From suspected necrotizing fasciitis to diagnosed drug-induced fever: a diagnostic maze and reflections on anti-infection management in a case of postoperative fever after femoral fracture.

Postoperative fever represents a common clinical challenge in orthopedics, and the differential diagnosis of its etiology directly influences anti-infective decision-making and patient outcomes. In the context of anti-infective therapy, "drug fever" induced by antimicrobial agents themselves can easily be mistaken for uncontrolled or recurrent infection, leading to antibiotic overuse. This article reports the case of a 49-year-old male with a comminuted fracture of the right femur. Preoperatively, he presented with post-traumatic absorption fever. Postoperatively, due to intraoperative observation of fascial necrosis and a sharp rise in inflammatory markers, a high clinical suspicion of necrotizing fasciitis prompted the initiation of triple broad-spectrum antibiotic therapy (clindamycin + piperacillin-tazobactam + vancomycin). After initial infection control, a regular afternoon high-grade fever emerged in the second postoperative week, accompanied by a "vancomycin infusion syndrome"-like rash and agranulocytosis. Through systematic exclusion of infectious sources and a rigorous drug withdrawal trial, the final diagnosis was confirmed as "antimicrobial-associated drug fever." This case comprehensively illustrates the three-stage dynamic evolution of perioperative fever: from "traumatic inflammation" to "bacterial infection" and finally to "drug fever." It highlights that clinicians should maintain high vigilance during active anti-infective treatment for the sequential phenomenon whereby "the therapeutic agents themselves become a new source of fever after infection control," in order to avoid inappropriate prolongation of antibiotics due to misjudgment and to reinforce the principles of antimicrobial stewardship.