Rationale: piperacillin-tazobactam, a widely used broad-spectrum antibiotic, carries a risk of severe adverse reactions, including rare but life-threatening hemophagocytic lymphohistiocytosis (HLH). Elevated procalcitonin (PCT), typically indicative of bacterial infection, can mask this diagnosis, leading to delayed recognition and potentially fatal outcomes. This case underscores the diagnostic challenge of drug-induced HLH mimicking infection. Patient concerns: a 17-year-old female presented with community-acquired pneumonia (CAP) and severe iron deficiency anemia. Initial piperacillin-tazobactam therapy resolved her fever and respiratory symptoms. However, after 6 afebrile days, she developed recurrent high-grade fever (40.3°C), pancytopenia (WBC 1.81 × 10 9 /L, ANC 0.23 × 10 9 /L, Hb 80 g/L, platelets 74 × 10 9 /L), hepatitis (AST 338 U/L, ALT 221 U/L), and rising serum ferritin (609.3 ng/mL) and PCT (3.057 ng/mL). Diagnoses: comprehensive evaluation excluded new infections (bacterial, viral including EBV/CMV), malignancies, autoimmune disorders, and other HLH triggers. Bone marrow morphology revealed hemophagocytic cells. Based on HLH-2004 criteria, she fulfilled 5 diagnostic criteria: fever, ≥2 lineage cytopenias, hyperferritinemia, hemophagocytosis in bone marrow, and progressive splenomegaly. The temporal association with drug exposure and resolution upon withdrawal confirmed piperacillin-tazobactam-induced HLH. Interventions: piperacillin-tazobactam was immediately discontinued upon suspicion of drug reaction. Despite elevated PCT prompting initiation of imipenem-cilastatin, the patient’s fever resolved spontaneously carbapenem before administration, and liver enzymes began improving the next day. Outcomes: following piperacillin-tazobactam cessation, fever resolved permanently within hours. Cytopenias, liver dysfunction, elevated ferritin, and PCT normalized progressively without specific HLH-directed immunosuppressive therapy. The patient was discharged symptom-free. Normal complete blood counts were confirmed at outpatient follow-ups over 13 months. Lessons: piperacillin-tazobactam can induce HLH, a critical diagnosis requiring immediate drug withdrawal. Elevated PCT in this context is a significant diagnostic pitfall, misleadingly suggesting bacterial infection progression. Unexplained fever and cytopenia during piperacillin-tazobactam therapy – even with elevated PCT – should prompt urgent evaluation for drug-induced HLH. Discontinuation of the causative agent is paramount for recovery and may obviate the need for unnecessary antimicrobial escalation or immunosuppressive therapy.
Xia et al. (2025) studied this question.