe C., Nies B. A., Meyer J. F., Tolxdorff-Neutzling R. M., Wiedemann B. Evolution of plasmid-coded resistance to broad-spectrum cephalosporins. Antimicrob Agents Chemother. 1985 Aug;28(2):302–307. doi: 10.1128/aac.28.2.302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mathew A., Harris A. M., Marshall M. J., Ross G. W. The use of analytical isoelectric focusing for detection and identification of beta-lactamases. J Gen Microbiol. 1975 May;88(1):169–178. doi: 10.1099/00221287-88-1-169. [DOI] [PubMed] [Google Scholar]
  20. Medeiros A. A., Cohenford M., Jacoby G. A. Five novel plasmid-determined beta-lactamases. Antimicrob Agents Chemother. 1985 May;27(5):715–719. doi: 10.1128/aac.27.5.715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Neu H. C. Contribution of beta-lactamases to bacterial resistance and mechanisms to inhibit beta-lactamases. Am J Med. 1985 Nov 29;79(5B):2–12. doi: 10.1016/0002-9343(85)90123-8. [DOI] [PubMed] [Google Scholar]
  22. Payne D. J., Amyes S. G. Transferable resistance to extended-spectrum beta-lactams: a major threat or a minor inconvenience? J Antimicrob Chemother. 1991 Mar;27(3):255–261. doi: 10.1093/jac/27.3.255. [DOI] [PubMed] [Google Scholar]
  23. Payne D. J., Coleman K., Cramp R. The automated in-vitro assessment of beta-lactamase inhibitors. J Antimicrob Chemother. 1991 Nov;28(5):775–776. doi: 10.1093/jac/28.5.775. [DOI] [PubMed] [Google Scholar]
  24. Petit A., Sirot D. L., Chanal C. M., Sirot J. L., Labia R., Gerbaud G., Cluzel R. A. Novel plasmid-mediated beta-lactamase in clinical isolates of Klebsiella pneumoniae more resistant to ceftazidime than to other broad-spectrum cephalosporins. Antimicrob Agents Chemother. 1988 May;32(5):626–630. doi: 10.1128/aac.32.5.626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Petrocheilou V., Sykes R. B., Richmond M. H. Novel R-plasmid-mediated beta-lactamase from Klebsiella aerogenes. Antimicrob Agents Chemother. 1977 Jul;12(1):126–128. doi: 10.1128/aac.12.1.126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Quinn J. P., Miyashiro D., Sahm D., Flamm R., Bush K. Novel plasmid-mediated beta-lactamase (TEM-10) conferring selective resistance to ceftazidime and aztreonam in clinical isolates of Klebsiella pneumoniae. Antimicrob Agents Chemother. 1989 Sep;33(9):1451–1456. doi: 10.1128/aac.33.9.1451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sirot D., Chanal C., Labia R., Meyran M., Sirot J., Cluzel R. Comparative study of five plasmid-mediated ceftazidimases isolated in Klebsiella pneumoniae. J Antimicrob Chemother. 1989 Oct;24(4):509–521. doi: 10.1093/jac/24.4.509. [DOI] [PubMed] [Google Scholar]
  28. Sirot D., Sirot J., Labia R., Morand A., Courvalin P., Darfeuille-Michaud A., Perroux R., Cluzel R. Transferable resistance to third-generation cephalosporins in clinical isolates of Klebsiella pneumoniae: identification of CTX-1, a novel beta-lactamase. J Antimicrob Chemother. 1987 Sep;20(3):323–334. doi: 10.1093/jac/20.3.323. [DOI] [PubMed] [Google Scholar]
  29. Spencer R. C., Wheat P. F., Winstanley T. G., Cox D. M., Plested S. J. Novel beta-lactamase in a clinical isolate of Klebsiella pneumoniae conferring unusual resistance to beta-lactam antibiotics. J Antimicrob Chemother. 1987 Dec;20(6):919–921. doi: 10.1093/jac/20.6.919. [DOI] [PubMed] [Google Scholar]
  30. Thabaut A., Acar J., Allouch P., Arlet G., Berardi-Grassias L., Bergogne-Bérézin E., Brun Y., Buisson Y., Chabanon G., Cluzel R. Fréquence et distribution des bêta-lactamases chez 1,792 souches de Klebsiella pneumoniae isolées en France entre 1985 et 1988. Pathol Biol (Paris) 1990 May;38(5):459–463. [PubMed] [Google Scholar]
  31. Thomson K. S., Weber D. A., Sanders C. C., Sanders W. E., Jr Beta-lactamase production in members of the family Enterobacteriaceae and resistance to beta-lactam-enzyme inhibitor combinations. Antimicrob Agents Chemother. 1990 Apr;34(4):622–627. doi: 10.1128/aac.34.4.622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wiedemann B., Kliebe C., Kresken M. The epidemiology of beta-lactamases. J Antimicrob Chemother. 1989 Nov;24 (Suppl B):1–22. doi: 10.1093/jac/24.suppl_b.1. [DOI] [PubMed] [Google Scholar]

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