MEN 10700, a new penem antibiotic: in-vitro activity and its correlation with beta-lactamase stability, PBP affinity and diffusion through the bacterial cell wall.
The in-vitro activity of MEN 10700, a novel penem, was compared with that of imipenem, ritipenem, ampicillin/sulbactam, cefotaxime, ciprofloxacin and amikacin against 1088 strains taken from 21 genera, including Gram-negative, Gram-positive and anaerobic bacteria. MIC data showed that MEN 10700 was very active against staphylococci and streptococci (MIC90 < or = 0.5 mg/L) and against most members of the Enterobacteriaceae (MIC90 < or = 2 mg/L), with reduced activity only against Providencia stuartii (MIC90 = 8 mg/L). MEN 10700 was also active against anaerobic species such as Clostridium perfringens and Bacteroides fragilis as well as Moraxella catarrhalis. It was moderately active against Enterococcus faecalis and inactive against Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Aeromonas spp. and Acinetobacter spp. Its antibacterial spectrum was thus slightly narrower than that of imipenem, but compared favourably with those of a third-generation cephalosporin and ritipenem. MEN 10700 was highly stable to a number of beta-lactamases and was a poor inducer of class I enzymes. It bound penicillin-binding protein 2 with the highest affinity and easily permeated the outer membrane of Escherichia coli.
Fontana
R
R
Istituto di Microbiologia, Università di Verona, Italy.
Altamura
M
M
Arcamone
F
F
Mazzariol
A
A
Morandotti
G
G
Sperning
R
R
Cornaglia
G
G
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification / Q000378:metabolism; D001421:Bacteria, Anaerobic / Q000187:drug effects / Q000201:enzymology / Q000302:isolation & purification / Q000378:metabolism; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D015169:Colony Count, Microbial; D004058:Diffusion; D004355:Drug Stability; D004790:Enzyme Induction; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000201:enzymology / Q000302:isolation & purification / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000201:enzymology / Q000302:isolation & purification / Q000378:metabolism; D006602:Hexosyltransferases; D006801:Humans; D007700:Kinetics; D007769:Lactams; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism*; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000378:metabolism*; D010458:Peptidyl Transferases; D001618:beta-Lactamases / Q000096:biosynthesis / Q000378:metabolism*; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D007769:Lactams; C106870:Men 10700; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D047090:beta-Lactams; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases