Evidence map›Paper›PMID 25632974›Full record

ArticleCritical care (London, England)2015

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

Andrew A Udy, Jeffrey Lipman, Paul Jarrett, Kerenaftali Klein, Steven C Wallis, Kashyap Patel, Carl M J Kirkpatrick, Peter S Kruger, David L Paterson, Michael S Roberts and 1 more

Open access · goldAbstract read
In one paragraph

Article in Critical care (London, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 1 pooled it
15.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

67 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.

  1. Pooled it
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7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 7 institutions in 1 country.

Andrew A UdyDepartment of Intensive Care and Hyperbaric Medicine, The Alfred Hospital, Commercial Road, Melbourne, Victoria, 3181, Australia. a.udy@alfred.org.au.
Jeffrey LipmanBurns, Trauma, and Critical Care Research Centre, The University of Queensland, Butterfield Street, Brisbane, Queensland, 4029, Australia. j.lipman@uq.edu.au.
Paul JarrettDepartment of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Butterfield Street, Brisbane, Queensland, 4029, Australia. paul.jarrett@health.qld.gov.au.
Kerenaftali KleinStatistics Unit, QIMR Berghofer Medical Research Institute, Herston Road, Brisbane, Queensland, 4029, Australia. Kerenaftali.Klein@qimrberghofer.edu.au.
Steven C WallisBurns, Trauma, and Critical Care Research Centre, The University of Queensland, Butterfield Street, Brisbane, Queensland, 4029, Australia. s.wallis@uq.edu.au.
Kashyap PatelFaculty of Pharmacy and Pharmaceutical Sciences, Monash University, Royal Parade, Melbourne, Victoria, 3052, Australia. Kashyap.Patel@monash.edu.
Carl M J KirkpatrickFaculty of Pharmacy and Pharmaceutical Sciences, Monash University, Royal Parade, Melbourne, Victoria, 3052, Australia. Carl.Kirkpatrick@monash.edu.
Peter S KrugerBurns, Trauma, and Critical Care Research Centre, The University of Queensland, Butterfield Street, Brisbane, Queensland, 4029, Australia. peter.kruger@health.qld.gov.au.
David L PatersonDepartment of Infectious Diseases, Royal Brisbane and Women's Hospital, Butterfield Street, Brisbane, Queensland, Australia. david.antibiotics@gmail.com.
Michael S RobertsSchool of Pharmacy and Medical Sciences, University of South Australia, North Terrace, Adelaide, South Australia, 5000, Australia. m.roberts@uq.edu.au.
Jason A RobertsBurns, Trauma, and Critical Care Research Centre, The University of Queensland, Butterfield Street, Brisbane, Queensland, 4029, Australia. j.roberts2@uq.edu.au.
The University of Queensland · AUMonash University · AURoyal Brisbane and Women's Hospital · AUPrincess Alexandra Hospital · AUQIMR Berghofer Medical Research Institute · AUThe Alfred Hospital · AUUniversity of South Australia · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThe 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.

methodsTo 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.

resultsIn 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.

conclusionsStandard 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.

Indexed as

Metabolic Clearance RateAdultAgedAnti-Bacterial AgentsCreatinineCritical IllnessFemaleHumansKidney Function TestsMalePiperacillinRenal Replacement TherapyAnti-Bacterial AgentsCreatininePiperacillin

Identifiers

PMID25632974
PMCPMC4341874
OpenAlexW1998853564

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.