Does Ceftriaxone Cause Neutropenia? A Pharmacological Review

October 12, 2025 •

2 min read

The overall incidence of non-chemotherapy drug-induced neutropenia is between 2.4 and 15.4 cases per million people annually, with beta-lactam antibiotics like ceftriaxone being frequently implicated. So, does ceftriaxone cause neutropenia? Yes, it is a known, though rare, adverse effect.

Quick Summary

Ceftriaxone, a widely used antibiotic, can lead to neutropenia, a condition of low neutrophil white blood cells. This effect is rare but requires clinical awareness, especially with prolonged, high-dose therapy. Prompt discontinuation is key to management.

Key Points

Affirmative Link: Yes, ceftriaxone, a beta-lactam antibiotic, is known to cause neutropenia, though it is a rare adverse event.
Primary Risk Factors: The risk of developing neutropenia from ceftriaxone increases with prolonged duration of therapy (often beyond two weeks) and high cumulative doses.
Proposed Mechanisms: The condition is believed to result from either an immune-mediated destruction of neutrophils or direct toxic effects on bone marrow precursor cells.
Clinical Management: The cornerstone of management is the immediate discontinuation of ceftriaxone. Supportive care, including alternative antibiotics and potentially G-CSF, is crucial for recovery.
Prognosis: Recovery is common, with neutrophil counts typically returning to normal within 1 to 3 weeks after stopping the drug. Mortality is rare but can occur in severe cases.
Monitoring is Key: Due to the delayed onset, regular monitoring of blood counts is recommended for patients receiving long-term ceftriaxone treatment.
Relative Risk: Compared to other antibiotics, the risk with ceftriaxone is considered lower than with vancomycin but higher than some other beta-lactams.

Understanding the Link: Does Ceftriaxone Cause Neutropenia?

Ceftriaxone is a third-generation cephalosporin antibiotic used for various bacterial infections. A rare but significant side effect is drug-induced neutropenia, a reduction in absolute neutrophil count (ANC) below 1,500 cells/μL, which are vital for fighting infections. Severe neutropenia, or agranulocytosis, is defined as an ANC below 500 cells/μL.

Beta-lactam antibiotics, including ceftriaxone, are often linked to idiosyncratic drug-induced neutropenia, which has a low annual incidence. Clinical vigilance is important as neutropenia increases the risk of serious infections.

Mechanisms of Ceftriaxone-Induced Neutropenia

While the exact cause is unclear, two main mechanisms are proposed:

Immune-Mediated Destruction: The drug may trigger an immune response, leading to antibodies that destroy neutrophils.
Direct Myeloid Toxicity: Ceftriaxone might directly harm bone marrow cells that produce neutrophils, reducing their production. This can be dose-dependent.

Risk Factors and Onset

The risk of neutropenia is higher with longer treatment duration and cumulative dose.

Prolonged Therapy: Neutropenia often appears after about 21 days of treatment, but can vary.
High Cumulative Dose: Higher total doses increase the risk.
Other Factors: Age over 65, kidney issues, and severe sepsis can worsen outcomes.

Onset is typically delayed, emphasizing the need for monitoring during extended treatment. Some patients may also develop a rash or eosinophilia.

Comparison with Other Antibiotics

Neutropenia can occur with various antibiotics. Here's a comparison of risk:


Antibiotic Class	Examples	Relative Risk of Neutropenia	Notes
Cephalosporins	Ceftriaxone, Ceftaroline, Cefepime	Low to Moderate	Ceftaroline may have a higher risk than ceftriaxone.
Glycopeptides	Vancomycin	Moderate to High	Vancomycin is a common cause of antibiotic-induced neutropenia, with a higher incidence than ceftriaxone.
Penicillins	Cloxacillin, Piperacillin-tazobactam	Low to Moderate	Beta-lactams are frequently implicated in drug-induced neutropenia.
Carbapenems	Meropenem	Low	Meropenem-associated neutropenia is rare, particularly in adults.

Clinical Presentation and Management

Ceftriaxone-induced neutropenia can be asymptomatic or cause infection-related symptoms:

Fever and chills
Sore throat
Muscle and joint pain
Malaise

Managing suspected neutropenia involves:

Immediate Discontinuation: Stop ceftriaxone at once.
Supportive Care: Treat fever or infection with appropriate antibiotics.
Monitoring: Track ANC daily.
G-CSF Administration: Consider G-CSF for severe or prolonged cases to speed up recovery.

Neutrophil counts usually recover within 1-3 weeks after stopping the drug. The prognosis is generally good, though mortality is rare (2.5-5%) and more likely in elderly or critically ill patients.

Conclusion

In conclusion, does ceftriaxone cause neutropenia? Yes, it is a recognized, although uncommon, adverse effect. The risk rises with extended treatment and higher doses, likely due to immune or toxic mechanisms. Monitoring blood counts is advised for patients receiving long-term ceftriaxone. Prompt identification, discontinuation, and supportive care are crucial for patient safety and preventing severe infections.

For more information, see: Ceftriaxone-Induced Neutropenia in a Patient With a Brain Abscess

Frequently Asked Questions

Ceftriaxone-induced neutropenia is considered a rare adverse effect. The overall incidence of non-chemotherapy drug-induced neutropenia is 2.4-15.4 cases per million people annually, and ceftriaxone is one of several antibiotics implicated.

Neutropenia from ceftriaxone typically has a delayed onset, often appearing after prolonged treatment. The mean treatment duration before onset is about 21 days, but it has been reported to occur anywhere from 8 to more than 25 days into therapy.

Patients may be asymptomatic, or they may present with symptoms of an infection, such as fever, chills, sore throat, and muscle pain. A skin rash or eosinophilia can also occur concurrently.

The primary treatment is to immediately stop the ceftriaxone. If severe, treatment may also include supportive care, alternative antibiotics for any infection, and the administration of Granulocyte-Colony Stimulating Factor (G-CSF) to accelerate neutrophil recovery.

Neutrophil counts usually recover within one to three weeks after discontinuing ceftriaxone. Using G-CSF can shorten this recovery time.

Yes, patients on prolonged courses of ceftriaxone and those receiving high cumulative doses are at the greatest risk. Other general risk factors for poor outcomes from drug-induced neutropenia include being over 65 and having pre-existing renal failure.

There is a potential for cross-reactivity between beta-lactam antibiotics. However, some reports show that patients have been safely treated with an alternative beta-lactam with a different chemical structure. This decision must be made carefully by a clinician, often with close monitoring.