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Published (Version of Record)CC BY-NC V4.0, Open Access
Journal article
Dual β-lactam synergy in Enterococcus faecalis and its relationship with penicillin-ceftriaxone infective endocarditis treatment outcomes
Journal of antimicrobial chemotherapy, dkaf377
2025
PMID: 41105431
Abstract
Objectives
Benzylpenicillin 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.
Methods
Clinical 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.
Results
Thirty-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.
Conclusions
Ceftriaxone 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.
Details
- Title
- Dual β-lactam synergy in Enterococcus faecalis and its relationship with penicillin-ceftriaxone infective endocarditis treatment outcomes
- Authors/Creators
- April Gregson - Concord Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, AustraliaShakeel Mowlaboccus - Murdoch UniversitySruthi Mamoottil Sudeep - Murdoch UniversitySophia Rizzo - Concord Repatriation General HospitalJignasa Purani - Westmead HospitalElena Martinez - The University of SydneyGeoffrey Coombs - Murdoch UniversityIndy Sandaradura - Westmead HospitalGenevieve McKew - Concord Repatriation General Hospital
- Publication Details
- Journal of antimicrobial chemotherapy, dkaf377
- Publisher
- Oxford University Press
- Number of pages
- 10
- Grant note
- Department of Infectious Diseases and Microbiology, Concord Hospital School of Medical, Molecular and Forensic Sciences, Murdoch University ioMérieux Australia
- Identifiers
- 991005823096507891
- Copyright
- © The Author(s) 2025.
- Murdoch Affiliation
- Centre for Biosecurity and One Health; School of Medical, Molecular and Forensic Sciences
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.23 Antibiotics & Antimicrobials
- 1.23.1442 Infective Endocarditis
- Web Of Science research areas
- Infectious Diseases
- Microbiology
- Pharmacology & Pharmacy
- ESI research areas
- Pharmacology & Toxicology