Interaction of ceftriaxone with penicillin-binding proteins of Escherichia coli in the presence of human serum albumin.
The binding of ceftriaxone, a cephalosporin that exhibits high serum protein binding and prolonged serum half-life, to penicillin-binding proteins (PBPs) of Escherichia coli K12 in the presence of human serum albumin was compared with plasma concentrations of cefotaxime, a cephalosporin with low serum protein binding and a short serum half-life. Ceftriaxone concentrations equivalent to those maintained in plasma for 8 h after an intravenous infusion of 1 g saturated PBPs 2 and 3. Cefotaxime saturated both PBPs at concentrations equivalent to those maintained for 2 h, and PBP 3 only at concentrations maintained for 2-8 h. These results indicate that high serum protein binding does not impair the ability of ceftriaxone to inhibit essential PBPs, and explain the high in-vivo efficacy of the drug.
Istituto di Microbiologia, Università di Verona, Italy.
R
R
Fontana
M
M
Aldegheri
M
M
Ligozzi
G
G
Lo Cascio
G
G
Cornaglia
D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D002443:Ceftriaxone / Q000378:metabolism* / Q000494:pharmacology; D002511:Cephalosporins / Q000378:metabolism* / Q000494:pharmacology; D004926:Escherichia coli / Q000378:metabolism*; D006207:Half-Life; D006602:Hexosyltransferases; D006801:Humans; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism*; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D012709:Serum Albumin / Q000378:metabolism*
D001426:Bacterial Proteins; D002352:Carrier Proteins; D002511:Cephalosporins; D046915:Penicillin-Binding Proteins; D012709:Serum Albumin; D002443:Ceftriaxone; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase