[Antibacterial activity of sulopenem, a new parenteral penem antibiotic].
Sulopenem, a new penem antibiotic, was compared with other antibiotics with regard to in vitro antibacterial and bactericidal activities, stabilization against beta-lactamases, and effect on the release of lipopolysaccharide from Gram-negative bacteria. The results are summarized as follows. 1. Sulopenem showed more potent activities than other antibiotics against both Gram-positive and Gram-negative bacteria except Pseudomonas aeruginosa. 2. Sulopenem showed potent bactericidal activities (MIC/MBC) against both Gram-positive and Gram-negative bacteria. Time kill studies against Staphylococcus aureus, Escherichia coli, Enterobacter cloacae and Citrobacter freundii showed potent bactericidal activities of sulopenem. 3. Sulopenem was found to possess a stronger activity than other antibiotics against beta-lactamase-producing strains except P. aeruginosa and Stenotrophomonas maltophilia. 4. In particular, sulopenem was found to be more stable to the hydrolysis by various beta-lactamases produced by Gram-negative bacteria than any other antibiotics tested. Vmax/Km values of sulopenem were smaller than those of cefotiam for all tested beta-lactamases, which reflected a broad antibacterial spectrum of sulopenem. 5. E. coli ML4707 exposed to sulopenem and imipenem released less endotoxin than did controls at all concentration ranges tested. In contrast, the strain exposed to ceftazidime at bacteriostatic concentrations released a large amount of endotoxin.
Inoue
E
E
Epizome Institute, Gunma, Japan.
Komoto
E
E
Taniyama
Y
Y
Mitsuhashi
S
S
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001790:Blood Physiological Phenomena; D004355:Drug Stability; D004926:Escherichia coli / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D007769:Lactams; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000494:pharmacology; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D007769:Lactams; D047090:beta-Lactams; C082897:sulopenem; D001618:beta-Lactamases