Tobramycin once versus three times daily, given with penicillin G, to febrile neutropenic cancer patients in Norway: a prospective, randomized, multicentre trial.
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.
Torfoss
Dag
D
Cancer Clinic, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway. dag.torfoss@radiumhospitalet.no
Høiby
E Arne
EA
Tangen
Jon Magnus
JM
Holte
Harald
H
Bø
Kåre
K
Meyer
Peter
P
Grøttum
Kjell
K
Weyde
Kjetil
K
Lauritzsen
Grete Fossum
GF
Sandstad
Berit
B
Jacobsen
Anne-Birgitte
AB
Olsen
Harald
H
Kvaløy
Stein
S
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
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D010400:Penicillin G; D014031:Tobramycin