Mechanism of action of BAY v 3522, a new cephalosporin with unusually good activity against enterococci.
The in vitro activity of BAY v 3522, a new cephalosporin with unusually good activity against enterococci, was tested on 100 clinical isolates of Enterococcus faecalis. The MIC for 86.3% of the strains was 4 micrograms/ml, whereas the MIC for 13.7% ranged from 8 to 16 micrograms/ml. No differences were found between MICs determined with low- or high-density inocula. The bactericidal activity of BAY v 3522 was tested on eight clinical strains; most strains showed a ca. 3-log decrease of the original inoculum at two to eight times the MIC. The interaction of BAY v 3522 and of other beta-lactams with penicillin-binding proteins (PBPs) was studied with a laboratory strain, E. hirae ATCC 9790, producing a discernible amount of PBP 5, a protein belonging to the family of low-affinity PBPs, responsible for the low susceptibility of enterococci to beta-lactams. PBPs 3 and 5 of ATCC 9790 showed the highest affinity for the new cephalosporin. Bay V 3522 at the MIC (8 micrograms/ml) saturated these two PBPs without any significant binding to the other PBPs. This result may explain the good antienterococcal activity of BAY v 3522.
Amalfitano
G
G
Institute of Microbiology, University of Verona, Italy.
Grossato
A
A
Fontana
R
R
D000667:Ampicillin / Q000494:pharmacology; D052160:Benzothiazoles; D002511:Cephalosporins / Q000494:pharmacology*; D016983:Enterococcus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests
D052160:Benzothiazoles; D002511:Cephalosporins; C064738:Bay v 3522; D000667:Ampicillin