Evidence map›Paper›PMID 26926641›Full record

ArticleAntimicrobial agents and chemotherapy2016

Optimization of Polymyxin B in Combination with Doripenem To Combat Mutator Pseudomonas aeruginosa.

Neang S Ly, Zackery P Bulman, Jürgen B Bulitta, Christopher Baron, Gauri G Rao, Patricia N Holden, Jian Li, Mark D Sutton, Brian T Tsuji

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

12 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Guideline
  2. Article
  3. Article
  4. Article
  5. Review
  6. PKPD Modeling of the Inoculum Effect ofFrontiers in pharmacology · 2022
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Synergistic combinations of polymyxins.International journal of antimicrobial agents · 2016
    Review
  12. 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

9 authors.

Neang S LyLaboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA The New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.ORCID 0000-0002-5571-0347
Zackery P BulmanLaboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA The New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.
Jürgen B BulittaDepartment of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, Florida, USA.
Christopher BaronDepartment of Biochemistry, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.
Gauri G RaoLaboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA The New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.
Patricia N HoldenLaboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA The New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.
Jian LiDrug Delivery, Disposition, and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia.
Mark D SuttonDepartment of Biochemistry, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.
Brian T TsujiLaboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA The New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA btsuji@buffalo.edu.

Funding

Novel PK/PD Strategies for Polymyxin Combinations against Gram-negative SuperbugsR01AI111990 · NIAID · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI LI, JIAN, TSUJI, BRIAN · 2014 to 2018
$4.4M
Regulation of DNA Replication and RepairR01GM066094 · NIGMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI SUTTON, MARK D. · 2003 to 2016
$4.0M
NIAID NIH HHS R01 AI111990NIGMS NIH HHS R01 GM066094
6 · The paper itself

Abstract

Development of spontaneous mutations in Pseudomonas aeruginosa has been associated with antibiotic failure, leading to high rates of morbidity and mortality. Our objective was to evaluate the pharmacodynamics of polymyxin B combinations against rapidly evolving P. aeruginosa mutator strains and to characterize the time course of bacterial killing and resistance via mechanism-based mathematical models. Polymyxin B or doripenem alone and in combination were evaluated against six P. aeruginosa strains: wild-type PAO1, mismatch repair (MMR)-deficient (mutS and mutL) strains, and 7,8-dihydro-8-oxo-deoxyguanosine system (GO) base excision repair (BER)-deficient (mutM, mutT, and mutY) strains over 48 h. Pharmacodynamic modeling was performed using S-ADAPT and facilitated by SADAPT-TRAN. Mutator strains displayed higher mutation frequencies than the wild type (>600-fold). Exposure to monotherapy was followed by regrowth, even at high polymyxin B concentrations of up to 16 mg/liter. Polymyxin B and doripenem combinations displayed enhanced killing activity against all strains where complete eradication was achieved for polymyxin B concentrations of >4 mg/liter and doripenem concentrations of 8 mg/liter. Modeling suggested that the proportion of preexisting polymyxin B-resistant subpopulations influenced the pharmacodynamic profiles for each strain uniquely (fraction of resistance values are -8.81 log10 for the wild type, -4.71 for the mutS mutant, and -7.40 log10 for the mutM mutant). Our findings provide insight into the optimization of polymyxin B and doripenem combinations against P. aeruginosa mutator strains.

Indexed as

Anti-Bacterial AgentsBacterial ProteinsCarbapenemsDoripenemDrug SynergismMicrobial Sensitivity TestsMutationPolymyxin BPseudomonas aeruginosaAnti-Bacterial AgentsBacterial ProteinsCarbapenemsDoripenemPolymyxin B

Identifiers

PMID26926641
PMCPMC4862466

What OpenQuestion holds

Textmetadata
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.