Evidence map›Paper›PMID 26349821›Full record

ArticleAntimicrobial agents and chemotherapy2015

Augmented renal clearance implies a need for increased amoxicillin-clavulanic acid dosing in critically ill children.

Pieter A J G De Cock, Joseph F Standing, Charlotte I S Barker, Annick de Jaeger, Evelyn Dhont, Mieke Carlier, Alain G Verstraete, Joris R Delanghe, Hugo Robays, Peter De Paepe

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02456974 (Antibiotic Dosing in Pediatric Intensive Care), which is not on this map. Cited by 45 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 5 pooled it
7.0field-weighted citation impact, top 3% 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.

NCT02456974 recruitingnot on this map

Antibiotic Dosing in Pediatric Intensive Care

Typeobservational_patient_registrySponsorUniversity Hospital, GhentRan2012 to 2027Enrolled640ConditionsPharmacokinetics, Amoxicillin-clavulanate, Piperacillin-tazobactam, VancomycinArmsblood sampling in patients receiving amoxicillin-clavulanate as part of routine clinical care, blood sampling in patients receiving piperacilline-tazobactam as part of routine clinical care., blood sampling in patients receiving vancomycin as part of routine clinical care., blood sampling in patients receiving teicoplanin as part of routine clinical care., blood sampling in patients receiving meropenem as part of routine clinical care.
3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 5 syntheses or guidelines pooled it, 80 citations in OpenAlex.

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  8. Target attainment of cefotaxime in critically ill children with meningococcal septic shock as a model for cefotaxime dosing in severe pediatric sepsis.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2019
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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

10 authors at 3 institutions in 2 countries.

Pieter A J G De CockDepartment of Pharmacy, Ghent University Hospital, Ghent, Belgium Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium Department of Pediatric Intensive Care, Ghent University Hospital, Ghent, Belgium pieter.decock@uzgent.be.
Joseph F StandingInfection, Inflammation and Rheumatology Section, University College London, Institute of Child Health, University College London, London, United Kingdom CoMPLEX, University College London, London, United Kingdom Department of Pharmacy, Great Ormond Street Hospital, London, United Kingdom.
Charlotte I S BarkerInfection, Inflammation and Rheumatology Section, University College London, Institute of Child Health, University College London, London, United Kingdom Paediatric Infectious Diseases Research Group, Institute for Infection and Immunity, St. George's, University of London, London, United Kingdom.
Annick de JaegerDepartment of Pediatric Intensive Care, Ghent University Hospital, Ghent, Belgium.
Evelyn DhontDepartment of Pediatric Intensive Care, Ghent University Hospital, Ghent, Belgium.
Mieke CarlierDepartment of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
Alain G VerstraeteDepartment of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium.
Joris R DelangheDepartment of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium.
Hugo RobaysDepartment of Pharmacy, Ghent University Hospital, Ghent, Belgium.
Peter De PaepeHeymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
Ghent University · BEGhent University Hospital · BEUniversity College London · GB

Funding

Medical Research Council G1002305Medical Research Council MR/M008665/1
6 · The paper itself

Abstract

There is little data available to guide amoxicillin-clavulanic acid dosing in critically ill children. The primary objective of this study was to investigate the pharmacokinetics of both compounds in this pediatric subpopulation. Patients admitted to the pediatric intensive care unit (ICU) in whom intravenous amoxicillin-clavulanic acid was indicated (25 to 35 mg/kg of body weight every 6 h) were enrolled. Population pharmacokinetic analysis was conducted, and the clinical outcome was documented. A total of 325 and 151 blood samples were collected from 50 patients (median age, 2.58 years; age range, 1 month to 15 years) treated with amoxicillin and clavulanic acid, respectively. A three-compartment model for amoxicillin and a two-compartment model for clavulanic acid best described the data, in which allometric weight scaling and maturation functions were added a priori to scale for size and age. In addition, plasma cystatin C and concomitant treatment with vasopressors were identified to have a significant influence on amoxicillin clearance. The typical population values of clearance for amoxicillin and clavulanic acid were 17.97 liters/h/70 kg and 12.20 liters/h/70 kg, respectively. In 32% of the treated patients, amoxicillin-clavulanic acid therapy was stopped prematurely due to clinical failure, and the patient was switched to broader-spectrum antibiotic treatment. Monte Carlo simulations demonstrated that four-hourly dosing of 25 mg/kg was required to achieve the therapeutic target for both amoxicillin and clavulanic acid. For patients with augmented renal function, a 1-h infusion was preferable to bolus dosing. Current published dosing regimens result in subtherapeutic concentrations in the early period of sepsis due to augmented renal clearance, which risks clinical failure in critically ill children, and therefore need to be updated. (This study has been registered at Clinicaltrials.gov as an observational study [NCT02456974].).

Indexed as

AdolescentAmoxicillin-Potassium Clavulanate CombinationAnti-Bacterial AgentsChildChild, PreschoolCritical IllnessFemaleHumansInfantMaleMonte Carlo MethodProspective StudiesSepsisAmoxicillin-Potassium Clavulanate CombinationAnti-Bacterial Agents

Identifiers

PMID26349821
PMCPMC4604416
OpenAlexW1959456820

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.