HOW SHOULD IMIPENEM-CILASTATIN BE USED IN THE TREATMENT OF FEVER AND INFECTION IN NEUTROPENIC CANCER-PATIENTS

BACKGROUND. Imipenem-cilastatin (referred to hereafter as imipenem) is administered at different doses as monotherapy or with other agents. Limited comparisons of the alternatives exist. The authors compared th e efficacy and safety of several imipenem-containing regimens (ICRs) t o determine the appropriate dose and the need for combination therapy. METHODS. Between 1985 and 1994, febrile neutropenic patients were giv en ICRs according to the same methodology on prospective trials at a r eferral cancer center. The ICRs were high dose imipenem (HIP), high do se imipenem and amikacin (HIPA), high dose imipenem and vancomycin (HI PV), and low dose imipenem and vancomycin (LIPV). RESULTS. The overall response rates were comparable (70-77%). There was a univariate trend toward better response among patients with pneumonia and documented i nfections with unidentified organisms who received HIPV versus LIPV (P = 0.06), as well as a significantly better response among patients wi th gram positive infections who received HIPV versus HIP (P = 0.02) an d HIPA (P = 0.002). HIPV was a more effective treatment for documented infections with identified organisms (P = 0.05) and bloodstream infec tions (P = 0.04) than HIP; there was a univariate trend toward better response among patients infected with gram negative organisms who rece ived HIPA versus HIP (P = 0.12). Multivariate adjustment for baseline and prognostic factors did not reveal a relative advantage for any reg imen. No differences in overall toxicities were observed between HIPV and LIPV. CONCLUSIONS. Imipenem monotherapy is adequate treatment for most febrile neutropenic cancer patients. Low dose imipenem could be e ffective and safe in uncomplicated cases without pneumonia. Further st udies are needed to establish the usefulness of low dose imipenem in t his context. (C) 1998 American Cancer Society.