An explicit model for bacterial resistance: application to beta-lactam antibiotics.
The effectiveness of beta-lactam antibiotics against Gram-negative bacteria that contain beta-lactamases is considered in terms of three factors. These are a rate constant for reaction of the beta-lactam antibiotic with a transpeptidase, the kinetic parameters for hydrolysis of the antibiotic by the beta-lactamase, and the permeability of the outer membrane. The concept of a dimensionless permeability number (Pn) is developed. When the permeability number is much less than one then permeability is important, and the MIC may be raised by a factor of up to 1/Pn. When the antibiotic is sufficiently reactive its effectiveness is given by the 'reactivity-permeability' product.
Waley
S G
SG
Sir William Dunn School of Pathology, University of Oxford, UK.
D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D004352:Drug Resistance, Microbial / Q000502:physiology; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D010539:Permeability; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D001618:beta-Lactamases