Evidence map›Paper›PMID 39435664›Full record

ArticleJCI insight2024

The contribution of neutrophils to bacteriophage clearance and pharmacokinetics in vivo.

Arne Echterhof, Tejas Dharmaraj, Arya Khosravi, Robert McBride, Lynn Miesel, Ju-Hsin Chia, Patrick M Blankenberg, Kun-Yuan Lin, Chien-Chang Shen, Yu-Ling Lee and 7 more

Abstract read
In one paragraph

Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

  1. Article
  2. Pharmacology of Bacteriophage Therapy in Children: A Re-Emerging Paradigm in Antibacterial Therapy.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2026
    Article
  3. Review
  4. Immune Responses to Phage Therapy in Humans: A Review.The Journal of infectious diseases · 2026
    Review
  5. Phage-Based Approaches to ChronicAntibiotics (Basel, Switzerland) · 2026
    Review
  6. Review
  7. Whole-body distribution of threeAntimicrobial agents and chemotherapy · 2026
    Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Arne EchterhofDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Tejas DharmarajDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Arya KhosraviDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Robert McBrideFelix Biotechnology, South San Francisco, California, USA.
Lynn MieselPharmacology Discovery Services, Taipei, Taiwan.
Ju-Hsin ChiaPharmacology Discovery Services, Taipei, Taiwan.
Patrick M BlankenbergDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Kun-Yuan LinPharmacology Discovery Services, Taipei, Taiwan.
Chien-Chang ShenPharmacology Discovery Services, Taipei, Taiwan.
Yu-Ling LeePharmacology Discovery Services, Taipei, Taiwan.
Yu-Chuan YehPharmacology Discovery Services, Taipei, Taiwan.
Wei Ting LiaoPharmacology Discovery Services, Taipei, Taiwan.
Francis G BlankenbergDivision of Pediatric Radiology and Nuclear Medicine, Department of Radiology, Lucile Packard Children's Hospital, Stanford, California, USA.
Krystyna DąbrowskaLaboratory of Phage Molecular Biology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
Derek F AmanatullahDepartment of Orthopedic Surgery, Stanford University School of Medicine, Stanford, California, USA.
Adam R FrymoyerDivision of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California, USA.
Paul L BollykyDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007365 · NIGMS · STANFORD UNIVERSITY · PI CHUA, KATRIN F · 1985 to 2021
$33.8M
EMERGING INFECTIOUS DISEASEST32AI007502 · NIAID · STANFORD UNIVERSITY · PI Prasanna Jagannathan, DAVID A. RELMAN · 1995 to 2026
$6.8M
The role of macrophages in chronic suppurative otitis media associated sensory hearing lossR01DC019965 · NIDCD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Peter Luke Santa Maria · 2022 to 2026
$3.6M
Stanford ChEM-H Chemistry/Biology Interface Predoctoral Training ProgramT32GM139791 · NIGMS · STANFORD UNIVERSITY · PI Carolyn Bertozzi, Christine Jacobs-Wagner · 2021 to 2026
$2.4M
Non-invasive Monitoring for Infections and Rejection after Lung TransplantationR01AI182349 · NIAID · STANFORD UNIVERSITY · PI Paul L Bollyky · 2024 to 2026
$1.8M
Pathogenesis of Pf Bacteriophages in Pseudomonas Cystic Fibrosis lung InfectionsR01HL148184 · NHLBI · STANFORD UNIVERSITY · PI MILLA, CARLOS · 2019 to 2022
$1.7M
Studies on bacteriophages in respiratory diseasesK24AI166718 · NIAID · STANFORD UNIVERSITY · PI Paul L Bollyky · 2022 to 2026
$815k
NHLBI NIH HHS R01 HL148184NIAID 75N93021F00003 (A-57)NIAID NIH HHS HHSN272201300020INIAID NIH HHS K24 AI166718NIAID NIH HHS R01 AI182349NIAID NIH HHS T32 AI007502NIDCD NIH HHS R01 DC019965NIGMS NIH HHS T32 GM007365NIGMS NIH HHS T32 GM139791
6 · The paper itself

Abstract

With the increasing prevalence of antimicrobial-resistant bacterial infections, there is interest in using bacteriophages (phages) to treat such infections. However, the factors that govern bacteriophage pharmacokinetics in vivo remain poorly understood. Here, we have examined the contribution of neutrophils, the most abundant phagocytes in the body, to the pharmacokinetics of i.v. administered bacteriophage in uninfected mice. A single dose of LPS-5, a bacteriophage recently used in human clinical trials to treat drug-resistant Pseudomonas aeruginosa, was administered i.v. to both immunocompetent BALB/c and neutropenic CD1 mice. Phage concentrations were assessed in peripheral blood and spleen at 0.25, 1, 2, 4, 8, 12, and 24 hours after administration by plaque assay and qPCR. We observed that the phage clearance was only minimally affected by neutropenia. Indeed, the half-lives of phages in blood in BALB/c and CD1 mice were 3.45 and 3.66 hours, respectively. These data suggest that neutrophil-mediated phagocytosis is not a major determinant of phage clearance. Conversely, we observed a substantial discrepancy in circulating phage levels over time when measured by qPCR versus plaque assay, suggesting that significant inactivation of circulating phages occurs over time. These data indicate that alternative factors, but not neutrophils, inactivate i.v. administered phages.

Indexed as

Mice, Inbred BALB CNeutrophilsPseudomonas aeruginosaPseudomonas InfectionsAnimalsBacteriophagesFemaleMiceNeutropeniaPhage TherapyPhagocytosisPseudomonas PhagesSpleenBacterial infectionsInfectious disease

Identifiers

PMID39435664
PMCPMC11530120

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Registered trials

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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.