Can Ceftriaxone Cause Leukocytosis? Understanding an Uncommon Side Effect

October 12, 2025 •

4 min read

While commonly associated with treating infection, a notable but rare adverse effect of the antibiotic ceftriaxone is an increase in white blood cell (WBC) count. Although clinicians are typically more concerned with leukopenia (low WBCs), understanding that can ceftriaxone cause leukocytosis is important for accurate diagnosis and management.

Quick Summary

Ceftriaxone is known to cause various blood count changes. Though primarily associated with decreases in white blood cells (leukopenia), it has been reported to cause rare instances of leukocytosis, an elevated white blood cell count. This is often linked to hypersensitivity or allergic reactions and is distinct from the leukocytosis caused by the underlying infection being treated.

Key Points

Rare Side Effect: Leukocytosis is a rare adverse effect of ceftriaxone, with a reported incidence of less than 0.1%.
Commonly Causes Leukopenia: A decreased white blood cell count (leukopenia) and increased eosinophils (eosinophilia) are more common hematological changes.
Linked to Hypersensitivity: Drug-induced leukocytosis is often associated with immune-mediated or hypersensitivity reactions, as seen in cases of leukocytoclastic vasculitis.
Clinical Diagnosis Challenge: It is difficult to distinguish drug-induced leukocytosis from the normal inflammatory response to the infection being treated.
Resolution Upon Discontinuation: The elevated WBC count from a drug reaction should resolve within a few days to weeks after discontinuing ceftriaxone.
Important Context: The presence of other allergic symptoms, lack of a 'left shift', and improvement after stopping the drug are key to confirming drug-induced leukocytosis.

Ceftriaxone is a powerful third-generation cephalosporin antibiotic used to treat a wide range of bacterial infections, including pneumonia, meningitis, and sepsis. As with any medication, it carries a risk of side effects. While most hematological (blood-related) side effects are not a major concern, changes in white blood cell counts are possible and have been documented. The most common hematologic changes include leukopenia (decreased total WBCs) and eosinophilia (increased eosinophils), while true leukocytosis is significantly rarer.

The Rare Link Between Ceftriaxone and Leukocytosis

Clinical data and adverse event reports show that leukocytosis is a rare side effect of ceftriaxone, with an incidence of less than 0.1%. While this adverse reaction is not common, it can be clinically significant and warrants attention, especially in the context of a patient's underlying infectious process. In fact, many reports highlight leukopenia or neutropenia (decreased neutrophils) as the more frequent hematological complication associated with ceftriaxone. This emphasizes the need for a careful and comprehensive evaluation when a patient on ceftriaxone presents with an elevated white blood cell count.

Potential Mechanisms and Contributing Factors

The exact mechanism by which ceftriaxone induces leukocytosis is not fully understood, but several theories exist. In some cases, it is thought to be related to a type of hypersensitivity or allergic reaction. Case studies have documented ceftriaxone-induced leukocytoclastic vasculitis, a condition characterized by palpable skin rashes and elevated WBC counts, often with a high proportion of eosinophils. This suggests an immune-mediated reaction where the body's immune system overreacts to the drug, leading to an increase in circulating white blood cells.

Other potential mechanisms include:

Immune-mediated response: The drug or its metabolites may act as haptens, stimulating an immune response that leads to increased white blood cell production or release from the bone marrow.
Cross-reactivity: Some patients may experience cross-reactivity if they have allergies to other antibiotics, such as penicillin.
Underlying conditions: Patients with pre-existing conditions, particularly immunologic or hematologic disorders, may have a higher risk of experiencing adverse reactions that affect their blood cell counts.

Distinguishing Drug-Induced from Infection-Related Leukocytosis

One of the primary challenges in diagnosing drug-induced leukocytosis is distinguishing it from the leukocytosis caused by the infection the antibiotic is meant to treat. A patient on ceftriaxone for a bacterial infection would be expected to have an elevated white blood cell count. Clinical suspicion is key, especially if the WBC count remains unusually high or continues to rise despite clinical improvement of the infection. Important differentiating factors include a lack of clinical signs of ongoing infection and changes in the differential count.

Leukocytosis: Drug-Induced vs. Infection-Induced


Feature	Drug-Induced Leukocytosis (e.g., Ceftriaxone)	Infection-Induced Leukocytosis
Timing	Often occurs after several days or weeks of treatment; resolves after discontinuation.	Typically present at onset of infection; decreases as infection resolves.
'Left Shift'	Rarely shows a significant 'left shift' (increased immature neutrophils).	Frequently presents with a 'left shift' and toxic granulation of neutrophils.
Symptoms	Often associated with a rash or other signs of hypersensitivity, but can be asymptomatic.	Accompanied by other signs of infection, such as fever, localized pain, and purulence.
Differential Count	May show atypical patterns, such as prominent eosinophilia or lymphocytosis.	Typically a neutrophilic predominance in bacterial infections.
Clinical Course	WBC count should normalize relatively quickly after discontinuing the offending drug.	WBC count follows the course of the infection, normalizing as the patient recovers.

Other Hematologic Side Effects of Ceftriaxone

Beyond leukocytosis, ceftriaxone has been associated with several other blood count abnormalities. These side effects can range in severity and should be monitored with regular blood tests, especially during prolonged courses of therapy.

Leukopenia/Neutropenia: A reduction in the total number of white blood cells or specifically neutrophils is a more frequently reported side effect of ceftriaxone than leukocytosis, though it is still uncommon. This can lead to an increased risk of infection if severe enough.
Eosinophilia: A rise in the number of eosinophils, a type of WBC, is one of the most common hematologic adverse events associated with ceftriaxone, reported in up to 10% of patients in some studies. It is often a sign of an allergic or hypersensitivity reaction.
Thrombocytopenia/Thrombocytosis: Both a decrease (thrombocytopenia) and an increase (thrombocytosis) in platelet counts have been reported. Ceftriaxone-induced thrombocytopenia is typically immune-mediated and resolves after the drug is stopped.
Hemolytic Anemia: This is a rare but serious adverse effect where red blood cells are destroyed prematurely due to an immune reaction. Timely diagnosis and discontinuation of the drug are crucial.

Conclusion

While the answer to 'Can ceftriaxone cause leukocytosis?' is yes, it's crucial to understand that it is a rare phenomenon compared to other potential blood count changes like leukopenia and eosinophilia. The diagnosis of drug-induced leukocytosis is challenging and often relies on distinguishing it from the underlying infection. It is frequently associated with allergic or hypersensitivity reactions, and the WBC count typically returns to normal after the medication is discontinued. For patients receiving ceftriaxone, monitoring blood counts, especially during prolonged treatment, is important for identifying any potential adverse drug effects. For healthcare providers, recognizing the possibility of drug-induced leukocytosis and carefully evaluating the patient's overall clinical picture is vital for effective management.

For more detailed information on ceftriaxone side effects, consult comprehensive drug information resources such as Drugs.com.

Frequently Asked Questions

No, leukocytosis is a rare side effect of ceftriaxone, occurring in less than 0.1% of patients. Other blood count changes, such as eosinophilia and leukopenia, are reported more frequently.

The most common changes are an increase in eosinophils (eosinophilia) and a decrease in total white blood cells (leukopenia).

Doctors differentiate by assessing the entire clinical picture. They look for signs of a resolving infection, the presence of allergic reactions like a rash, and specific patterns in the differential white blood cell count, such as the absence of a 'left shift'.

Extremely high WBC counts ($>100,000/mm^3$) are unlikely to be caused by ceftriaxone alone and usually signal a more serious medical emergency. Drug-induced leukocytosis is typically more moderate.

You should not stop your medication on your own. Your doctor will monitor your blood counts and other symptoms. If drug-induced leukocytosis is suspected, the ceftriaxone will likely be stopped and an alternative antibiotic may be prescribed.

The elevated white blood cell count typically resolves within one to three weeks after discontinuing the offending medication.

Ceftriaxone is more likely to cause leukopenia (low white blood cells) or eosinophilia (high eosinophils) than true leukocytosis (high total white blood cells).