Agranulocytosis after High Cumulative Doses of Ceftriaxone in Infective Endocarditis: A Rare but Serious Adverse Reaction

Abstract

Background: Agranulocytosis is a serious, life-threatening condition characterized by a severe reduction in the number of peripheral neutrophils (<0.5 × 10⁹/L). It is most commonly caused by chemotherapy drugs but can be induced by antibiotics. Ceftriaxone is a widely used and generally safe third generation antibiotic for conditions such as infective endocarditis. Ceftriaxone induced agranulocytosis is an extremely rare adverse reaction. Evidence suggests that this adverse reaction is dose dependent and typically occurs following prolonged courses or high cumulative doses of the antibiotic. Despite improvements in management that reduce the mortality rate to approximately 5%, prompt recognition and treatment remain vital.
Case Presentation: A 56-year-old man diagnosed with native valve infective endocarditis (Streptococcus mitis) was treated with 2 g/day of intravenous ceftriaxone. In the fifth week of treatment, after receiving a cumulative dose of 60 g, the patient developed severe agranulocytosis, reaching a neutrophil nadir of 0.1 × 10⁹/L. Ceftriaxone was promptly stopped and replaced with teicoplanin, and the patient received filgrastim (recombinant human granulocyte colony stimulating factor [rhG CSF]). The case was classified as a probable adverse drug reaction (Naranjo score, 6). Neutrophil recovery was complete by the seventh day, and the patient successfully underwent double valve replacement surgery.
Conclusion: Ceftriaxone induced agranulocytosis, albeit rare, is a potentially fatal complication of prolonged therapy. Regular complete blood count monitoring and prompt management—based on drug withdrawal, appropriate antimicrobial coverage, and rhG CSF administration—are essential for favorable outcomes.