Evidence map›Paper›PMID 37380093›Full record

ArticleInternational journal of antimicrobial agents2023

Model-informed dose optimisation of polymyxin-rifampicin combination therapy against multidrug-resistant Acinetobacter baumannii.

Jinxin Zhao, Yan Zhu, Mei-Ling Han, Jing Lu, Heidi H Yu, Hasini Wickremasinghe, Qi Tony Zhou, Phillip Bergen, Gauri Rao, Tony Velkov and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of antimicrobial agents, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.3field-weighted citation impact, top 54% 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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. Article
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

12 authors at 5 institutions in 2 countries.

Jinxin ZhaoMonash Biomedicine Discovery Institute, Infection Program and Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Yan ZhuMonash Biomedicine Discovery Institute, Infection Program and Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Mei-Ling HanMonash Biomedicine Discovery Institute, Infection Program and Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Jing LuMonash Biomedicine Discovery Institute, Infection Program and Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Heidi H YuMonash Biomedicine Discovery Institute, Infection Program and Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Hasini WickremasingheMonash Biomedicine Discovery Institute, Infection Program and Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Qi Tony ZhouDepartment of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana.
Phillip BergenMonash Biomedicine Discovery Institute, Infection Program and Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Gauri RaoDivision of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina.
Tony VelkovDepartment of Biochemistry and Pharmacology, The University of Melbourne, Melbourne, Victoria, Australia.
Yu-Wei LinMonash Biomedicine Discovery Institute, Infection Program and Department of Microbiology, Monash University, Clayton, Victoria, Australia. Electronic address: yu-wei.lin@monash.edu.
Jian LiMonash Biomedicine Discovery Institute, Infection Program and Department of Microbiology, Monash University, Clayton, Victoria, Australia. Electronic address: jian.li@monash.edu.
Australian Regenerative Medicine Institute · AUDiscovery Institute · USPurdue University West Lafayette · USThe University of Melbourne · AUUniversity of North Carolina at Chapel Hill · US

Funding

Combating Deadly Gram-negative Lung Infections: An Inhalation and Systems ApproachR01AI132681 · NIAID · PURDUE UNIVERSITY · PI LI, JIAN, ZHOU, QI · 2017 to 2020
$2.4M
NIAID NIH HHS R01 AI132681
6 · The paper itself

Abstract

objectivesAntimicrobial resistance is a major global threat. Because of the stagnant antibiotic pipeline, synergistic antibiotic combination therapy has been proposed to treat rapidly emerging multidrug-resistant (MDR) pathogens. We investigated antimicrobial synergy of polymyxin/rifampicin combination against MDR Acinetobacter baumannii.

methodsIn vitro static time-kill studies were performed over 48 h at an initial inoculum of ∼10

resultsPolymyxin B and rifampicin alone produced initial killing against MDR A. baumannii but were associated with extensive regrowth. Notably, the combination showed synergistic killing across all three A. baumannii isolates with bacterial loads below the limit of quantification for up to 48 h. Membrane integrity assays confirmed the role of polymyxin-driven outer membrane remodelling in the observed synergy. Subsequently, the mechanism of synergy was incorporated into a PK/PD model to describe the enhanced uptake of rifampicin due to polymyxin-induced membrane permeabilisation. Simulations with clinically utilised dosing regimens confirmed the therapeutic potential of this combination, particularly in the prevention of bacterial regrowth. Finally, results from a neutropenic mouse thigh infection model confirmed the in vivo synergistic killing of the combination against A. baumannii AB5075.

conclusionOur results showed that polymyxin B combined with rifampicin is a promising option to treat bloodstream and tissue infection caused by MDR A. baumannii and warrants clinical evaluations.

Indexed as

Acinetobacter baumanniiPolymyxin BAnimalsAnti-Bacterial AgentsDrug Resistance, Multiple, BacterialDrug SynergismMiceMicrobial Sensitivity TestsPolymyxinsRifampinAnti-Bacterial AgentsPolymyxin BPolymyxinsRifampinModel-informed dose optimisationMultidrug-resistant Acinetobacter baumanniiPharmacokinetics/pharmacodynamicsPolymyxinRifampicinSemi-mechanistic PK/PD model

Identifiers

PMID37380093
PMCPMC11608097
OpenAlexW4382051238

What OpenQuestion holds

Textmetadata
LicenceTDM
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.