title: Tobramycin once versus three times daily, given with penicillin G, to febrile neutropenic cancer patients in Norway: a prospective, randomized, multicentre trial.
abstract: OBJECTIVE
  Penicillin G with an aminoglycoside is the standard initial empirical treatment in febrile neutropenia in Norway. It has been argued that giving the aminoglycoside once daily to neutropenic patients with Gram-negative bacteraemia may be hazardous when penicillin G is the beta-lactam antibiotic. We questioned this argument and hypothesized that tobramycin once daily was as efficacious as three times daily.
  
  
  METHODS
  We conducted a randomized prospective multicentre study, comparing the efficacy of tobramycin 6 mg/kg once (arm A) versus three times (arm B) daily, plus penicillin G 5 million IU x 4, in febrile neutropenic cancer patients.
  
  
  METHODS
  modification of the antibiotic regimen.
  
  
  RESULTS
  One hundred and seventy-four patients were evaluable for intention-to-treat analyses. One hundred and fifty-five patients had lymphoma or leukaemia as the underlying cancer diagnosis. In arm A, 35 of 88 patients and in arm B, 34 of 86 patients, that is 40% in both arms had no modification of the antibiotic regimen. No patients died while participating in the study. Upon modification of the antibiotic regimen, all patients were successfully treated. The increase in serum creatinine was modest and similar in the two treatment groups.
  
  
  CONCLUSIONS
  When administered with penicillin G, tobramycin given once daily was as efficacious and safe as tobramycin given three times daily in cancer patients with febrile neutropenia in Norway, provided the regimen was modified according to the clinical response.
authors.affiliation: Cancer Clinic, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway. dag.torfoss@radiumhospitalet.no
authors.forename: Dag
authors.initials: D
authors.lastname: Torfoss
authors.forename: E Arne
authors.initials: EA
authors.lastname: Høiby
authors.forename: Jon Magnus
authors.initials: JM
authors.lastname: Tangen
authors.forename: Harald
authors.initials: H
authors.lastname: Holte
authors.forename: Kåre
authors.initials: K
authors.lastname: Bø
authors.forename: Peter
authors.initials: P
authors.lastname: Meyer
authors.forename: Kjell
authors.initials: K
authors.lastname: Grøttum
authors.forename: Kjetil
authors.initials: K
authors.lastname: Weyde
authors.forename: Grete Fossum
authors.initials: GF
authors.lastname: Lauritzsen
authors.forename: Berit
authors.initials: B
authors.lastname: Sandstad
authors.forename: Anne-Birgitte
authors.initials: AB
authors.lastname: Jacobsen
authors.forename: Harald
authors.initials: H
authors.lastname: Olsen
authors.forename: Stein
authors.initials: S
authors.lastname: Kvaløy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005334:Fever / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications*; D009664:Norway; D010400:Penicillin G / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D018401:Sample Size; D014031:Tobramycin / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D010400:Penicillin G; D014031:Tobramycin