Can therapeutic drug monitoring optimize exposure to piperacillin in febrile neutropenic patients with haematological malignancies? A randomized controlled trial
Journal of Antimicrobial Chemotherapy August 2015 V.70 N.8 P.2369-2375
Fekade Bruck Sime, Michael S. Roberts, Ing Soo Tiong, Julia H. Gardner, Sheila Lehman, Sandra L. Peake, Uwe Hahn, Morgyn S. Warner, and Jason A. Roberts
1School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia
2Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, Australia
3Therapeutics Research Centre, School of Medicine, University of Queensland, Brisbane, Australia
4Department of Haematology/Oncology, The Queen Elizabeth Hospital, Adelaide, Australia
5SA Pathology and the University of Adelaide, Adelaide, Australia
6Department of Intensive Care Medicine, The Queen Elizabeth Hospital, Adelaide, Australia
7Royal Brisbane and Women’s Hospital, Herston, Brisbane, Queensland, Australia
8Burns, Trauma, and Critical Care Research Centre, University of Queensland, Herston, Brisbane, Queensland, Australia
9Institute of Translational Medicine, University of Liverpool, Liverpool, UK
*Corresponding author. Tel: +614-1218-1027; E-mail: firstname.lastname@example.org
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.
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.
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.
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.