Tobramycin once versus three times daily, given with penicillin G, to febrile neutropenic cancer patients in Norway: a prospective, randomized, multicentre trial

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.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.modification of the antibiotic regimen.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.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.