Anomalous effect of serum on the antimicrobial activity of cefoperazone

This study investigated the effect of added serum on cefoperazone activity in vitro. Due to protein-binding, an 8-fold difference would be expected between minimum inhibitory concentrations in broth and in broth plus 90% serum. Using supplemented Mueller-Hinton broth (sMH) and sMH plus 90% heat-inactivated human serum there were differences of 3.36 +/- 0.92 for Staphylococcus aureus strain ATCC1 25923, 1.39 +/- 0.47 for Escherichia coli strain ATCC 25922 and 1.43 +/- 0.39 for Pseudomonas aeruginosa strain ATCC 27853. Serum-related modal increases in minimum inhibitory concentrations of cefoperazone for clinical isolates were 4-fold versus Staphylococcus aureus (5 strains), Klebsiella species (5 strains) and Pseudomonas aeruginosa (8 strains), and 2-fold versus Escherichia coli (4 strains). On the addition of serum to 2 strains of Serratia marcescens, divergent effects were seen. Minimum lethal concentrations of cefoperazone were generally identical to, or a low multiple of, corresponding minimum inhibitory concentrations. Variables other than protein binding may account for the anomalous activity of antibiotics against organisms in serum. These factors favour the activity of cefoperazone against several clinically important species.