Comparison of two schedules of cefoperazone plus aztreonam in the treatment of neutropenic patients with fever.

Cancer patients were randomized to receive an every 4 hour or every 8 hour schedule of cefoperazone plus aztreonam during 617 febrile episodes. The overall response rate for the 478 evaluable episodes was 76% and there was no difference in response rate between the two schedules. The response rate was 79% for cases of pneumonia and 63% for cases of bacteremia. Only 50% of the microbiologically documented infections caused by gram-positive organisms responded whereas 95% of gram-negative infections, including all of those caused by Pseudomonas aeruginosa, responded. Response rates were lower among patients whose neutrophil counts decreased during therapy than among those whose neutrophil counts increased (64% vs. 85%, p = 0.008). Side-effects that were possibly or probably related to antibiotic therapy were observed during 11% of the episodes. The most common side-effects were diarrhea and rashes including one case of Stevens-Johnson syndrome. Three patients developed a coagulopathy during therapy. Cefoperazone plus aztreonam proved to be an effective combination for treatment of gram-negative infections and fever of unknown origin in cancer patients and an every 8-hour schedule of administration was as effective as an every 4-hour schedule. Approximately half of the patients with gram-positive infections required additional antibiotics for successful therapy.