Cefpirome (HR 810): lack of selection of beta-lactamase overproducing variants.
With respect to the selection of beta-lactam-resistant variants marked discrepancies between the recently developed cephalosporin HR 810 and other recently developed cephalosporins could be observed: beta-lactam resistant subpopulations did not emerge during a 16-hour culture in the presence of the 20-fold minimal inhibitory concentration in a clinical Enterobacter cloacae isolate (2240/81) in contrast to cefoperazone, cefotaxime, ceftriaxone and ceftazidime. Breakdown of the antibacterial agents during the 16-hour period as evaluated by monitoring their levels in the medium was not responsible for selection of beta-lactam-resistant subpopulations. The study of affinity of various cephalosporins to the chromosomally mediated beta-lactamase of E. cloacae strain 2240/81 revealed low affinity of HR 810 to the enzyme (Ki amounted 4.4 X 10(-3)M). It is suggested that the low affinity of this new agent to the E. cloacae enzyme plays a major role in the lack of selection of resistant subpopulations.
D002511:Cephalosporins / Q000378:metabolism* / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004754:Enterobacter / Q000145:classification / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D004755:Enterobacteriaceae / Q000201:enzymology*; D007700:Kinetics; D001618:beta-Lactamases / Q000096:biosynthesis / Q000378:metabolism*; D000097572:Cefpirome
D002511:Cephalosporins; D001618:beta-Lactamases; D000097572:Cefpirome