Evidence map›Paper›PMID 35472061›Full record

ArticlePloS one2022

Efficacy assessment of a novel endolysin PlyAZ3aT for the treatment of ceftriaxone-resistant pneumococcal meningitis in an infant rat model.

Luca G Valente, Ngoc Dung Le, Melissa Pitton, Gabriele Chiffi, Denis Grandgirard, Stephan M Jakob, David R Cameron, Grégory Resch, Yok-Ai Que, Stephen L Leib

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 37% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Article
  3. Endolysins: targetingFrontiers in microbiology · 2025
    Review
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 1 institution in 1 country.

Luca G ValenteInstitute for Infectious Diseases, University of Bern, Bern, Switzerland.
Ngoc Dung LeInstitute for Infectious Diseases, University of Bern, Bern, Switzerland.
Melissa PittonDepartment of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Gabriele ChiffiInstitute for Infectious Diseases, University of Bern, Bern, Switzerland.
Denis GrandgirardInstitute for Infectious Diseases, University of Bern, Bern, Switzerland.ORCID 0000-0002-4151-5196
Stephan M JakobDepartment of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
David R CameronDepartment of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Grégory ReschCentre for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital, Lausanne, Switzerland.
Yok-Ai QueDepartment of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Stephen L LeibInstitute for Infectious Diseases, University of Bern, Bern, Switzerland.ORCID 0000-0002-1106-6123
University of Bern · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTreatment failure in pneumococcal meningitis due to antibiotic resistance is an increasing clinical challenge and alternatives to antibiotics warrant investigation. Phage-derived endolysins efficiently kill gram-positive bacteria including multi-drug resistant strains, making them attractive therapeutic candidates. The current study assessed the therapeutic potential of the novel endolysin PlyAZ3aT in an infant rat model of ceftriaxone-resistant pneumococcal meningitis.

methodsEfficacy of PlyAZ3aT was assessed in a randomized, blinded and controlled experimental study in infant Wistar rats. Meningitis was induced by intracisternal infection with 5 x 107 CFU/ml of a ceftriaxone-resistant clinical strain of S. pneumoniae, serotype 19A. Seventeen hours post infection (hpi), animals were randomized into 3 treatment groups and received either (i) placebo (phosphate buffered saline [PBS], n = 8), (ii) 50 mg/kg vancomycin (n = 10) or (iii) 400 mg/kg PlyAZ3aT (n = 8) via intraperitoneal injection. Treatments were repeated after 12 h. Survival at 42 hpi was the primary outcome; bacterial loads in cerebrospinal fluid (CSF) and blood were secondary outcomes. Additionally, pharmacokinetics of PlyAZ3aT in serum and CSF was assessed.

resultsPlyAZ3aT did not improve survival compared to PBS, while survival for vancomycin treated animals was 70% which is a significant improvement when compared to PBS or PlyAZ3aT (p<0.05 each). PlyAZ3aT was not able to control the infection, reflected by the inability to reduce bacterial loads in the CSF, whereas Vancomycin sterilized the CSF and within 25 h. Pharmacokinetic studies indicated that PlyAZ3aT did not cross the blood brain barrier (BBB). In support, PlyAZ3aT showed a peak concentration of 785 μg/ml in serum 2 h after intraperitoneal injection but could not be detected in CSF.

conclusionIn experimental pneumococcal meningitis, PlyAZ3aT failed to cure the infection due to an inability to reach the CSF. Optimization of the galenic formulation e.g. using liposomes might enable crossing of the BBB and improve treatment efficacy.

Indexed as

Meningitis, PneumococcalAnimalsAnti-Bacterial AgentsCeftriaxoneEndopeptidasesRandom AllocationRatsRats, WistarStreptococcus pneumoniaeVancomycinAnti-Bacterial AgentsCeftriaxoneendolysinEndopeptidasesVancomycin

Identifiers

PMID35472061
PMCPMC9041855
OpenAlexW4224699390

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.