Evidence map›Paper›PMID 41105431›Full record

ArticleThe Journal of antimicrobial chemotherapy2025

Dual β-lactam synergy in Enterococcus faecalis and its relationship with penicillin-ceftriaxone infective endocarditis treatment outcomes.

April Gregson, Shakeel Mowlaboccus, Sruthi Mamoottil Sudeep, Sophia Rizzo, Jignasa Purani, Elena Martinez, Geoffrey Coombs, Indy Sandaradura, Genevieve McKew

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

9 authors.

April GregsonConcord Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
Shakeel MowlaboccusSchool of Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, WA, Australia.
Sruthi Mamoottil SudeepSchool of Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, WA, Australia.
Sophia RizzoConcord Microbiology, Concord Repatriation and General Hospital, NSW Health Pathology, Sydney, NSW, Australia.
Jignasa PuraniAntimicrobial Resistance Laboratory, Centre for Infectious Diseases and Microbiology, Institute for Clinical and Pathological Sciences, Westmead Hospital, NSW Health Pathology, Sydney, NSW, Australia.
Elena MartinezSchool of Medical Sciences, Faculty of Medicine and Sciences, University of Sydney, Sydney, NSW, Australia.
Geoffrey CoombsSchool of Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, WA, Australia.
Indy SandaraduraAntimicrobial Resistance Laboratory, Centre for Infectious Diseases and Microbiology, Institute for Clinical and Pathological Sciences, Westmead Hospital, NSW Health Pathology, Sydney, NSW, Australia.ORCID 0000-0002-9457-8262
Genevieve McKewConcord Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.ORCID 0000-0002-5238-9260

Funding

Department of Infectious Diseases and Microbiology, Concord HospitalioMérieux AustraliaSchool of Medical, Molecular and Forensic Sciences, Murdoch University
6 · The paper itself

Abstract

objectivesBenzylpenicillin with ceftriaxone is used for outpatient antimicrobial therapy of Enterococcus faecalis infective endocarditis (EFIE) due to poor stability of aminopenicillins. The aim was to correlate the impact of benzylpenicillin-ceftriaxone synergy on EFIE treated with benzylpenicillin-ceftriaxone, and investigate whether simpler phenotypic methods can predict synergy.

methodsClinical outcomes of a retrospective cohort of EFIE patients were correlated with treatment and synergy. Isolates were assessed for synergy using the checkerboard method, compared with double disc diffusion (DDD) and layered and crossed gradient diffusion strip (GDS) tests, with sensitivity and specificity of these methods calculated.

resultsThirty-eight episodes of EFIE in 34 patients were included; the majority received benzylpenicillin-ceftriaxone alone (n = 16) or in sequence (n = 12; any benzylpenicillin-ceftriaxone n = 28), and 10 received other regimens. There was no statistical difference between any benzylpenicillin-ceftriaxone versus other therapies on outcomes, nor between benzylpenicillin-ceftriaxone synergy and outcome. GDS was an unreliable predictor of checkerboard synergy; DDD was reasonable. Five isolates lacked benzylpenicillin-ceftriaxone synergy (one also lacking ampicillin-ceftriaxone synergy); these all had high-level ceftriaxone resistance [zone diameter 6 mm, or broth microdilution (BMD) MIC >512 mg/L]. Most isolates from relapse cases developed reduced zone diameters to ceftriaxone. Two isolates lacking synergy had the same mutation near the ceftriaxone response regulator (CroR) binding site in the pbp4 promoter region.

conclusionsCeftriaxone susceptibility, either MIC <512 mg/L by BMD or disc zone diameter >6 mm, is the best predictor of ampicillin-ceftriaxone and particularly benzylpenicillin-ceftriaxone synergy in E. faecalis. There was no clear relationship between the absence of benzylpenicillin-ceftriaxone synergy and outcome in this highly comorbid cohort.

Indexed as

Anti-Bacterial Agentsbeta-LactamsCeftriaxoneDrug SynergismEndocarditis, BacterialEnterococcus faecalisGram-Positive Bacterial InfectionsAdultAgedAged, 80 and overFemaleHumansMaleMicrobial Sensitivity TestsMiddle AgedRetrospective StudiesAnti-Bacterial Agentsbeta-LactamsCeftriaxone

Identifiers

PMID41105431
PMCPMC12670148

What OpenQuestion holds

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LicenceCC BY-NC
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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.