[In vitro antibacterial activity of a new parenteral penem, sulopenem].
Eighty percent minimum inhibitory concentrations (MIC80) of sulopenem against clinically isolated 12 to 80 strains of each of different bacteria were as follows: methicillin-susceptible Staphylococcus aureus (MSSA): 0.20 micrograms/ml, methicillin-resistant S. aureus (MRSA): 50 micrograms/ml, coagulase-negative staphylococci: 3.13 micrograms/ml, Streptococcus pyogenes: < or = 0.013 microgram/ml, Streptococcus pneumoniae: < or = 0.013 microgram/ml, beta-streptococci: 0.05 microgram/ml, Enterococcus faecalis: 12.5 micrograms/ml, Enterococcus faecium: > 100 micrograms/ml, Escherichia coli CS2(R+): 0.10 microgram/ml, Klebsiella pneumoniae: 0.05 microgram/ml, Proteus mirabilis: 0.10 microgram/ml, Proteus vulgaris: 0.20 microgram/ml, Morganella morganii: 0.39 micrograms/ml, Providencia rettgeri: 3.13 micrograms/ml, Citrobacter freundii: 0.20 microgram/ml, Enterobacter cloacae: 0.39 microgram/ml, Serratia marcescens: 1.56 micrograms/ml, Pseudomonas aeruginosa: 50 micrograms/ml, Pseudomonas cepacia: 3.13 micrograms/ml, Xanthomonas maltophilia: > 100 micrograms/ml, Acinetobacter calcoaceticus: 1.56 micrograms/ml, ampicillin-resistant Haemophilus influenzae: 0.39 microgram/ml and Bacteroides fragil is: 0.20 microgram/ml, respectively. Sulopenem possesses a stronger activity than flomoxef or cefuzonam against Gram-positive bacteria, the strongest activity among the antibiotics tested against Gram-negative bacteria except P. aeruginosa. Sulopenem has stronger affinities than imipenem to all fractions of PBPs of S. aureus, E. coli, P. vulgaris, S. marcescens, even of P. aeruginosa. Affinities of sulopenem to PBPs-1 and -3 of S. aureus, PBP-2 of E. coli were much stronger than those of imipenem (IPM). Sulopenem generally has small Ki values to all types of beta-lactamases and also has stronger permanent inactivation effect to Ia and IIb types of beta-lactamases than IPM. No synergistic bactericidal activity of sulopenem was apparent with serum complement. However, synergism of sulopenem with macrophages was prominent in bactericidal activity. The cells of E. coli were well phagocytosed and rapidly digested by cultured macrophages in the presence of a higher than 1/8 MIC of sulopenem. Moreover, sulopenem was more stable than imipenem against swine and human dehydropeptidase-Is. Sulopenem is one of the antibiotics that do not induce the appearance of subclones resistant to the drug.
Yoshida
T
T
Department of Bacteriology, School of Medicine, Juntendo University, Tokyo, Japan.
Tateda
E
E
Hiramatsu
K
K
Yokota
T
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004927:Escherichia coli Infections / Q000188:drug therapy; D006602:Hexosyltransferases; D015378:Imipenem / Q000494:pharmacology; D007769:Lactams; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D018440:beta-Lactam Resistance; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D007769:Lactams; D046915:Penicillin-Binding Proteins; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; C082897:sulopenem; D015378:Imipenem; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase