Systemic absorption and nephrotoxicity of antibiotic-loaded cement spacers: pharmacokinetic principles and clinical risk management

Antibiotic-loaded polymethylmethacrylate (PMMA) spacers are widely used during staged revision for periprosthetic joint infection (PJI) to provide high local antimicrobial exposure, but they are not pharmacologically isolated from the systemic circulation. Human pharmacokinetic studies demonstrate measurable vancomycin and aminoglycoside concentrations after implantation, sometimes persisting for weeks, while clinical studies report heterogeneous rates of acute kidney injury (AKI) across populations and spacer regimens. Risk cannot be inferred from grams of antibiotic per 40 g of cement alone: formulation concentration, total implanted drug mass, cement mass, release kinetics, spacer geometry, concurrent systemic therapy, perioperative hemodynamics, and patient-specific renal clearance are related but distinct determinants of systemic exposure. This Mini Review integrates PMMA elution principles with quantitative human evidence, separates evidence of spacer-derived absorption from associations with AKI and from general perioperative risk factors, and proposes a pragmatic risk-management framework. The framework is not prospectively validated. Safer use requires stable-baseline renal risk assessment, explicit documentation of total antibiotic and cement doses, coordinated local and systemic prescribing, early monitoring in high-risk inpatients, selective serum drug measurement when exposure or toxicity is suspected, and multidisciplinary escalation for persistent toxicity. Future studies should use standardized dose, sampling, exposure, and KDIGO-defined renal outcome metrics and should distinguish spacer-derived from intravenously administered drug exposure.