Evidence map›Paper›PMID 30624656›Full record

ArticleThe Journal of antimicrobial chemotherapy2019

Pharmacokinetic-pharmacodynamic modelling to investigate in vitro synergy between colistin and fusidic acid against MDR Acinetobacter baumannii.

Lynette M Phee, Frank Kloprogge, Rebecca Morris, John Barrett, David W Wareham, Joseph F Standing

Open access · hybridAbstract read
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. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
0.2field-weighted citation impact, top 59% 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

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
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

6 authors at 3 institutions in 1 country.

Lynette M PheeCentre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK.
Frank KloproggeGreat Ormond Street Institute of Child Health, University College London, London, UK.
Rebecca MorrisMedicines Research Centre, GlaxoSmithKline, Stevenage, UK.
John BarrettMedicines Research Centre, GlaxoSmithKline, Stevenage, UK.
David W WarehamCentre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK.
Joseph F StandingGreat Ormond Street Institute of Child Health, University College London, London, UK.
GlaxoSmithKline (United Kingdom) · GBGreat Ormond Street Hospital · GBQueen Mary University of London · GB

Funding

Department of HealthMedical Research Council MR/M008665/1Medical Research Council MR/P014534/1
6 · The paper itself

Abstract

objectivesThe potential for synergy between colistin and fusidic acid in the treatment of MDR Acinetobacter baumannii has recently been shown. The aim of this study was to perform an extensive in vitro characterization of this effect using pharmacokinetic-pharmacodynamic modelling (PKPD) of time-kill experiments in order to estimate clinical efficacy.

methodsFor six clinical strains, 312 individual time-kill experiments were performed including 113 unique pathogen-antimicrobial combinations. A wide range of concentrations (0.25-8192 mg/L for colistin and 1-8192 mg/L for fusidic acid) were explored, alone and in combination. PKPD modelling sought to quantify synergistic effects.

resultsA PKPD model confirmed synergy in that colistin EC50 was found to decrease by 83% in the presence of fusidic acid, and fusidic acid maximum increase in killing rate (Emax) also increased 58% in the presence of colistin. Simulations indicated, however, that at clinically achievable free concentrations, the combination may be bacteriostatic in colistin-susceptible strains, but growth inhibition probability was <20% in a colistin-resistant strain.

conclusionsFusidic acid may be a useful agent to add to colistin in a multidrug combination for MDR Acinetobacter baumannii.

Indexed as

Drug SynergismAcinetobacter baumanniiAcinetobacter InfectionsAnti-Bacterial AgentsColistinFusidic AcidHumansMicrobial ViabilityModels, TheoreticalAnti-Bacterial AgentsColistinFusidic Acid

Identifiers

PMID30624656
PMCPMC6419616
OpenAlexW2910419422

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.