Quantitative relationship between sensitivity to beta-lactam antibiotics and beta-lactamase production in gram-negative bacteria--II. Non-steady-state treatment and progress curves.
A non-steady-state model is discussed for the study of the interplay between beta-lactamase activity and outer membrane permeability with slowly hydrolysed beta-lactams. The analysis shows: (1) that the simple, steady-state model presented in the accompanying paper remains valid as long as kcat (i.e. k3 with chromosome-encoded class C beta-lactamases) is larger than 10(-3)/sec (generation time = 20 min or more); (2) that among the beta-lactam antibiotics studied here, the complete, non-steady-state model needs only be used in the case of aztreonam; (3) that the term "trapping" should be replaced by "formation of a covalent acyl-enzyme" and that such a phenomenon only contributes significantly to the resistance when penetration and hydrolysis are very slow and the periplasmic beta-lactamase concentration is very high. Aztreonam seems to be the only compound which fulfils the first two conditions.
Frère
J M
JM
Laboratoire d'Enzymologie, Université de Liège, Belgium.
Joris
B
B
Crine
M
M
Martin
H H
HH
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism; D002442:Ceftazidime / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000201:enzymology; D006602:Hexosyltransferases; D015378:Imipenem / Q000494:pharmacology; D008433:Mathematics; D008826:Microbial Sensitivity Tests; D009070:Moxalactam / Q000494:pharmacology; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D001618:beta-Lactamases / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D015378:Imipenem; D002442:Ceftazidime; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases; D009070:Moxalactam