{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:17:20Z","timestamp":1790828240132,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["140388\/2022-2"],"award-info":[{"award-number":["140388\/2022-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Cutibacterium acnes is increasingly recognized as a relevant pathogen in orthopaedic implant-associated infections, yet treatment strategies remain largely empirical. With rising antimicrobial resistance and scarce data on drug interactions, optimizing targeted therapies is essential. This preclinical study investigated the efficacy and synergism of vancomycin (VA), gentamicin (GEN), and ceftriaxone (CTX) against two clinical phylotype IB strains from orthopaedic infections and the reference strain C. acnes ATCC 6919, using both in vitro and in vivo models. Methods: Minimum inhibitory concentrations (MICs) were determined using broth microdilution following BrCAST guidelines. Synergistic activity was assessed using the checkerboard assay and interpreted via fractional inhibitory concentration indices (FICIs). The in vivo efficacy of antibiotic combinations with bioactive glass S53P4 (BAG) was evaluated in the Galleria mellonella infection model. Results: All C. acnes strains exhibited uniformly low MICs. Synergistic activity was observed for CTX combined with GEN in strain 2 (FICI range 0.25\u20130.37), while partial synergy was detected for CTX with GEN in strain 1 (FICI \u2248 0.56\u20130.63), and for CTX combined with VA in the ATCC strain (FICI = 0.66). All other combinations demonstrated indifferent interactions. In the G. mellonella model, a high bacterial inoculum (OD600 of 3.0) was needed to establish an infection. For all strains tested, the use of antibiotics in combination with BAG improved larval survival. For the clinical strains, the combination of CTX + GEN + BAG and BAG alone demonstrated greater efficacy in promoting larval survival. Conclusions: Acombination of a cephalosporin with an aminoglycoside, particularly when incorporated into a biomaterial matrix, enhances antimicrobial activity against both clinical and reference strains of C. acnes.<\/jats:p>","DOI":"10.3390\/antibiotics14090923","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T12:34:03Z","timestamp":1757680443000},"page":"923","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synergistic Antimicrobial Activity of Vancomycin, Ceftriaxone, and Gentamicin Against Cutibacterium acnes Strains: An In Vitro Checkerboard Analysis and In Vivo Interaction with Bioactive Glass Using Galleria mellonella"],"prefix":"10.3390","volume":"14","author":[{"given":"Mariana Neri Lucas","family":"Kurihara","sequence":"first","affiliation":[{"name":"Special Laboratory of Clinical Microbiology (LEMC), Department of Medicine, Division of Infectious Diseases, Escola Paulista de Medicina (EPM), Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04024-002, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4899-1888","authenticated-orcid":false,"given":"Isabelle Frois","family":"Brasil","sequence":"additional","affiliation":[{"name":"Special Laboratory of Clinical Microbiology (LEMC), Department of Medicine, Division of Infectious Diseases, Escola Paulista de Medicina (EPM), Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04024-002, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayara Muniz de Andrade","family":"Silva","sequence":"additional","affiliation":[{"name":"Special Laboratory of Clinical Microbiology (LEMC), Department of Medicine, Division of Infectious Diseases, Escola Paulista de Medicina (EPM), Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04024-002, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5443-6024","authenticated-orcid":false,"given":"Mauro Jose","family":"Salles","sequence":"additional","affiliation":[{"name":"Special Laboratory of Clinical Microbiology (LEMC), Department of Medicine, Division of Infectious Diseases, Escola Paulista de Medicina (EPM), Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04024-002, Brazil"},{"name":"Musculoskeletal Infection Group, Department of Orthopedics and Traumatology, Escola Paulista de Medicina (EPM), Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04024-002, Brazil"},{"name":"Infectious Disease Discipline, Faculdade de Ci\u00eancias M\u00e9dicas da Santa Casa de S\u00e3o Paulo, S\u00e3o Paulo 01224-001, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Thoraval, L., Varin-Simon, J., Ohl, X., Velard, F., Reffuveille, F., and Tang-Fichaux, M. 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