Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragilis.

Article Details

Citation

Yotsuji A, Mitsuyama J, Hori R, Yasuda T, Saikawa I, Inoue M, Mitsuhashi S

Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragilis.

Antimicrob Agents Chemother. 1988 Dec;32(12):1848-53.

PubMed ID
3266730 [ View in PubMed
]
Abstract

The susceptibilities of 52 clinical isolates of Bacteroides fragilis to five monoanionic cephalosporins were examined. Cefoperazone showed the highest antibacterial activity, followed by ceftezole, cefazolin, cefamandole, and cephalothin. There were two groups of resistant strains: one group (ca. 15%), of which B. fragilis G-232 was a typical sample, was resistant to ceftezole (MIC, 100 micrograms/ml), cefazolin (MIC, 100 micrograms/ml), and cephalothin (MIC, 200 micrograms/ml) but not cefoperazone (MIC, 6.25 micrograms/ml) or cefamandole (MIC, 25 micrograms/ml). On the basis of studies of stability to beta-lactamase, outer membrane permeation, and affinity for penicillin-binding proteins (PBPs), we conclude that decreased affinity for PBP 3 may play an important role in the resistance to ceftezole, cefazolin, and cephalothin in B. fragilis G-232. Another group (also ca. 15%), of which B. fragilis G-242 was a representative, was resistant to all five cephalosporins (MIC, 100 to 400 micrograms/ml) and produced a high amount of beta-lactamase. Similar broad-spectrum resistance was seen in a mutant of strain G-232 that had a greater-than-30-fold increase in beta-lactamase production.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
CefacetrilePenicillin-binding protein 1AProteinEscherichia coli (strain K12)
Yes
Inhibitor
Details
CefacetrilePenicillin-binding protein 1BProteinEscherichia coli (strain K12)
Yes
Inhibitor
Details
CefamandolePenicillin-binding protein 2ProteinBacteroides fragilis
Yes
Inhibitor
Details
CefazolinPenicillin-binding protein 1AProteinEscherichia coli (strain K12)
Yes
Inhibitor
Details
CefazolinPenicillin-binding protein 1BProteinEscherichia coli (strain K12)
Yes
Inhibitor
Details
CefazolinPenicillin-binding protein 1CProteinEscherichia coli (strain K12)
Yes
Inhibitor
Details
CefazolinPenicillin-binding protein 2ProteinEscherichia coli (strain K12)
Yes
Inhibitor
Details
CefazolinPeptidoglycan synthase FtsIProteinEscherichia coli (strain K12)
Yes
Inhibitor
Details
CeforanidePenicillin-binding protein 2ProteinBacteroides fragilis
Yes
Inhibitor
Details