Evidence map›Paper›PMID 33824337›Full record

ArticleNPJ biofilms and microbiomes2021

Treatment with a neutrophil elastase inhibitor and ofloxacin reduces P. aeruginosa burden in a mouse model of chronic suppurative otitis media.

K M Khomtchouk, L I Joseph, B B Khomtchouk, A Kouhi, S Massa, A Xia, I Koliesnik, D Pletzer, P L Bollyky, P L Santa Maria

Open access · goldAbstract readComparative Study
In one paragraph

Article in NPJ biofilms and microbiomes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

11 citing papers in PubMed, 19 citations in OpenAlex.

  1. Review
  2. Management Strategies for Chronic Suppurative Otitis Media and Why They Fail.Journal of the Association for Research in Otolaryngology : JARO · 2025
    Review
  3. Article
  4. Article
  5. Fluoroquinolones and Biofilm: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2024
    Review
  6. Biologics : targets & therapy · 2024
    Article
  7. Evaluation of the Current Bacterial Pathogens and Antibiogram of Chronic Suppurative Otitis Media in Adults.Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India · 2023
    Article
  8. Article
  9. Article
  10. Article
  11. 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

10 authors at 5 institutions in 3 countries.

K M Khomtchouk *Department of Otolaryngology, Head and Neck Surgery, Stanford University, Stanford, CA, USA.ORCID 0000-0001-6241-8558
L I Joseph *Department of Otolaryngology, Head and Neck Surgery, Stanford University, Stanford, CA, USA.ORCID 0000-0001-6803-4619
B B KhomtchoukDepartment of Medicine, Section of Computational Biomedicine and Biomedical Data Science, University of Chicago, Chicago, IL, USA.
A KouhiDepartment of Otolaryngology, Head and Neck Surgery, Tehran University of Medical Sciences, Tehran, Iran.ORCID 0000-0002-4154-8908
S MassaDepartment of Otolaryngology, Head and Neck Surgery, Stanford University, Stanford, CA, USA.
A XiaDepartment of Otolaryngology, Head and Neck Surgery, Stanford University, Stanford, CA, USA.
I KoliesnikDepartment of Medicine, Infectious Diseases, Stanford University, Stanford, CA, USA.
D PletzerDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.ORCID 0000-0001-5750-7505
P L BollykyDepartment of Medicine, Infectious Diseases, Stanford University, Stanford, CA, USA.ORCID 0000-0003-2499-9448
P L Santa MariaDepartment of Otolaryngology, Head and Neck Surgery, Stanford University, Stanford, CA, USA. petersantamaria@stanford.edu.
Stanford University · USStanford Medicine · USTehran University of Medical Sciences · IRUniversity of Chicago · USUniversity of Otago · NZ

Funding

BD Canto II RUO CytometerS10RR027431 · NCRR · STANFORD UNIVERSITY · PI NOLAN, GARRY P · 2010 to 2010
$236k
NCRR NIH HHS S10 RR027431
6 · The paper itself

Abstract

Chronic suppurative otitis media (CSOM) is a widespread, debilitating problem with poorly understood immunology. Here, we assess the host response to middle ear infection over the course of a month post-infection in a mouse model of CSOM and in human subjects with the disease. Using multiparameter flow cytometry and a binomial generalized linear machine learning model, we identified Ly6G, a surface marker of mature neutrophils, as the most informative factor of host response driving disease in the CSOM mouse model. Consistent with this, neutrophils were the most abundant cell type in infected mice and Ly6G expression tracked with the course of infection. Moreover, neutrophil-specific immunomodulatory treatment using the neutrophil elastase inhibitor GW 311616A significantly reduces bacterial burden relative to ofloxacin-only treated animals in this model. The levels of dsDNA in middle ear effusion samples are elevated in both humans and mice with CSOM and decreased during treatment, suggesting that dsDNA may serve as a molecular biomarker of treatment response. Together these data strongly implicate neutrophils in the ineffective immune response to P. aeruginosa infection in CSOM and suggest that immunomodulatory strategies may benefit drug-tolerant infections for chronic biofilm-mediated disease.

Indexed as

AnimalsAntigens, LyDisease Models, AnimalDrug SynergismFemaleFlow CytometryHumansMachine LearningMaleMiceNeutrophilsOfloxacinOtitis Media, SuppurativePiperidinesProteinase Inhibitory Proteins, SecretoryPseudomonas aeruginosaAntigens, LyGW 311616Ly6G antigen, mouseOfloxacinPiperidinesProteinase Inhibitory Proteins, Secretory

Identifiers

PMID33824337
PMCPMC8024339
OpenAlexW3142661008

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.