Can therapeutic drug monitoring optimize exposure to piperacillin in febrile neutropenic patients with haematological malignancies? A randomized controlled trial

Sime, Fekade B., Roberts, Michael S., Tiong, Ing S., Gardner, Julia H., Lehman, Sheila, Peake, Sandra L., Hahn, Uwe, Warner, Morgyn S. and Roberts, Jason A. (2015) Can therapeutic drug monitoring optimize exposure to piperacillin in febrile neutropenic patients with haematological malignancies? A randomized controlled trial. Journal of Antimicrobial Chemotherapy, 70 8: 2369-2375. doi:10.1093/jac/dkv123


Author Sime, Fekade B.
Roberts, Michael S.
Tiong, Ing S.
Gardner, Julia H.
Lehman, Sheila
Peake, Sandra L.
Hahn, Uwe
Warner, Morgyn S.
Roberts, Jason A.
Title Can therapeutic drug monitoring optimize exposure to piperacillin in febrile neutropenic patients with haematological malignancies? A randomized controlled trial
Journal name Journal of Antimicrobial Chemotherapy   Check publisher's open access policy
ISSN 1460-2091
0305-7453
Publication date 2015-05-07
Year available 2015
Sub-type Article (original research)
DOI 10.1093/jac/dkv123
Open Access Status Not Open Access
Volume 70
Issue 8
Start page 2369
End page 2375
Total pages 7
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Subject 3004 Pharmacology
2736 Pharmacology (medical)
2725 Infectious Diseases
Abstract Objectives: The objectives of this study were to describe piperacillin exposure in febrile neutropenia patients and determine whether therapeutic drug monitoring (TDM) can be used to increase the achievement of pharmacokinetic (PK)/pharmacodynamic (PD) targets.
Formatted abstract
Objectives:  The objectives of this study were to describe piperacillin exposure in febrile neutropenia patients and determine whether therapeutic drug monitoring (TDM) can be used to increase the achievement of pharmacokinetic (PK)/pharmacodynamic (PD) targets.

Methods:  In a prospective randomized controlled study (Australian New Zealand Registry, ACTRN12615000086561), patients were subjected to TDM for 3 consecutive days. Dose was adjusted in the intervention group to achieve a free drug concentration above the MIC for 100% of the dose interval (100% fT>MIC), which was also the primary outcome measure. The secondary PK/PD target was 50% fT>MIC. Duration of fever and days to recovery from neutropenia were recorded.

Results:  Thirty-two patients were enrolled. Initially, patients received 4.5 g of piperacillin/tazobactam every 8 h or every 6 h along with gentamicin co-therapy in 30/32 (94%) patients. At the first TDM, 7/32 (22%) patients achieved 100% fT>MIC and 12/32 (38%) patients achieved 50% fT>MIC. Following dose adjustment, 11/16 (69%) of intervention patients versus 3/16 (19%) of control patients (P = 0.012) attained 100% fT>MIC, and 15/16 (94%) of intervention patients versus 5/16 (31%) of control patients (P = 0.001) achieved 50% fT>MIC. After the third TDM, the proportion of patients attaining 100% fT>MIC improved from a baseline 3/16 (19%) to 11/15 (73%) in the intervention group, while it declined from 4/16 (25%) to 1/15 (7%) in the control group. No difference was noted in the duration of fever and days to recovery from neutropenia.

Conclusions:  Conventional doses of piperacillin/tazobactam may not offer adequate piperacillin exposure in febrile neutropenic patients. TDM provides useful feedback of dosing adequacy to guide dose optimization.
Keyword Pharmacodynamics
Pharmacokinetics
β-lactams
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID APP1048652
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
School of Pharmacy Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
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