Beyond Vancomycin and Gentamicin: Alternative Antimicrobials for Local Delivery in Multidrug-Resistant Bone and Joint Infections Across Different Carrier Systems

Introduction & Aim Multidrug-resistant organisms (MDROs) account for a growing proportion of bone and joint infections, and classical local delivery of vancomycin and gentamicin/tobramycin no longer reliably covers the full pathogen spectrum — in particular vancomycin-resistant enterococci (VRE), extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales, non-fermenting Gram-negatives and fungi. Evidence on alternative antimicrobials remains dispersed and difficult to apply at the bedside. We mapped in vitro and clinical evidence on alternative antimicrobials for local delivery through the three carrier families commonly used — polymethylmethacrylate (PMMA), calcium sulfate and antibacterial hydrogel coatings — to produce an antimicrobial-by-carrier reference to guide carrier choice when facing an MDRO. Methods A scoping review was conducted in PubMed, Scopus and Web of Science (1964–2025) for studies on local delivery of ceftaroline, daptomycin, linezolid, tigecycline, rifampicin, amikacin, colistin, meropenem and selected antifungals (amphotericin B deoxycholate and liposomal, caspofungin, fluconazole, posaconazole, voriconazole) in PMMA, calcium sulfate and hydrogel carriers. Manufacturer-supplied unpublished data were treated as hypothesis-generating. The 57 included studies were synthesised by carrier and antimicrobial. Results Evidence was dominated by in vitro elution studies, complemented by case reports and small single-centre series; no randomised data were identified. In PMMA, daptomycin (1–3 g/40 g), linezolid (1–1.2 g/40 g) and tigecycline (1 g/40 g) preserved ISO 5833 mechanical standards and achieved elution above the minimum inhibitory concentration (MIC) for target Gram-positive pathogens; meropenem, amikacin and colistin showed adequate short-term elution, with clinical feasibility supported only by case reports and small series. Calcium sulfate offered broader compatibility —including tigecycline, colistin and most antifungals — with higher early elution but shorter supra-MIC windows (typically 24–96 h). Hydrogel coatings allowed delivery of daptomycin, meropenem and antifungals with near-complete elution within 96 h. Dual-antibiotic combinations frequently improved elution through passive opportunism, requiring case-by-case balance against cytotoxicity and mechanical compromise. Conclusions A wide range of alternative antimicrobials is compatible with at least one carrier, providing pragmatic options when vancomycin and gentamicin/tobramycin are inadequate. Carrier choice is scenario-driven: PMMA for weight-bearing sustained release; calcium sulfate for adjunctive dead-space management; hydrogel for early-window protection. The evidence base remains predominantly in vitro, with narrow carrier-dependent supra-MIC windows and no high-level clinical data, precluding formal dose recommendations. The proposed antimicrobial-by-carrier table is a bedside reference, not a guideline.