title: 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.affiliation: Centre de Recherches, Roussel-Uclaf, Romainville, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Chantot
authors.forename: M
authors.initials: M
authors.lastname: Klich
authors.forename: G
authors.initials: G
authors.lastname: Teutsch
authors.forename: A
authors.initials: A
authors.lastname: Bryskier
authors.forename: P
authors.initials: P
authors.lastname: Collette
authors.forename: A
authors.initials: A
authors.lastname: Markus
authors.forename: G
authors.initials: G
authors.lastname: Seibert
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism; D003470:Culture Media; D029968:Escherichia coli Proteins; D006602:Hexosyltransferases; D008826:Microbial Sensitivity Tests; D008997:Monobactams / Q000494:pharmacology*; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D046928:Peptidoglycan Glycosyltransferase; D010458:Peptidyl Transferases; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D003470:Culture Media; D029968:Escherichia coli Proteins; C478704:FtsI protein, E coli; D008997:Monobactams; D046915:Penicillin-Binding Proteins; C077156:RU 44790; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D046928:Peptidoglycan Glycosyltransferase; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases