Effect of dose and schedule on cefoperazone pharmacodynamics in an in vitro model of infection in a neutropenic host.

Previous studies have shown that cefoperazone given in frequent, large doses is effective in the treatment of infection in patients with cancer. The pharmacodynamics of 2- and 4-g doses of cefoperazone administered either as a single dose or at 12-hour intervals were studied in an in vitro model that simulates infection in a neutropenic patient. One strain each of Pseudomonas aeruginosa (minimal inhibitory concentration [MIC] = 2 micrograms/ml), Staphylococcus aureus (MIC = 1 microgram/ml), Escherichia coli (MIC = 0.06 micrograms/ml), and Klebsiella pneumoniae (MIC = 0.25 micrograms/ml) was studied. The initial dose reduced the inoculum by approximately 3 logs for the Pseudomonas and the staphylococci and 3 to 5 logs for the other organisms. No significant differences in killing were found between the 2- and 4-g doses. Regrowth of Pseudomonas and staphylococci occurred with the single dose but not with the every-12-hour regimen. These data support the clinical use of cefoperazone in doses every 12 hours.