Interactions of meropenem, with beta-lactamases, including enzymes with extended-spectrum activity against third-generation cephalosporins.
The interactions of a meropenem were studied with a set of beta-lactamases including the new TEM- and SHV-related plasmid-mediated enzymes that have extended-spectrum activity against third-generation cephalosporins ('cefotaximases' and 'ceftazidimases'). Meropenem and imipenem were highly resistant to the hydrolytic activity of all the TEM and SHV related beta-lactamases, and to the OXA enzymes, as were the cephamycins: cefoxitin and cefotetan. The two carbapenems were also highly stable to Class C beta-lactamases (chromosomal cephalosporinases) whereas third-generation cephalosporins and cephamycins were slowly hydrolyzed. Both carbapenems demonstrated quite similar affinities for all the enzymes studied. In some instances, and particularly with Class A (TEM- and SHV-derived) enzymes, meropenem inactivated the beta-lactamase activity. Imipenem appeared less reactive in this respect.
Labia
R
R
Muséum National d'Histoire Naturelle, CNRS, Paris, France.
Morand
A
A
Tiwari
K
K
Sirot
D
D
Chanal
C
C
D000215:Acylation; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology; D015780:Carbapenems / Q000494:pharmacology*; D002511:Cephalosporins / Q000378:metabolism*; D007700:Kinetics; D000077731:Meropenem; D013845:Thienamycins / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000096:biosynthesis
D015780:Carbapenems; D002511:Cephalosporins; D013845:Thienamycins; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases; D000077731:Meropenem