In vitro activity, beta-lactamase stability and PBP affinity of RU 51,746-2, the active metabolite of the new orally absorbed cephalosporin ester, RU 51807.
The activity of RU 51,746-2 was determined against strains of Escherichia coli producing different types of beta-lactamases or showing alterations of permeability. The production of TEM 1, OXA 2, CARB 3 and PSE 1 beta-lactamases had no influence on susceptibility to the antibiotic, whereas the synthesis of TEM 2, SHV 1 and OXA 1 beta-lactamases increased minimum inhibitory concentrations (MIC) by 2-4 times. Highly resistant to the antibiotic was a strain producing CEP 1 beta-lactamase. E. coli mutans deficient in Omp F but not in Omp C had a decreased susceptibility to RU 51,746-2. RU 51,746-2 showed a good affinity for high molecular weight penicillin binding proteins (PBPs) of E. coli. PBP 3 was found to be the target for growth inhibition, whereas the additional saturation of PBP 1 and 2 was required for obtaining the best bactericidal activity.
Boaretti
M
M
Istituto di Microbiologia, Università degli Studi di Verona, Italy.
Lleó
M M
MM
Canepari
P
P
D002352:Carrier Proteins / Q000378:metabolism; D015296:Ceftizoxime / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D056913:Mediator Complex Subunit 1; D008826:Microbial Sensitivity Tests; D014157:Transcription Factors; D001618:beta-Lactamases / Q000096:biosynthesis / Q000494:pharmacology*; D000097623:Cefpodoxime
D002352:Carrier Proteins; D015296:Ceftizoxime; D002511:Cephalosporins; D056913:Mediator Complex Subunit 1; D014157:Transcription Factors; D001618:beta-Lactamases; D000097623:Cefpodoxime