Evidence map›Paper›PMID 35597889›Full record

ArticleThe ISME journal2022

Complex and unexpected outcomes of antibiotic therapy against a polymicrobial infection.

Lydia-Ann J Ghuneim, Ruma Raghuvanshi, Kerri A Neugebauer, Douglas V Guzior, Martin H Christian, Bella Schena, Jeremiah M Feiner, Alicia Castillo-Bahena, Jenna Mielke, Marc McClelland and 4 more

Abstract read
In one paragraph

Article in The ISME journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–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

21 citing papers in PubMed.

  1. Review
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  6. Review
  7. Article
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  11. Article
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  16. Article
  17. Article
  18. Review
  19. Antibiotic resistance in bacterial communities.Current opinion in microbiology · 2023
    Review
  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

14 authors.

Lydia-Ann J GhuneimDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA.ORCID http://orcid.org/0000-0001-7684-9228
Ruma RaghuvanshiDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA.
Kerri A NeugebauerDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA.
Douglas V GuziorDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA.
Martin H ChristianDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA.
Bella SchenaDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA.
Jeremiah M FeinerDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA.
Alicia Castillo-BahenaSpectrum Health West Michigan, Grand Rapids, MI, 49503, USA.
Jenna MielkeDepartment of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Marc McClellandSpectrum Health West Michigan, Grand Rapids, MI, 49503, USA.
Douglas ConradDepartment of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Isaac KlapperDepartment of Mathematics, Temple University, Philadelphia, PA, 19122, USA.
Tianyu ZhangDepartment of Mathematical Sciences, Montana State University, Bozeman, MT, 59717, USA.
Robert A QuinnDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA. quinnrob@msu.edu.ORCID http://orcid.org/0000-0002-9829-3256

Funding

Determining How a Dynamic Microbiome Contributes to Cystic Fibrosis Lung DiseaseR01AI145925 · NIAID · MICHIGAN STATE UNIVERSITY · PI QUINN, ROBERT ANDREW · 2019 to 2022
$2.7M
NIAID NIH HHS R01 AI145925
6 · The paper itself

Abstract

Antibiotics are our primary approach to treating complex infections, yet we have a poor understanding of how these drugs affect microbial communities. To better understand antimicrobial effects on host-associated microbial communities we treated cultured sputum microbiomes from people with cystic fibrosis (pwCF, n = 24) with 11 different antibiotics, supported by theoretical and mathematical modeling-based predictions in a mucus-plugged bronchiole microcosm. Treatment outcomes we identified in vitro that were predicted in silico were: 1) community death, 2) community resistance, 3) pathogen killing, and 4) fermenter killing. However, two outcomes that were not predicted when antibiotics were applied were 5) community profile shifts with little change in total bacterial load (TBL), and 6) increases in TBL. The latter outcome was observed in 17.8% of samples with a TBL increase of greater than 20% and 6.8% of samples with an increase greater than 40%, demonstrating significant increases in community carrying capacity in the presence of an antibiotic. An iteration of the mathematical model showed that TBL increase was due to antibiotic-mediated release of pH-dependent inhibition of pathogens by anaerobe fermentation. These dynamics were verified in vitro when killing of fermenters resulted in a higher community carrying capacity compared to a no antibiotic control. Metagenomic sequencing of sputum samples during antibiotic therapy revealed similar dynamics in clinical samples. This study shows that the complex microbial ecology dictates the outcomes of antibiotic therapy against a polymicrobial infection.

Indexed as

CoinfectionCystic FibrosisAnti-Bacterial AgentsHumansMetagenomeSputumAnti-Bacterial Agents

Identifiers

PMID35597889
PMCPMC9381758

What OpenQuestion holds

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LicenceCC BY
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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.