Evidence map›Paper›PMID 31273375›Full record

ArticleThe Journal of antimicrobial chemotherapy2019

Population pharmacokinetics of piperacillin in febrile children receiving cancer chemotherapy: the impact of body weight and target on an optimal dosing regimen.

Anders Thorsted, Anders N Kristoffersson, Sabine F Maarbjerg, Henrik Schrøder, Mikala Wang, Birgitte Brock, Elisabet I Nielsen, Lena E Friberg

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

8 citing papers in PubMed, 15 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Anders ThorstedDepartment of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Anders N KristofferssonDepartment of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Sabine F MaarbjergDepartment of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.
Henrik SchrøderDepartment of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.
Mikala WangDepartment of Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark.
Birgitte BrockDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
Elisabet I NielsenDepartment of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Lena E FribergDepartment of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Aarhus University Hospital · DKUppsala University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe β-lactam antibiotic piperacillin (in combination with tazobactam) is commonly chosen for empirical treatment of suspected bacterial infections. However, pharmacokinetic variability among patient populations and across ages leads to uncertainty when selecting a dosing regimen to achieve an appropriate pharmacodynamic target.

objectivesTo guide dosing by establishing a population pharmacokinetic model for unbound piperacillin in febrile children receiving cancer chemotherapy, and to assess pharmacokinetic/pharmacodynamic target attainment (100% fT > 1×MIC and 50% fT > 4×MIC) and resultant exposure, across body weights.

methodsForty-three children admitted for 89 febrile episodes contributed 482 samples to the pharmacokinetic analysis. The typical doses required for target attainment were compared for various dosing regimens, in particular prolonged infusions, across MICs and body weights.

resultsA two-compartment model with inter-fever-episode variability in CL, and body weight included through allometry, described the data. A high CL of 15.4 L/h (70 kg) combined with high glomerular filtration rate (GFR) values indicated rapid elimination and hyperfiltration. The target of 50% fT > 4×MIC was achieved for an MIC of 4.0 mg/L in a typical patient with extended infusions of 2-3 (q6h) or 3-4 (q8h) h, at or below the standard adult dose (75 and 100 mg/kg/dose for q6h and q8h, respectively). Higher doses or continuous infusion were needed to achieve 100% fT > 1×MIC due to the rapid piperacillin elimination.

conclusionsThe licensed dose for children with febrile neutropenia (80 mg/kg q6h as a 30 min infusion) performs poorly for attainment of fT>MIC pharmacokinetic/pharmacodynamic targets. Given the population pharmacokinetic profile, feasible dosing regimens with reasonable exposure are continuous infusion (100% fT > 1×MIC) or prolonged infusions (50% fT > 4×MIC).

Indexed as

AdolescentAnti-Bacterial AgentsBacterial InfectionsBody WeightChildChild, PreschoolFemaleFeverGlomerular Filtration RateHumansInfantMaleMicrobial Sensitivity TestsNeoplasmsPiperacillinPiperacillin, Tazobactam Drug CombinationAnti-Bacterial AgentsPiperacillinPiperacillin, Tazobactam Drug CombinationTazobactam

Identifiers

PMID31273375
PMCPMC6916132
OpenAlexW2954084417

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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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.