© 2003 by Oxford University Press
© 2003 Oxford University Press
ARTICLE |
Randomized Controlled Trial of Once- Versus Thrice-Daily Tobramycin in Febrile Neutropenic Children Undergoing Stem Cell Transplantation
Affiliations of authors: Departments of Pediatrics (LS, UA, MR, JD), Health Policy Management and Evaluation (LS, UA), Otolaryngology (BB), Public Health Sciences (MA), and Faculty of Pharmacy (LLD, A. Taddio), University of Toronto, Toronto, Ontario, Canada; Department of Pediatrics, Divisions of Hematology/Oncology (LS, LLD, MR, TT, JD) and Infectious Disease (UA), Departments of Pharmacy (LLD, A. Taddio, TT) and Communication Disorders (BB), and Program in Population Health Sciences (LS, LLD, A. Taddio, UA, A. Tong), Research Institute, The Hospital for Sick Children, Toronto; and Cancer Quality Council of Ontario Secretariat, Cancer Care Ontario, Toronto (MA).
Correspondence to: Lillian Sung, MD, FRCPC, Division of Hematology/Oncology, Hospital for Sick Children, 555 University Ave., Toronto, Ontario, Canada M5G 1X8 (e-mail: lillian.sung{at}sickkids.ca)
Background: The benefits of aminoglycoside antibiotics, such as tobramycin, administered as a once-daily dose to manage febrile neutropenia, have been demonstrated in many patient populations. However, toxicity and safety data are lacking for pediatric stem cell transplant recipients, who are at especially high risk for aminoglycoside-related toxicity and infectious morbidity. In particular, the relative nephrotoxicity and efficacy of tobramycin administered as a single daily dose or as three daily doses among this patient population is not known. Methods: We conducted a randomized, double-blind controlled study of tobramycin dosing among children 18 years or younger who had fever and neutropenia while undergoing stem cell transplantation. From October 2000 through November 2002, 60 children were randomly assigned to receive intravenous tobramycin, as either a single daily dose (n = 29) or every 8 hours (n = 31), in combination with either piperacillin or ceftazidime (intravenous). Tobramycin doses were adjusted to achieve pharmacokinetic targets. The primary outcome was nephrotoxicity, as represented by the maximal percent increase in serum creatinine concentration throughout the episode of febrile neutropenia relative to the baseline serum creatinine concentration. Efficacy was a secondary outcome and was defined as survival of the episode without modification of the antibacterial regimen. All statistical tests were two-sided. Results: In a modified intent-to-treat analysis, the mean maximal percent increase in serum creatinine concentration was 32% (N = 26) in the once daily dose group and 51% (N = 28) in the every 8 hours dose group (difference = 19%, 95% confidence interval [CI] = 0% to 38%; P = .054). Among patients evaluable for efficacy, 12 (46%) of 26 patients in the once daily dose group and five (19%) of 27 patients in the every 8 hours dose group survived the episode of febrile neutropenia without requiring antibacterial treatment modification (difference = 27%, 95% CI = 4% to 52%; P = .03). There was one death in each group. Conclusions: In febrile neutropenic children undergoing stem cell transplantation, tobramycin may be less nephrotoxic and more efficacious when administered as a once daily dose than when administered every 8 hours.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  W. Lam, J. Tjon, W. Seto, A. Dekker, C. Wong, E. Atenafu, A. Bitnun, V. Waters, Y. Yau, M. Solomon, et al. Pharmacokinetic modelling of a once-daily dosing regimen for intravenous tobramycin in paediatric cystic fibrosis patients J. Antimicrob. Chemother., June 1, 2007; 59(6): 1135 - 1140. [Abstract] [Full Text] [PDF]
|
|