Evidence map›Paper›PMID 27449542›Full record

ArticleInternational journal of antimicrobial agents2016

Combinatorial pharmacodynamics of polymyxin B and tigecycline against heteroresistant Acinetobacter baumannii.

Gauri G Rao, Neang S Ly, John Diep, Alan Forrest, Jürgen B Bulitta, Patricia N Holden, Roger L Nation, Jian Li, Brian T Tsuji

Open access · greenAbstract read
In one paragraph

Article in International journal of antimicrobial agents, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 18% 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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Carbapenem Resistance inMicroorganisms · 2025
    Review
  6. The challenges of difficult-to-treatClinical microbiology reviews · 2024
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. 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

9 authors at 4 institutions in 2 countries.

Gauri G RaoSchool of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA. Electronic address: gaurirao@buffalo.edu.
Neang S LyClinical Pharmacology & DMPK, MedImmune LLC, Mountain View, CA, USA.
John DiepSchool of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA.
Alan ForrestUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jürgen B BulittaDepartment of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL, USA.
Patricia N HoldenLaboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA; The New York State Center of Excellence in Bioinformatics & Life Sciences, University at Buffalo, SUNY, Buffalo, NY, USA.
Roger L NationFacility for Anti-Infective Drug Development and Innovation, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
Jian LiFacility for Anti-Infective Drug Development and Innovation, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
Brian T TsujiLaboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA; The New York State Center of Excellence in Bioinformatics & Life Sciences, University at Buffalo, SUNY, Buffalo, NY, USA. Electronic address: btsuji@buffalo.edu.
University at Buffalo, State University of New York · USMonash University · AUUniversity of Florida · USUniversity of North Carolina at Chapel Hill · US

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
NIAID NIH HHS R01 AI111990
6 · The paper itself

Abstract

The prevalence of heteroresistant Acinetobacter baumannii is increasing. Infections due to these resistant pathogens pose a global treatment challenge. Here, the pharmacodynamic activities of polymyxin B (PMB) (2-20 mg/L) and tigecycline (0.15-4 mg/L) were evaluated as monotherapy and in combination using a 4 × 4 concentration array against two carbapenem-resistant and polymyxin-heteroresistant A. baumannii isolates. Time Kill Experiments was employed at starting inocula of 10(6) and 10(8) CFU/mL over 48 h. Clinically relevant combinations of PMB (2 mg/L) and tigecycline (0.90 mg/L) resulted in greater reductions in the bacterial population compared with polymyxin alone by 8 h (ATCC 19606, -6.38 vs. -3.43 log10 CFU/mL; FADDI AB115, -1.38 vs. 2.08 log10 CFU/mL). At 10× the clinically achievable concentration (PMB 20 mg/L in combination with tigecycline 0.90 mg/L), there was bactericidal activity against FADDI AB115 by 4 h that was sustained until 32 h, and against ATCC 19606 that was sustained for 48 h. These studies show that aggressive polymyxin-based dosing in combination with clinically achievable tigecycline concentrations results in early synergistic activity that is not sustained beyond 8 h, whereas combinations with higher tigecycline concentrations result in sustained bactericidal activity against both isolates at both inocula. These results indicate a need for optimised front-loaded polymyxin-based combination regimens that utilise high polymyxin doses at the onset of treatment to achieve good pharmacodynamic activity whilst minimising adverse events.

Indexed as

Drug Resistance, BacterialDrug SynergismAcinetobacter baumanniiAnti-Bacterial AgentsMicrobial Sensitivity TestsMicrobial ViabilityMinocyclinePolymyxin BTigecyclineTime FactorsAnti-Bacterial AgentsMinocyclinePolymyxin BTigecyclineAcinetobacter baumanniiCombinationsPharmacodynamicsPolymyxin BPolymyxinsTigecycline

Identifiers

PMID27449542
PMCPMC5256686
OpenAlexW2463386561

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.