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. 1992 Aug;36(8):1756–1763. doi: 10.1128/aac.36.8.1756

Antibacterial activity of RU44790, a new N-tetrazolyl monocyclic beta-lactam.

J F Chantot 1, M Klich 1, G Teutsch 1, A Bryskier 1, P Collette 1, A Markus 1, G Seibert 1
PMCID: PMC192042  PMID: 1416860

Abstract

RU44790 belongs to a new class of synthetic monocyclic beta-lactam antibiotics which feature a bioisosteric tetrazole moiety instead of the more classical acidic functions at the N-1 position of the beta-lactam ring. Its antibacterial activity was evaluated against some 900 strains and was compared with those of other recent beta-lactam derivatives, especially aztreonam. RU44790 is endowed with potent activity against gram-negative bacteria. At less than or equal to 0.6 micrograms/ml, RU44790 inhibited 90% of all strains of the family Enterobacteriaceae with the exception of Citrobacter spp. (MIC for 90% of strains tested, 1.2 micrograms/ml). The activity was similar to that of aztreonam against strains that are normally susceptible to expanded-spectrum cephalosporins. On the other hand, the new compound was 10 to 100 times more potent than aztreonam and most of the other antibiotics tested against enterobacteria that produce chromosome-encoded or plasmid-mediated extended-spectrum beta-lactamases. Pseudomonas aeruginosa isolates were equally susceptible to both monobactams. RU44790 was inactive against staphylococci and had only marginal activity against streptococci (MIC for 50% of strains tested, 2.5 micrograms/ml). RU44790 was highly resistant to hydrolysis by various beta-lactamases, particularly cephalosporinases such as P99. The latter enzyme was also inhibited by the compound. RU44790 showed a high affinity for penicillin-binding protein 3 of Escherichia coli. The results suggest that RU44790 has good potential in the treatment of infections caused by gram-negative microorganisms.

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Selected References

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  1. 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]
  2. Bush K. Classification of beta-lactamases: groups 1, 2a, 2b, and 2b'. Antimicrob Agents Chemother. 1989 Mar;33(3):264–270. doi: 10.1128/aac.33.3.264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bush K. Classification of beta-lactamases: groups 2c, 2d, 2e, 3, and 4. Antimicrob Agents Chemother. 1989 Mar;33(3):271–276. doi: 10.1128/aac.33.3.271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Imada A., Kitano K., Kintaka K., Muroi M., Asai M. Sulfazecin and isosulfazecin, novel beta-lactam antibiotics of bacterial origin. Nature. 1981 Feb 12;289(5798):590–591. doi: 10.1038/289590a0. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Kishimoto S., Sendai M., Hashiguchi S., Tomimoto M., Satoh Y., Matsuo T., Kondo M., Ochiai M. Synthesis of sulfazecin-type 2-azetidinones with a carbon substituent at the 4-position. J Antibiot (Tokyo) 1983 Oct;36(10):1421–1424. doi: 10.7164/antibiotics.36.1421. [DOI] [PubMed] [Google Scholar]
  7. Neu H. C., Chin N. X. In vitro activity and beta-lactamase stability of a new monobactam, B0-1165. Antimicrob Agents Chemother. 1987 Apr;31(4):505–511. doi: 10.1128/aac.31.4.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Neu H. C., Chin N. X., Labthavikul P. The in-vitro activity and beta-lactamase stability of carumonam. J Antimicrob Chemother. 1986 Jul;18(1):35–44. doi: 10.1093/jac/18.1.35. [DOI] [PubMed] [Google Scholar]
  9. Nélet F., Gutmann L., Kitzis M. D., Acar J. F. Tigemonam activity against clinical isolates of Enterobacteriaceae and Enterobacteriaceae with known mechanisms of resistance to beta-lactam antibiotics. J Antimicrob Chemother. 1989 Aug;24(2):173–181. doi: 10.1093/jac/24.2.173. [DOI] [PubMed] [Google Scholar]
  10. O'Callaghan C. H., Muggleton P. W., Ross G. W. Effects of beta-lactamase from gram-negative organisms on cephalosporins and penicillins. Antimicrob Agents Chemother (Bethesda) 1968;8:57–63. [PubMed] [Google Scholar]
  11. Seibert G., Biebach A. Eine enzymatische Methode zur Bestimmung von Cefotaxim in Serum- und Harnproben. J Clin Chem Clin Biochem. 1981 May;19(5):279–281. [PubMed] [Google Scholar]
  12. Sykes R. B., Bonner D. P., Bush K., Georgopapadakou N. H., Wells J. S. Monobactams--monocyclic beta-lactam antibiotics produced by bacteria. J Antimicrob Chemother. 1981 Dec;8 (Suppl E):1–16. doi: 10.1093/jac/8.suppl_e.1. [DOI] [PubMed] [Google Scholar]
  13. Sykes R. B., Cimarusti C. M., Bonner D. P., Bush K., Floyd D. M., Georgopapadakou N. H., Koster W. M., Liu W. C., Parker W. L., Principe P. A. Monocyclic beta-lactam antibiotics produced by bacteria. Nature. 1981 Jun 11;291(5815):489–491. doi: 10.1038/291489a0. [DOI] [PubMed] [Google Scholar]
  14. Sykes R. B., Koster W. H., Bonner D. P. The new monobactams: chemistry and biology. J Clin Pharmacol. 1988 Feb;28(2):113–119. doi: 10.1002/j.1552-4604.1988.tb05734.x. [DOI] [PubMed] [Google Scholar]
  15. Tanaka S. K., Summerill R. A., Minassian B. F., Bush K., Visnic D. A., Bonner D. P., Sykes R. B. In vitro evaluation of tigemonam, a novel oral monobactam. Antimicrob Agents Chemother. 1987 Feb;31(2):219–225. doi: 10.1128/aac.31.2.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Yoshida C., Tanaka K., Nakano J., Todo Y., Yamafuji T., Hattori R., Fukuoka Y., Saikawa I. Studies on monocyclic beta-lactam antibiotics. III. Synthesis and antibacterial activity of N-(aromatic heterocyclic substituted)azetidin-2-ones. J Antibiot (Tokyo) 1986 Jan;39(1):76–89. doi: 10.7164/antibiotics.39.76. [DOI] [PubMed] [Google Scholar]
  17. Zurenko G. E., Truesdell S. E., Yagi B. H., Mourey R. J., Laborde A. L. In vitro antibacterial activity and interactions with beta-lactamases and penicillin-binding proteins of the new monocarbam antibiotic U-78608. Antimicrob Agents Chemother. 1990 May;34(5):884–888. doi: 10.1128/aac.34.5.884. [DOI] [PMC free article] [PubMed] [Google Scholar]

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