In vitro studies with Bay V 3522, a new oral cephalosporin.
The in vitro activities of Bay v 3522, cefaclor, cephalexin, cefuroxime, cefixime, amoxicillin/clavulanate (2:1) and reference penicillins were compared against 314 clinical isolates of Gram-positive and Gram-negative bacteria and nine strains of Escherichia coli that differed in their outer membrane proteins in agar dilution tests with an inoculum of 10(4) cfu/spot. The beta-lactamase stabilities of the cephalosporins were also evaluated by spectrophotometric assay using 21 different beta-lactamases. Bay v 3522 was the most potent cephalosporin overall against Gram-positive pathogens, but slightly less active than amoxicillin/clavulanate. In addition to being highly active against streptococci (MIC90 = 0.25 micrograms/ml) and methicillin-susceptible staphylococci (MIC90 = 1.0 micrograms/ml), Bay v 3522 was markedly more active than the other cephalosporins against Enterococcus faecalis (MIC90 = 4 micrograms/ml). Bay v 3522 was less potent against Gram-negative pathogens, especially nosocomial isolates of Escherichia coli and Klebsiella pneumoniae (MIC90 greater than 64 micrograms/ml), but was active against Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and beta-lactamase-negative Neisseria gonorrhoeae (MIC90 = 1.0 micrograms/ml0. Hydrolysis of Bay v 3522 by most beta-lactamases examined was significantly less than that observed for cephalothin and cefaclor; similar to that observed with cephalexin; and less than that observed with cefixime and cefuroxime. None of the beta-lactamases examined hydrolysed Bay v 3522 at a rate greater than 20 nmol/min/mg. The in vitro potency of Bay v 3522 against Gram-positive and fastidious Gram-negative pathogens and its resistance to hydrolysis by beta-lactamases produced by them support further investigation of this cephalosporin as a new oral therapeutic agent.
Creighton University School of Medicine, Omaha, NE 68178.
K S
KS
Thomson
C C
CC
Sanders
W E
WE
Sanders
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D052160:Benzothiazoles; D002511:Cephalosporins / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006868:Hydrolysis; D008826:Microbial Sensitivity Tests; D010406:Penicillins / Q000494:pharmacology; D001618:beta-Lactamases / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D052160:Benzothiazoles; D002511:Cephalosporins; D010406:Penicillins; C064738:Bay v 3522; D001618:beta-Lactamases