Enhancing effect of serum ultrafiltrate on the activity of cephalosporins against gram-negative bacilli.

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Leggett JE, Craig WA

Enhancing effect of serum ultrafiltrate on the activity of cephalosporins against gram-negative bacilli.

Antimicrob Agents Chemother. 1989 Jan;33(1):35-40.

PubMed ID

2496656 [ View in PubMed

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Abstract

A few studies have suggested that the inhibitory effect of serum on activity of broad-spectrum cephalosporins is less than that predicted by the degree of protein binding. Microdilution MICs of ceftriaxone, cefoperazone, moxalactam, and ceftizoxime were therefore determined against ATCC and clinical strains of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus in Mueller-Hinton broth containing either human albumin (as 0, 2.5, or 5% solution) or heat-inactivated human serum (as 0, 25, 50, or 95% solution). Arithmetic linear dilutions were used to improve accuracy. For standard bacterial strains, MICs in the presence of 5% albumin were higher than in broth alone by multiples of 10.9 to 21 for ceftriaxone, 5.5 to 16.4 for cefoperazone, 1.9 to 3.7 for moxalactam, and 1.1 to 1.4 for ceftizoxime, as expected by their protein binding. MICs in the presence of 95% serum were similar to those in 5% albumin for all four drugs against S. aureus and P. aeruginosa but were 2.2- to 4.8-fold lower (P less than 0.001) against E. coli and K. pneumoniae. Similar findings were observed at lower protein concentrations and with clinical isolates, except that for some strains of P. aeruginosa MICs were lower in serum than in albumin. Individual sera from five subjects gave comparable results. The addition of serum ultrafiltrate to albumin-containing solutions reduced MICs of ceftriaxone and cefoperazone 1.6- to 7.4-fold against E. coli and K. pneumoniae (P less than 0.01) but did not alter the MICs for S. aureus. Serum may contain an ultrafiltrable component(s) that enhances the activity of third-generation cephalosporins against many gram-negative bacilli.

DrugBank Data that Cites this Article

Drug Carriers

Drug	Carrier	Kind	Organism	Pharmacological Action	Actions
Cefoperazone	Serum albumin	Protein	Humans	No	Other/unknown	Details