Evidence map›Paper›PMID 21911563›Full record

ArticleAntimicrobial agents and chemotherapy2011

Synergistic killing of multidrug-resistant Pseudomonas aeruginosa at multiple inocula by colistin combined with doripenem in an in vitro pharmacokinetic/pharmacodynamic model.

Phillip J Bergen, Brian T Tsuji, Jurgen B Bulitta, Alan Forrest, Jovan Jacob, Hanna E Sidjabat, David L Paterson, Roger L Nation, Jian Li

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 2 pooled it
2.9field-weighted citation impact, top 8% 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

61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 115 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. DynamicAntibiotics (Basel, Switzerland) · 2024
    Review
  5. Article
  6. Article
  7. Article
  8. Age of Antibiotic Resistance in MDR/XDR Clinical Pathogen ofPharmaceuticals (Basel, Switzerland) · 2023
    Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

1 more citing papers are in PubMed but not listed here.

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.

Phillip J BergenDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia.
Brian T Tsuji
Jurgen B Bulitta
Alan Forrest
Jovan Jacob
Hanna E Sidjabat
David L Paterson
Roger L Nation
Jian Li
Monash University · AUUniversity at Buffalo, State University of New York · USRoyal Brisbane and Women's Hospital · AUUniversity of Queensland · AU

Funding

Targeting MDR hetero-resistant Gram-negatives: PK/PD for rational combinationsR01AI079330 · NIAID · MONASH UNIVERSITY · PI NATION, ROGER L. · 2008 to 2011
$2.2M
NIAID NIH HHS R01 AI079330NIAID NIH HHS R01AI079330
6 · The paper itself

Abstract

Combination therapy may be required for multidrug-resistant (MDR) Pseudomonas aeruginosa. The aim of this study was to systematically investigate bacterial killing and emergence of colistin resistance with colistin and doripenem combinations against MDR P. aeruginosa. Studies were conducted in a one-compartment in vitro pharmacokinetic/pharmacodynamic model for 96 h at two inocula (~10(6) and ~10(8) CFU/ml) against a colistin-heteroresistant reference strain (ATCC 27853) and a colistin-resistant MDR clinical isolate (19147 n/m). Four combinations utilizing clinically achievable concentrations were investigated. Microbiological response was examined by log changes and population analysis profiles. Colistin (constant concentrations of 0.5 or 2 mg/liter) plus doripenem (peaks of 2.5 or 25 mg/liter every 8 h; half-life, 1.5 h) substantially increased bacterial killing against both strains at the low inoculum, while combinations containing colistin at 2 mg/liter increased activity against ATCC 27853 at the high inoculum; only colistin at 0.5 mg/liter plus doripenem at 2.5 mg/liter failed to improve activity against 19147 n/m at the high inoculum. Combinations were additive or synergistic against ATCC 27853 in 16 and 11 of 20 cases (4 combinations across 5 sample points) at the 10(6)- and 10(8)-CFU/ml inocula, respectively; the corresponding values for 19147 n/m were 16 and 9. Combinations containing doripenem at 25 mg/liter resulted in eradication of 19147 n/m at the low inoculum and substantial reductions in regrowth (including to below the limit of detection at ∼50 h) at the high inoculum. Emergence of colistin-resistant subpopulations of ATCC 27853 was substantially reduced and delayed with combination therapy. This investigation provides important information for optimization of colistin-doripenem combinations.

Indexed as

Drug Resistance, Multiple, BacterialAnti-Bacterial AgentsCarbapenemsColistinColony Count, MicrobialCystic FibrosisDoripenemDrug SynergismDrug Therapy, CombinationHalf-LifeHumansModels, BiologicalPseudomonas aeruginosaPseudomonas InfectionsAnti-Bacterial AgentsCarbapenemsColistinDoripenem

Identifiers

PMID21911563
PMCPMC3232764
OpenAlexW2127422236

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.