Can Ceftriaxone Cause Leukopenia?
Yes, ceftriaxone can cause leukopenia and neutropenia, though this is an uncommon adverse effect that typically occurs with prolonged therapy and is reversible upon discontinuation of the drug.
Mechanism and Evidence from FDA Labeling
The FDA-approved labeling for ceftriaxone explicitly warns about hematologic adverse effects. The drug label states that "an immune mediated hemolytic anemia has been observed in patients receiving cephalosporin class antibacterials including ceftriaxone" and notes that severe cases have been reported in both adults and children 1, 2. While the FDA label emphasizes hemolytic anemia more prominently, it also documents that thrombocytopenia with leukopenia has occurred during ceftriaxone therapy 3.
Clinical Evidence and Case Reports
Recent case reports confirm ceftriaxone-induced neutropenia as a documented adverse effect:
A 2024 case report documented neutropenia induced by both ceftriaxone and meropenem in an adult patient, with resolution occurring within 48 hours of discontinuation 4. This report emphasizes that while antibiotic-induced neutropenia is uncommon, it can lead to severe neutropenia, septicemia, and septic shock 4.
Historical data from 1983 documented a case where ceftriaxone administration was stopped due to thrombocytopenia with leukopenia, though the authors noted this could not be attributed exclusively to ceftriaxone 3.
Clinical Characteristics
Timing and Risk Factors
- Neutropenia associated with beta-lactam antibiotics like ceftriaxone is more likely with prolonged therapy (generally occurring at least 20 days after initiation) 5
- The adverse effect is considered idiosyncratic and life-threatening but extremely rare 4
Severity and Outcomes
- Can progress to severe neutropenia with potential for septicemia, septic shock, deep-seated infections, and death 4
- Mortality from antibiotic-induced neutropenia remains rare, ranging from 2.5-5% 4
- The condition is reversible with cessation of the offending agent 4
Management Recommendations
Monitoring
- For short courses of ceftriaxone (≤3 days), routine monitoring of complete blood counts is generally not necessary in patients with normal baseline values 6
- For prolonged therapy, monitoring of leukocytes and neutrophils is warranted 5
Treatment if Neutropenia Develops
- Immediately discontinue ceftriaxone 4
- Initiate neutropenic sepsis treatment without delay if the patient becomes septic and febrile 4
- Consider granulocyte-colony stimulating factor (G-CSF) to facilitate recovery with daily monitoring of neutrophil count 4
- Provide supportive treatment as needed 4
Common Pitfalls to Avoid
- Do not dismiss mild cytopenias during prolonged ceftriaxone therapy—early recognition is critical 4
- Do not delay treatment if neutropenic fever develops, as this can rapidly progress to life-threatening sepsis 4
- Do not assume other causes without considering drug-induced neutropenia in patients on ceftriaxone who develop low white counts 4