Drug Reaction with Eosinophilia and Systemic Symptoms Following Antibiotic Cement Spacer Placement

Case: A 44-year-old woman with an infected pilon fracture nonunion developed Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) after prolonged intravenous vancomycin and implantation of a vancomycin/tobramycin-loaded antibiotic cement spacer (ACS). Fevers, rash, and eosinophilia persisted despite stopping systemic vancomycin and starting corticosteroids. ACS explantation led to symptom resolution; however, severe thrombocytopenia developed, requiring therapeutic plasma exchange. A daptomycin-loaded spacer was reimplanted before definitive hindfoot fusion. Conclusion: This case of DRESS in the setting of an ACS highlights management challenges, supports early recognition and spacer removal, proposes a treatment algorithm, and suggests daptomycin as an alternative for local antibiotic delivery.