title: A prospective, randomized study comparing cefepime and imipenem-cilastatin in the empirical treatment of febrile neutropenia in patients treated for haematological malignancies.
abstract: A prospective, open label, randomized, multicentre study was conducted, comparing the efficacy and safety of cefepime with that of imipenem-cilastatin for the management of febrile neutropenia in patients with haematological malignancies. Furthermore, the safety of early discontinuation of antibiotic therapy in patients with fever of undetermined origin (FUO) was assessed. A total of 180 patients with 207 febrile episodes were randomized at start of fever (105 episodes for cefepime and 102 episodes for imipenem). The 2 groups were comparable in terms of age, gender, underlying malignancy, prior transplantation, and presence of central venous catheters. All patients were neutropenic at inclusion with median absolute neutrophil count (ANC) 0.1 x 10(9)/l(range 0-1 x 10(9)/l), and ANC < or = 0.1 x 10(9)/l in 77% of included patients. The mean duration of neutropenia, with ANC < 0.5 x 10(9)/l was 6.2 d. Febrile episodes were classified as microbiologically documented infection (47%), FUO (43%), or clinically documented infection (10%). At final evaluation 1-2 weeks after completion of antibiotic therapy, monotherapy success rates were 40% and 51% in the cefepime and imipenem-cilastatin groups respectively (p = 0.33). The 4-week overall mortality rate was 5%. Three (2%) of the cefepime treated patients and 4 (3%) of the imipenem-cilastatin treated patients died as a result of infection. Adverse events directly related to antibiotic treatment were uncommon and did not differ between groups. Early discontinuation of antibiotic therapy in 31 patients with FUO 48 h after defervescence was not associated with an increased rate of fever relapse or mortality compared with a subgroup of 29 patients where therapy was continued.
authors.affiliation: Department of Medicine, Division of Haematology, Karolinska Hospital and Institute, Stockholm, Sweden. honar.cherif@kus.se
authors.forename: Honar
authors.initials: H
authors.lastname: Cherif
authors.forename: Magnus
authors.initials: M
authors.lastname: Björkholm
authors.forename: Per
authors.initials: P
authors.lastname: Engervall
authors.forename: Peter
authors.initials: P
authors.lastname: Johansson
authors.forename: Per
authors.initials: P
authors.lastname: Ljungman
authors.forename: Robert
authors.initials: R
authors.lastname: Hast
authors.forename: Mats
authors.initials: M
authors.lastname: Kalin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage*; D015377:Cilastatin / Q000008:administration & dosage*; D000077728:Cilastatin, Imipenem Drug Combination; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005334:Fever / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D005500:Follow-Up Studies; D019337:Hematologic Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D011336:Probability; D011446:Prospective Studies; D018570:Risk Assessment; D016037:Single-Blind Method; D016019:Survival Analysis; D013548:Sweden; D016896:Treatment Outcome
chemical_list: D002511:Cephalosporins; D004338:Drug Combinations; D015377:Cilastatin; D015378:Imipenem; D000077723:Cefepime; D000077728:Cilastatin, Imipenem Drug Combination