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Crit Care. 2015 Jan 30;19:28. doi: 10.1186/s13054-015-0750-y.

Are standard doses of piperacillin sufficient for critically ill patients with augmented creatinine clearance?

Author information

1
Department of Intensive Care and Hyperbaric Medicine, The Alfred Hospital, Commercial Road, Melbourne, Victoria, 3181, Australia. a.udy@alfred.org.au.
2
Burns, Trauma, and Critical Care Research Centre, The University of Queensland, Butterfield Street, Brisbane, Queensland, 4029, Australia. j.lipman@uq.edu.au.
3
Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Butterfield Street, Brisbane, Queensland, 4029, Australia. j.lipman@uq.edu.au.
4
Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Butterfield Street, Brisbane, Queensland, 4029, Australia. paul.jarrett@health.qld.gov.au.
5
Statistics Unit, QIMR Berghofer Medical Research Institute, Herston Road, Brisbane, Queensland, 4029, Australia. Kerenaftali.Klein@qimrberghofer.edu.au.
6
Burns, Trauma, and Critical Care Research Centre, The University of Queensland, Butterfield Street, Brisbane, Queensland, 4029, Australia. s.wallis@uq.edu.au.
7
Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Royal Parade, Melbourne, Victoria, 3052, Australia. Kashyap.Patel@monash.edu.
8
Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Royal Parade, Melbourne, Victoria, 3052, Australia. Carl.Kirkpatrick@monash.edu.
9
Burns, Trauma, and Critical Care Research Centre, The University of Queensland, Butterfield Street, Brisbane, Queensland, 4029, Australia. peter.kruger@health.qld.gov.au.
10
Department of Intensive Care Medicine, Princess Alexandra Hospital, Ipswich Road, Brisbane, Queensland, 4102, Australia. peter.kruger@health.qld.gov.au.
11
Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Butterfield Street, Brisbane, Queensland, Australia. david.antibiotics@gmail.com.
12
Centre for Clinical Research, The University of Queensland, Butterfield Street, Brisbane, Queensland, 4029, Australia. david.antibiotics@gmail.com.
13
School of Pharmacy and Medical Sciences, University of South Australia, North Terrace, Adelaide, South Australia, 5000, Australia. m.roberts@uq.edu.au.
14
Burns, Trauma, and Critical Care Research Centre, The University of Queensland, Butterfield Street, Brisbane, Queensland, 4029, Australia. j.roberts2@uq.edu.au.
15
Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Butterfield Street, Brisbane, Queensland, 4029, Australia. j.roberts2@uq.edu.au.

Abstract

INTRODUCTION:

The aim of this study was to explore the impact of augmented creatinine clearance and differing minimum inhibitory concentrations (MIC) on piperacillin pharmacokinetic/pharmacodynamic (PK/PD) target attainment (time above MIC (fT>MIC)) in critically ill patients with sepsis receiving intermittent dosing.

METHODS:

To be eligible for enrolment, critically ill patients with sepsis had to be receiving piperacillin-tazobactam 4.5 g intravenously (IV) by intermittent infusion every 6 hours for presumed or confirmed nosocomial infection without significant renal impairment (defined by a plasma creatinine concentration greater than 171 μmol/L or the need for renal replacement therapy). Over a single dosing interval, blood samples were drawn to determine unbound plasma piperacillin concentrations. Renal function was assessed by measuring creatinine clearance (CLCR). A population PK model was constructed, and the probability of target attainment (PTA) for 50% and 100% fT>MIC was calculated for varying MIC and CLCR values.

RESULTS:

In total, 48 patients provided data. Increasing CLCR values were associated with lower trough plasma piperacillin concentrations (P < 0.01), such that with an MIC of 16 mg/L, 100% fT>MIC would be achieved in only one-third (n = 16) of patients. Mean piperacillin clearance was approximately 1.5-fold higher than in healthy volunteers and correlated with CLCR (r = 0.58, P < 0.01). A reduced PTA for all MIC values, when targeting either 50% or 100% fT>MIC, was noted with increasing CLCR measures.

CONCLUSIONS:

Standard intermittent piperacillin-tazobactam dosing is unlikely to achieve optimal piperacillin exposures in a significant proportion of critically ill patients with sepsis, owing to elevated drug clearance. These data suggest that CLCR can be employed as a useful tool to determine whether piperacillin PK/PD target attainment is likely with a range of MIC values.

PMID:
25632974
PMCID:
PMC4341874
DOI:
10.1186/s13054-015-0750-y
[Indexed for MEDLINE]
Free PMC Article

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