Academic Journal
High and Sustained Release of the Novel Echinocandin Rezafungin From Bone Cement: An In Vitro Comparison With Liposomal Amphotericin B and Micafungin.
| Τίτλος: | High and Sustained Release of the Novel Echinocandin Rezafungin From Bone Cement: An In Vitro Comparison With Liposomal Amphotericin B and Micafungin. |
|---|---|
| Συγγραφείς: | Prats-Peinado L; Department of Orthopaedic Surgery and Traumatology, Hospital General Universitario Gregorio Marañón, Madrid, Spain., Peral Y; Faculty of Biology, Universidad Complutense de Madrid, Madrid, Spain., Díaz-Navarro M; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain., Márquez-Gómez M; Department of Orthopaedic Surgery and Traumatology, Hospital General Universitario Gregorio Marañón, Madrid, Spain., Vaquero-Martín J; Department of Orthopaedic Surgery and Traumatology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Medicine Department, School of Medicine, Universidad Complutense de Madrid, Spain., Muñoz P; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Medicine Department, School of Medicine, Universidad Complutense de Madrid, Spain; CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain., Guembe M; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain., Sanz-Ruíz P; Department of Orthopaedic Surgery and Traumatology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Faculty of Biology, Universidad Complutense de Madrid, Madrid, Spain; Medicine Department, School of Medicine, Universidad Complutense de Madrid, Spain. |
| Πηγή: | The Journal of arthroplasty [J Arthroplasty] 2026 Oct; Vol. 41 (10S1), pp. S445-S451.e1. Date of Electronic Publication: 2026 May 28. |
| Τύπος έκδοσης: | Journal Article; Comparative Study |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Taylor and Francis Country of Publication: United States NLM ID: 8703515 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-8406 (Electronic) Linking ISSN: 08835403 NLM ISO Abbreviation: J Arthroplasty Subsets: MEDLINE |
| Imprint Name(s): | Publication: New Brunswick, NJ : Taylor and Francis Original Publication: [New York, NY : Churchill Livingstone, c1986- |
| Ιατρικοί όροι (MeSH): | Antifungal Agents*/pharmacology , Antifungal Agents*/pharmacokinetics , Amphotericin B*/pharmacology , Amphotericin B*/pharmacokinetics , Echinocandins*/pharmacology , Echinocandins*/pharmacokinetics , Bone Cements*/chemistry , Lipopeptides*/pharmacology, Biofilms/drug effects ; Prosthesis-Related Infections/drug therapy ; Micafungin ; Delayed-Action Preparations ; Polymethyl Methacrylate ; Microbial Sensitivity Tests ; Humans |
| Περίληψη: | Background: Fungal periprosthetic joint infections are difficult-to-treat infections due to the complexity of fungal biofilm and to the limited number of antifungal agents that both elute effectively and remain active when incorporated into polymethylmethacrylate (PMMA) bone cement. Rezafungin (REZA), a next-generation, long-acting echinocandin with antibiofilm activity, may overcome these limitations. This study evaluated the in vitro elution kinetics of REZA from PMMA, assessed whether antibiofilm activity was maintained after elution, and compared its performance with micafungin (MICA) and gold standard liposomal amphotericin B (AmB). Methods: A commercial gentamicin-loaded bone cement was mixed with REZA or MICA at 0.5 and 1% and with AmB at 0.5%. Standardized samples (n = 3 per group) were incubated in phosphate-buffered saline under agitation. Eluates were collected at 10 time points from one hour to six weeks and quantified by liquid chromatography-mass spectrometry (AmB) or high-performance liquid chromatography (MICA and REZA). Cumulative drug release (area under the curve [AUC]) was calculated for each group. The antifungal activity of first-hour eluates of each drug was tested against 12 strains of Candida spp., using a 24-hour biofilm inhibition assay. Results: The REZA achieved the highest and most sustained elution, with 24-hour concentrations of 1,789 μg/mL (1%) and 1,738 μg/mL (0.5%), exceeding AmB 0.5% by greater than 150-fold. The AUC Conclusions: The REZA eluted from PMMA at high concentrations, releasing significantly more drug than MICA or AmB. Drug release was consistent with a concentration-dependent elution. All three antifungal agents retained metabolic activity, but REZA surpassed its MIC (C albicans) by more than 10,000-fold, a margin that may translate into enhanced antibiofilm activity. (Copyright © 2026 Elsevier Inc. All rights reserved.) |
| Contributed Indexing: | Keywords: amphotericin B; bone cement; elution; micafungin; periprosthetic joint infection; rezafungin |
| Substance Nomenclature: | R10H71BSWG (Micafungin) 0 (Antifungal Agents) 7XU7A7DROE (Amphotericin B) 0 (Echinocandins) 0 (liposomal amphotericin B) G013B5478J (Rezafungin) 0 (Bone Cements) 0 (Delayed-Action Preparations) 0 (Lipopeptides) 9011-14-7 (Polymethyl Methacrylate) |
| Entry Date(s): | Date Created: 20260528 Date Completed: 20260928 Latest Revision: 20260928 |
| Update Code: | 20260929 |
| DOI: | 10.1016/j.arth.2026.05.047 |
| PMID: | 42208696 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1532-8406 |
|---|---|
| DOI: | 10.1016/j.arth.2026.05.047 |