Clinical Outcomes and Safety Associated with Adjunctive Antibiotic-Loaded Calcium Sulphate Beads in Hip and Knee Periprosthetic Joint Infection: A Systematic Review

Background/Objectives: Antibiotic-loaded calcium sulphate beads (CSBs) are biodegradable local antibiotic carriers used as an adjunct to surgical and systemic antimicrobial treatment of periprosthetic joint infection (PJI). Their incremental clinical benefit, however, remains uncertain. This systematic review aimed to evaluate the effectiveness and safety of adjunctive antibiotic-loaded CSB in hip and knee PJI, with particular attention to outcomes according to surgical strategy. Methods: Five electronic databases (PubMed, Scopus, Web of Science, EBSCO, and Google Scholar) were searched from inception to 15 May 2026. Comparative non-randomized studies were assessed using ROBINS-I and non-comparative studies using the Joanna Briggs Institute critical appraisal tool. Comparative outcomes were synthesized according to surgical strategy. Formal meta-analysis was not performed because of clinical and methodological heterogeneity; descriptive aggregated proportions were used only for selected safety outcomes. Results: Thirteen studies comprising 859 CSB-treated PJI patients were included, comprising six comparative non-randomized and seven non-comparative observational studies. Infection-control rates in revision-based cohorts ranged from 75.0% to 95.7%, whereas implant-retention cohorts reported more variable success, ranging from 52.0% to 88.0%. No directly comparative one-stage study was identified. Descriptive aggregated proportions for explicitly reported safety outcomes were 4.7% for wound drainage, 5.7% for hypercalcaemia, and 2.1% for heterotopic ossification. Comparative studies had moderate-to-serious risk of bias, while JBI appraisal identified variable methodological limitations among non-comparative studies. Conclusions: Available evidence is predominantly observational and does not establish an independent treatment effect attributable to CSB. Comparative DAIR studies have not demonstrated a consistent reduction in reinfection, while comparative evidence for revision strategies remains limited. The incremental clinical benefit of adjunctive CSB remains uncertain, and higher-quality comparative studies with standardized treatment protocols, outcome definitions, and longer follow-up are needed.