Effect of serum on the in vitro activities of 11 broad-spectrum antibiotics

We evaluated the effect of serum on the in vitro activities of 11 antimicrobial agents against gram-negative isolates obtained from 100 patients with nosocomial bacteremia. The test organisms included 25 strains of Pseudomonas aeruginosa and 75 strains of the family Enterobacteriaceae. MICs were determined by broth microdilution with Mueller-Hinton broth alone or supplemented with 25 or 50% pooled, heat-inactivated human serum (25S or 50S, respectively). Among the antibiotics evaluated, the protein binding ranged from 9 to 95%. The antibiotics tested and their MICs for 90% of the strains tested in 50S included ciprofloxacin (0.12 μg/ml), ceftazidime (1 μg/ml), imipenem (1 μg/ml), aztreonam (4 μg/ml), cefpirome (4 μg/ml), cefotaxime (16 μg/ml), cefoperazone (16 μg/ml), desacetylcefotaxime plus cefotaxime (32 μg/ml), ceftriaxone (>32 μg/ml), ticarcillin (128 μg/ml), and desacetylcefotaxime (>128 μg/ml). MICs for 90% of the strains tested were calculated with 95% confidence intervals to show the precision of the MICs for these strains. With the exceptions of ceftriaxone (>95% protein bound) and cefoperazone (90% protein bound), serum had no significant effect on the in vitro activities of various agents. A fourfold-or-greater increase in the MIC of ceftriaxone was observed in 45 of 100 isolates with 50S and in 30 of 100 isolates with 25S. With cefoperazone, 17 of 100 isolates demonstrated more than 2 twofold dilution increases in 50S. Testing of antibiotics which were less protein bound illustrated minor effects primarily with members of the Enterobacteriaceae. The presence of serum did not adversely affect the in vitro activities of broad-spectrum agents against these nosocomial isolates.