ArticleThe Journal of antimicrobial chemotherapy2024
Differential in vitro susceptibility to ampicillin/ceftriaxone combination therapy among Enterococcus faecalis infective endocarditis clinical isolates.
Article in The Journal of antimicrobial chemotherapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Loss of Fsr quorum sensing promotes biofilm formation and worsens outcomes in enterococcal infective endocarditis.Nature communications · 2026Article
- Dual β-lactam synergy in Enterococcus faecalis and its relationship with penicillin-ceftriaxone infective endocarditis treatment outcomes.The Journal of antimicrobial chemotherapy · 2025Article
- Functional Genomics of Antibiotic Susceptibility in Enterococcus faecalis From Infective Endocarditis.The Journal of infectious diseases · 2025Article
- Therapeutic approach to difficult-to-treat multidrug-resistant enterococcal infections.Antimicrobial agents and chemotherapy · 2025Review
- Comparison of ceftriaxone versus ceftaroline in combination with ampicillin or penicillin againstMicrobiology spectrum · 2025Article
- High-Dose Ceftriaxone in Elderly Patients with Enterococcal Infective Endocarditis: Population Pharmacokinetics of Free Ceftriaxone and Dose Optimization.Antibiotics (Basel, Switzerland) · 2025Article
- Evaluation of ampicillin plus ceftobiprole combination therapy in treating Enterococcus faecalis infective endocarditis and bloodstream infection.Scientific reports · 2025Article
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
objectivesTo investigate the genomic diversity and β-lactam susceptibilities of Enterococcus faecalis collected from patients with infective endocarditis (IE).
methodsWe collected 60 contemporary E. faecalis isolates from definite or probable IE cases identified between 2018 and 2021 at the University of Pittsburgh Medical Center. We used whole-genome sequencing to study bacterial genomic diversity and employed antibiotic checkerboard assays and a one-compartment pharmacokinetic-pharmacodynamic (PK/PD) model to investigate bacterial susceptibility to ampicillin and ceftriaxone both alone and in combination.
resultsGenetically diverse E. faecalis were collected, however, isolates belonging to two STs, ST6 and ST179, were collected from 21/60 (35%) IE patients. All ST6 isolates encoded a previously described mutation upstream of penicillin-binding protein 4 (pbp4) that is associated with pbp4 overexpression. ST6 isolates had higher ceftriaxone MICs and higher fractional inhibitory concentration index values for ampicillin and ceftriaxone (AC) compared to other isolates, suggesting diminished in vitro AC synergy against this lineage. Introduction of the pbp4 upstream mutation found among ST6 isolates caused increased ceftriaxone resistance in a laboratory E. faecalis isolate. PK/PD testing showed that a representative ST6 isolate exhibited attenuated efficacy of AC combination therapy at humanized antibiotic exposures.
conclusionsWe find evidence for diminished in vitro AC activity among a subset of E. faecalis IE isolates with increased pbp4 expression. These findings suggest that alternate antibiotic combinations against diverse contemporary E. faecalis IE isolates should be evaluated.
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