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

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.

• Authors: J F Chantot, M Klich, G Teutsch, A Bryskier, P Collette, A Markus, G Seibert
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 36 Issue 8 Pg. 1756-63 (Aug 1992) ISSN: 0066-4804 [Print] United States
• PMID: 1416860 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Bacterial Agents
• Bacterial Proteins
• Carrier Proteins
• Culture Media
• Escherichia coli Proteins
• FtsI protein, E coli
• Monobactams
• Penicillin-Binding Proteins
• RU 44790
• Peptidyl Transferases
• Hexosyltransferases
• Peptidoglycan Glycosyltransferase
• Muramoylpentapeptide Carboxypeptidase
• beta-Lactamases

Topics

• Anti-Bacterial Agents (pharmacology)
• Bacteria (drug effects, enzymology)
• Bacterial Proteins
• Carrier Proteins (metabolism)
• Culture Media
• Escherichia coli Proteins
• Hexosyltransferases
• Microbial Sensitivity Tests
• Monobactams (pharmacology)
• Muramoylpentapeptide Carboxypeptidase (metabolism)
• Penicillin-Binding Proteins
• Peptidoglycan Glycosyltransferase
• Peptidyl Transferases
• beta-Lactamases (metabolism)