Evidence map›Paper›PMID 19738011›Full record

ArticleAntimicrobial agents and chemotherapy2009

Plectasin shows intracellular activity against Staphylococcus aureus in human THP-1 monocytes and in a mouse peritonitis model.

Karoline Sidelmann Brinch, Anne Sandberg, Pierre Baudoux, Françoise Van Bambeke, Paul M Tulkens, Niels Frimodt-Møller, Niels Høiby, Hans-Henrik Kristensen

Open access · greenAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.3field-weighted citation impact, top 9% 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

28 citing papers in PubMed, 63 citations in OpenAlex.

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  10. Human MAIT Cells Respond toMicroorganisms · 2022
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  11. Effect of NZ2114 againstFrontiers in microbiology · 2022
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  12. Article
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  14. Potent intracellular antibacterial activity of a marine peptide-N6NHApplied microbiology and biotechnology · 2021
    Article
  15. Article
  16. Review
  17. The Role of Macrophages inFrontiers in immunology · 2020
    Review
  18. Article
  19. Article
  20. 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

8 authors at 4 institutions in 2 countries.

Karoline Sidelmann BrinchNovozymes A/S, Anti-Infective Discovery, Krogshøjvej 36, DK-2880 Bagsvaerd, Denmark. kbri@novozymes.com
Anne Sandberg
Pierre Baudoux
Françoise Van Bambeke
Paul M Tulkens
Niels Frimodt-Møller
Niels Høiby
Hans-Henrik Kristensen
UCLouvain · BENovozymes (Denmark) · DKStatens Serum Institut · DKRigshospitalet · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antimicrobial therapy of infections with Staphylococcus aureus can pose a challenge due to slow response to therapy and recurrence of infection. These treatment difficulties can partly be explained by intracellular survival of staphylococci, which is why the intracellular activity of antistaphylococcal compounds has received increased attention within recent years. The intracellular activity of plectasin, an antimicrobial peptide, against S. aureus was determined both in vitro and in vivo. In vitro studies using THP-1 monocytes showed that some intracellular antibacterial activity of plectasin was maintained (maximal relative efficacy [E(max)], 1.0- to 1.3-log reduction in CFU) even though efficacy was inferior to that of extracellular killing (E(max), >4.5-log CFU reduction). Animal studies included a novel use of the mouse peritonitis model, exploiting extra- and intracellular differentiation assays, and assessment of the correlations between activity and pharmacokinetic (PK) parameters. The intracellular activity of plectasin was in accordance with the in vitro studies, with an E(max) of a 1.1-log CFU reduction. The parameter most important for activity was fC(peak)/MIC, where fC(peak) is the free peak concentration. These findings stress the importance of performing studies of extra- and intracellular activity since these features cannot be predicted from traditional MIC and killing kinetic studies. Application of both the THP-1 and the mouse peritonitis models showed that the in vitro results were similar to findings in the in vivo model with respect to demonstration of intracellular activity. Therefore the in vitro model was a good screening model for intracellular activity. However, animal models should be applied if further information on activity, PK/pharmacodynamic parameters, and optimal dosing regimens is required.

Indexed as

Amino Acid SequenceAnimalsCells, CulturedDisease Models, AnimalDose-Response Relationship, DrugFemaleHumansMiceMicrobial Sensitivity TestsMolecular Sequence DataMonocytesPeptidesPeritonitisStaphylococcus aureusPeptidesplectasin

Identifiers

PMID19738011
PMCPMC2772343
OpenAlexW2103069276

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.