title: Benzylpenicillin plus an aminoglycoside versus meropenem in neutropenic lymphoma and leukaemia patients with a suspected bacterial infection: a randomized, controlled trial.
abstract: OBJECTIVE
  In Norway, initial treatment of febrile neutropenia (FN) has traditionally been benzylpenicillin plus an aminoglycoside. Internationally, FN is often treated with a broad-spectrum β-lactam antibiotic. We aimed to compare these two regimens in a prospective, randomized, trial in patients with lymphoma or leukaemia with an expected period of neutropenia ≥7 days, and a suspected bacterial infection.
  
  
  METHODS
  Adult neutropenic patients with lymphoma or leukaemia, and a suspected bacterial infection, were randomized for treatment with benzylpenicillin plus an aminoglycoside or meropenem. The primary endpoint was clinical success, defined as no modification of antibiotics and clinical stability 72 h after randomization.
  
  
  RESULTS
  Among 322 randomized patients, 297 proved evaluable for analyses. Fifty-nine per cent (95% CI 51%-66%), (87/148) of the patients given benzylpenicillin plus an aminoglycoside were clinically stable, and had no antibiotic modifications 72 h after randomization, compared with 82% (95% CI 75%-87%), (122/149) of the patients given meropenem (p <0.001). When the antibiotic therapy was stopped, 24% (95% CI 18%-32%), (36/148) of the patients given benzylpenicillin plus an aminoglycoside, compared with 52% (95% CI 44%-60%), (78/149) of the patients given meropenem, had no modifications of their regimens (p <0.001). In the benzylpenicillin plus an aminoglycoside arm, the all-cause fatality within 30 days of randomization was 3.4% (95% CI 1.2%-7.9%), (5/148) of the patients, compared with 0% (95% CI 0.0%-3.0%), (0/149) of the patients in the meropenem arm (p 0.03).
  
  
  CONCLUSIONS
  Clinical success was more common in FN patients randomized to meropenem compared with the patients randomized to benzylpenicillin plus an aminoglycoside. The all-cause fatality was higher among the patients given benzylpenicillin plus an aminoglycoside.
authors: Department of Oncology, Division of Cancer Medicine, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Electronic address: dag.torfoss@ous-hf.no.
authors: D
authors: D
authors: Torfoss
authors: Department of Oncology, Division of Cancer Medicine, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors: T
authors: T
authors: Fladhagen
authors: Department of Oncology, Division of Cancer Medicine, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors: H
authors: H
authors: Holte
authors: Department of Haematology, Division of Cancer Medicine, The National Hospital, Oslo University Hospital, Oslo, Norway.
authors: L
authors: L
authors: Brinch
authors: Department of Haematology, Division of Cancer Medicine, The National Hospital, Oslo University Hospital, Oslo, Norway.
authors: F H
authors: FH
authors: Schjesvold
authors: Department of Haematology, Division of Cancer Medicine, The National Hospital, Oslo University Hospital, Oslo, Norway.
authors: Y
authors: Y
authors: Fløisand
authors: Department of Haematology, Division of Cancer Medicine, Ullevål University Hospital, Oslo University Hospital, Oslo, Norway.
authors: E
authors: E
authors: Nyquist
authors: Medical Clinic, Vestre Viken Hospital, Drammen, Norway.
authors: J
authors: J
authors: Dalgaard
authors: Department of Haematology and Oncology, Stavanger University Hospital, Stavanger, Norway.
authors: P
authors: P
authors: Meyer
authors: Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors: A K
authors: AK
authors: Lehmann
authors: Department of Haematology, St Olav University Hospital, Trondheim, Norway.
authors: J
authors: J
authors: Hammerstrøm
authors: Department of Haematology, University Hospital of North Norway, Tromsø, Norway.
authors: T
authors: T
authors: Skjelbakken
authors: National Institute of Public Health, Oslo, Norway.
authors: E A
authors: EA
authors: Høiby
authors: Oslo Centre of Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway.
authors: L
authors: L
authors: Sandvik
authors: Department of Oncology, Division of Cancer Medicine, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors: S
authors: S
authors: Kvaløy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000617:Aminoglycosides / Q000008:administration & dosage*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001424:Bacterial Infections / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007938:Leukemia / Q000150:complications*; D008223:Lymphoma / Q000150:complications*; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D009026:Mortality; D009503:Neutropenia / Q000150:complications; D009664:Norway; D010400:Penicillin G / Q000008:administration & dosage*; D011446:Prospective Studies; D013845:Thienamycins / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem; D010400:Penicillin G
keywords: Aminoglycosides; Benzylpenicillin; Febrile neutropenia; Meropenem; Randomized controlled trial