Evolution of enzymatic mechanisms of resistance among beta-lactam antibiotics.
Resistance to third-generation cephalosporins occurs as a result of either the production of high concentrations of chromosomal cephalosporinase or, increasingly, the presence of broad-spectrum plasmid-mediated beta-lactamases. Both cases represent the response of bacteria in the hospital setting to the selection pressure brought to bear by the use of these antibiotics. Continued evolution of the plasmid-mediated enzymes is occurring as new antibiotics are introduced, probably reflecting the process that began when the first beta-lactamase apparently evolved from the penicillin-binding proteins. beta-Lactamase inhibitors offer one approach to dealing with the evolution of resistance to previously beta-lactamase-stable antibiotics.
Gutmann
L
L
Medical Microbiology Laboratory, Broussais Hospital, Paris, France.
Kitzis
M D
MD
Acar
J F
JF
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D002510:Cephalosporinase / Q000235:genetics; D002511:Cephalosporins / Q000378:metabolism; D002876:Chromosomes, Bacterial / Q000201:enzymology; D004352:Drug Resistance, Microbial; D004755:Enterobacteriaceae / Q000201:enzymology*; D008969:Molecular Sequence Data; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D001618:beta-Lactamases / Q000235:genetics*
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D002510:Cephalosporinase; D001618:beta-Lactamases