A Severe Case of Drug Reaction with Eosinophilia and Systemic Symptoms After Sequential Cephalosporin and Vancomycin Exposure

Aims: To describe a severe case of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) associated with sequential cephalosporin and vancomycin exposure, and to highlight the diagnostic challenges and hematologic and thromboembolic complications encountered during the clinical course. Place and Duration of Study: Central Maine Medical Center, Lewiston, Maine, USA; September 2025 to November 2025. Methodology: Clinical data were obtained through detailed review of the patient’s medical records, including medication timeline, laboratory trends, imaging studies, histopathology reports, and clinical response to therapeutic interventions. Serial eosinophil percentages and absolute neutrophil counts were analyzed in relation to antibiotic exposure and treatment milestones. Diagnostic probability was assessed using the RegiSCAR scoring system, and drug causality was evaluated using the World Health Organization–Uppsala Monitoring Centre (WHO–UMC) causality assessment method. Results: A 45-year-old woman with transfusion-dependent chronic anemia, cognitive delay, and chronic kidney disease developed a progressive morbilliform rash, facial edema, marked eosinophilia, and profound neutropenia following prolonged exposure to intravenous ceftriaxone and oral cefdinir for a complicated urinary tract infection secondary to an obstructive renal stone. Brief exposure to vancomycin was followed by rapid clinical worsening, raising concern for immunologic amplification of an evolving hypersensitivity reaction. Her course was further complicated by acute deep vein thrombosis and pulmonary embolism. Skin biopsy demonstrated findings consistent with a drug-induced hypersensitivity reaction. Initiation of systemic corticosteroids resulted in rapid improvement in both cutaneous and hematologic abnormalities. Discussion: This case underscores the importance of early recognition of DRESS in patients receiving sequential antibiotic therapy. The clinical timeline supports cephalosporins as the likely primary sensitizing agents, with vancomycin acting as a potential immunologic accelerator. Concurrent exposure to two cell wall synthesis inhibitors may also have contributed to immune activation in this case. Both cephalosporins and vancomycin target bacterial cell wall formation but are independently associated with severe delayed hypersensitivity reactions. Sequential exposure may increase antigenic stimulation and immune dysregulation in susceptible individuals, potentially contributing to clinical severity. Prompt initiation of systemic corticosteroids may be critical in reversing severe hematologic and systemic complications.