Antimicrobials in Cement: A Modern Summary of What Has Been Used and What Can Be Used

Background: Bone, joint, and soft tissue infections are problems that orthopedic surgeons frequently encounter. Antibiotic-loaded bone cement (ALBC) provides an option to deliver high, local concentrations of antimicrobials to treat infections. However, there are many factors that need to be considered when choosing the ideal antimicrobial to incorporate into ALBC. This systematic review aims to provide a modern summary of antimicrobials that have been used in ALBC, characterize the antimicrobial agents incorporated into orthopedic polymethyl methacrylate (PMMA) bone cement, summarize their physicochemical and antimicrobial properties, identify the pathogens they target, and review their reported clinical applications. Methods: Following PRISMA guidelines, a systematic search of Scopus, Google Scholar, Embase, and PubMed was conducted using search terms encompassing ALBC, biomechanical properties, elution properties, antimicrobial activity, delivery, and stability. Results: The search yielded 562 database records and 19 from citation searching. After screening, 105 studies published between 2010 and 2026 were included, comprising 58.1% in vitro and 41.9% clinical studies. Thirty-five unique antimicrobial agents were identified, most commonly aminoglycosides and glycopeptides. Other antimicrobials were antifungal, antimycobacterial, and broad-spectrum agents. Antimicrobial elution generally followed a burst release within 24–72 h followed by declining sustained release, with duration varying from a few days to detectable levels beyond 30 days. Antimicrobial activity and elution were dose-dependent, and certain combinations enhanced elution or antibacterial activity. Increasing antimicrobial dose consistently reduced cement mechanical strength, though most formulations remained above International Organization for Standardization (ISO) minimums. Preparation method and formulation further influenced elution and mechanical performance. Reported clinical eradication rates were high but heterogeneous and frequently confounded by concurrent debridement and systemic therapy. Conclusions: A broad and expanding range of antimicrobials has been incorporated into bone cement for orthopedic infection, extending beyond traditional aminoglycoside and glycopeptide formulations. Antimicrobial selection involves balancing elution, antimicrobial spectrum, thermal stability, and mechanical integrity. Current evidence is dominated by heterogeneous in vitro studies and confounded clinical series, highlighting the need for standardized investigation, particularly of less commonly used agents.