Secondary hemophagocytic lymphohistiocytosis complicating culture-confirmed ceftriaxone-resistant Salmonella typhi infection: A rare case report

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome resulting from excessive immune activation. Although viruses are the most common infectious triggers of secondary HLH, Salmonella enterica serovar Typhi (S. Typhi) is an uncommon trigger, and the resulting syndrome may be mistaken for severe enteric fever. We describe a previously healthy 27-year-old Bangladeshi man who presented with prolonged high-grade fever, jaundice, diarrhoea, hepatosplenomegaly, ascites and progressive cytopenias. Blood culture grew a ceftriaxone- and ciprofloxacin-resistant S. Typhi that was also resistant to cefixime and ampicillin and susceptible to ertapenem and trimethoprim-sulfamethoxazole. Further evaluation showed marked hyperferritinaemia (24,658 ng/mL), hypertriglyceridaemia (567 mg/dL) and bone-marrow haemophagocytosis. The patient fulfilled six of the eight HLH-2004 criteria and had an HScore of 279 (estimated probability of HLH >99%). Screening for other endemic infections was negative, so S. Typhi was the only infectious trigger identified. Intravenous meropenem was started empirically on admission and continued after microbiological and clinical review because of third-generation cephalosporin resistance and severe systemic illness; ertapenem was the only carbapenem tested, so meropenem susceptibility was inferred rather than directly demonstrated. Intravenous dexamethasone was added for the hyperinflammatory response; the doses and durations of both drugs could not be retrieved from the medical records. After combined antimicrobial therapy and dexamethasone he became afebrile and his platelet count rose from 35 to 70 × 10⁹/L, but haemoglobin, bilirubin and albumin had not improved by the last documented inpatient tests, and laboratory values at discharge and follow-up were not available. He remained clinically well, with resolution of hepatosplenomegaly on ultrasonography, at follow-up in April 2026. Because both interventions were given during the same period, their individual contributions to recovery cannot be separated. This case highlights the need to consider HLH in patients with enteric fever who have persistent fever, worsening cytopenias, hepatosplenomegaly and marked hyperferritinaemia despite active antimicrobial therapy, and the value of combined infection-directed and immunomodulatory treatment.