| Title: |
Paradoxical interaction between dalbavancin and β-lactams against endocarditis-associated Enterococcus faecalis clinical isolates |
| Authors: |
Luque Paz, David; Turban, Adrien; Guérin, François; Penven, Malo; Revest, Matthieu; de La Maria, Cristina García; Miro, Jose, M; Tattevin, Pierre; Cattoir, Vincent |
| Contributors: |
ARN bactériens et médecine (BRM); Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes (Biosit : Biologie - Santé - Innovation Technologique); Centre Hospitalier Universitaire Rennes = Rennes University Hospital Pontchaillou; Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona (UAB); Instituto de Salud Carlos III Madrid (ISCIII); D.L.P. received the International Mobility Grant 2024 from the Réunion Interdisciplinaire de Chimiothérapie Anti-Infectieuse (RICAI), the Rennes University Hospital International Mobility Grant 2022, and the support of the Collège Doctoral de Bretagne Outgoing International Mobility Programme 2024 to fund his stay in the laboratory ‘Endocarditis. Cardiovascular infections. Experimental model’, Fundació Clínic per a la Recerca Biomèdica–Institut d’Investigacions Biomèdiques August Pi i Sunyer (FCRB/IDIBAPS), Hospital Clínic Barcelona, Spain (November 2024 to November 2025). J.M.M. received a personal 80:20 research grant from IDIBAPS, Barcelona, Spain, during 2017–25. We are very grateful to the institutions that supported this project, namely the French Society of Infectious Diseases (SPILF), the French Association of Antimicrobial Chemotherapy (ACAI), Rennes University Hospital and the Collège Doctoral de Bretagne. |
| Source: |
ISSN: 0305-7453. |
| Publisher Information: |
CCSD; Oxford University Press (OUP) |
| Publication Year: |
2025 |
| Collection: |
Inserm: HAL (Institut national de la santé et de la recherche médicale) |
| Subject Terms: |
Antibiotics; Enterococcus; Pharmacology; Vancomycin; Imipenem; Staphylococcus aureus; Antibiotic resistance; Dalbavancin; Enterococcus faecalis; Teicoplanin; Ertapenem; Cefepime; Meropenem; Bacteria; [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology |
| Description: |
International audience ; Background: There are limited in vitro synergistic studies on dalbavancin against enterococci. We aimed to assess the in vitro activity of dalbavancin against Enterococcus faecalis strains, and to explore the interaction between dalbavancin and β-lactams.Methods: MIC and MBC values were determined against a panel of 10 clinical isolates and two reference strains of E. faecalis. Checkerboard assays were conducted for the initial screening for additive, synergistic or antagonistic effect between dalbavancin and different classes of antibiotics. Thereafter, time-kill (TK) assays with β-lactams were performed to confirm the results.Results: All strains were tolerant to dalbavancin (MBC/MIC ratios >32). For 11 of the 12 strains tested, a synergy was found in TK assays between dalbavancin (0.5 × MIC) and each β-lactam (0.25 × MIC), namely amoxicillin, cefazolin, ceftriaxone, cefepime, ceftobiprole, ertapenem and meropenem. Paradoxically, we systematically found reduced efficacy of β-lactams in combination with dalbavancin at concentrations greater than or equal to MIC. At these concentrations, TK assays demonstrated that a combination with dalbavancin resulted in an antagonism of amoxicillin (8/12 strains), ceftobiprole (10/12 strains) and ertapenem (5/12 strains) activities. Dalbavancin alone at 32 mg/L or in combination with amoxicillin at 2 mg/L induced a slow bacterial reduction (median decrease of 0.4 log10 at 24 h for both regimens), whereas amoxicillin alone at 2 mg/L reduced the E. faecalis inoculum by 3.2 log10 (IQR, 3.1-3.4).Conclusions: Dalbavancin exhibits poor activity against E. faecalis, and impairs the activity of β-lactams, especially amoxicillin. Dalbavancin should be used with caution in the treatment of E. faecalis infective endocarditis. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/40720087; PUBMED: 40720087 |
| DOI: |
10.1093/jac/dkaf262 |
| Availability: |
https://hal.science/hal-05240655; https://hal.science/hal-05240655v1/document; https://hal.science/hal-05240655v1/file/Luque%20Paz%20-%202025%20-%20Paradoxical%20interaction%20between%20dalbavancin%20and%20%CE%B2-lactams%20against%20endocarditis-associated%20Enterococcus%20faecalis%20clinical%20isolates%20_R1_Manuscript_clean_version_pour%20HAL.pdf; https://doi.org/10.1093/jac/dkaf262 |
| Rights: |
https://creativecommons.org/licenses/by-nc/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.6FEEF13E |
| Database: |
BASE |