Antimicrobial elution from calcium sulfate beads: A systematic review of in vitro studies

Local antimicrobial delivery represents a fundamental adjunctive strategy in the management of osteoarticular and periprosthetic infections. Calcium sulfate beads (CSB) have gained increasing interest as biodegradable carriers capable of achieving high local antibiotic concentrations with minimal systemic exposure. However, reported in vitro elution profiles are highly variable, and no comprehensive systematic synthesis of the available experimental evidence currently exists. A systematic review was conducted in accordance with PRISMA 2020 guidelines, with a protocol previously registered in the Open Science Framework. Searches were performed in PubMed/MEDLINE, Scopus, and Web of Science from database inception to December 1, 2024. In vitro studies evaluating antimicrobial elution from calcium sulfate beads using quantitative or semi-quantitative longitudinal methods were included. Data extraction included elution kinetics, antimicrobial agents, bead characteristics, experimental conditions, and quantification methods. Methodological quality and risk of bias were assessed using a tool specifically adapted for in vitro elution studies. Twelve in vitro studies published between 2011 and 2023 were included, evaluating fourteen antimicrobial agents, predominantly vancomycin and tobramycin. Elution profiles consistently demonstrated a biphasic pattern, characterized by a high initial peak followed by a prolonged phase of decreasing release. Vancomycin maintained detectable levels for up to 3–6 weeks, whereas aminoglycosides showed higher early peaks with more rapid decline. Bead size, antibiotic formulation, drug combinations, elution medium, and experimental conditions significantly influenced elution kinetics. Most studies exhibited a moderate methodological risk of bias. In vitro evidence supports calcium sulfate as a versatile carrier for local antimicrobial delivery; however, marked methodological heterogeneity limits quantitative comparability and clinical extrapolation. Standardized in vitro protocols and translational studies are required to optimize its clinical application.