Trial Information

Tobramycin én Gang Daglig Mot Tre Ganger Daglig, Gitt Med Benzylpenicillin, Til Pasienter Med nøytropen Feber

Prospective randomized Norwegian multicenter clinical trial (11 hospitals) comparing
tobramycin given once a day (new regimen) vs. three times a day (current regimen), with
penicillin G, to cancer patients with febrile neutropenia. Tobramycin half life and
postantibiotic effect is at best 12 hours. It has been questioned if tobramycin once a day
is safe in patients with low levels of granulocytes when it is given with a drug like
penicillin G which is not covering Gram-negative rods. Treatment of febrile neutropenia with
penicillin G and an aminoglycoside is standard of care in Norway, and it is probably a
regimen that is promoting antimicrobial resistance less than a broad spectrum beta-lactam.

Cancer patients 16-70 with febrile neutropenia and signed informed consent could be
randomized. Exclusion criteria were allergy to study medications, increased creatinine/renal
failure, massive ascites, multiple myeloma, treatment with cis-platinum, recent therapy with
aminoglycoside (4 weeks) or other antibiotics (4 days), hemodynamically unstable patients,
pregnant and nursing patients.

Patients were stratified into three groups: Leukemia patients receiving intensive
chemotherapy, lymphoma patients receiving high dose chemotherapy with autologous stem-cell
support and other cancer patients.

Patients were randomized to either tobramycin once or three times a day. Once the patient
was randomized and the first antibiotic dose was given, further antibiotic therapy was up to
the patient's doctor's discretion (not blinded). Everybody received tobramycin 6 mg/kg/day
and penicillin 5 mill. IE four times a day.

The patients were followed until all antibiotic therapy was terminated. Clinical condition
and laboratory test results at time of randomization (new fever) was registered. Response to
therapy, reason for modification of therapy, mortality, duration of neutropenia, maximum
creatinine level, tobramycin serum concentrations, microbiological findings and total
antibiotic consumption were registered.

After external monitoring of all the data the results are currently being made up and will
be available for publication in 2006.

This trial has been conducted independently of the pharmaceutical industry. Grants have been
received from The Norwegian Radium Hospital research fund, The Regional Health Authorities
and The Norwegian Society for Infectious Diseases.