Understanding the Risks: Does Ampicillin Cause Neutropenia?

October 13, 2025 •

4 min read

While uncommon, isolated cases have confirmed that ampicillin can cause neutropenia, with one report detailing its occurrence in pediatric patients receiving high-dose therapy. This adverse drug reaction is generally reversible upon discontinuation of the medication, but it highlights the importance of awareness among clinicians and patients.

Quick Summary

Ampicillin, a penicillin-class antibiotic, can in rare cases induce neutropenia, a condition characterized by a reduced neutrophil count. Risk factors include high doses and prolonged therapy, and it is usually reversible upon ceasing the medication. Patients should monitor for signs of infection.

Key Points

Rarity: Neutropenia from ampicillin is uncommon, with some reports noting it is extremely rare, especially at lower doses.
Risk Factors: High-dose or prolonged therapy, often involving intravenous administration, increases the risk of neutropenia.
Timing: The condition typically develops after several days to a few weeks of treatment.
Reversibility: Ampicillin-induced neutropenia is generally reversible upon discontinuation of the drug.
Mechanism: The reaction is usually idiosyncratic, possibly involving an immune-mediated response or direct bone marrow suppression.
Symptoms: Symptoms are often related to the infections that arise due to a compromised immune system, most notably fever.
Management: The primary treatment is to stop the offending drug. In severe cases, supportive care and G-CSF may be needed.

Ampicillin is a widely used penicillin-class antibiotic prescribed to treat a variety of bacterial infections, such as respiratory tract infections, urinary tract infections, and meningitis. Like all medications, it carries a risk of side effects. One of the less common, but clinically significant, adverse effects associated with antibiotics, particularly beta-lactams, is neutropenia—a low count of neutrophils, a crucial type of white blood cell for fighting infection.

What is Neutropenia?

Neutropenia is defined as a reduction in the absolute neutrophil count (ANC) below 1,500 cells/mm³ for adults. Neutrophils are the body's first line of defense against bacterial and fungal infections. A low count weakens the immune system, making a person more susceptible to infections. The severity of neutropenia is typically graded as mild (ANC 1,000–1,500), moderate (ANC 500–1,000), or severe (ANC <500). In some severe cases, also known as agranulocytosis, the neutrophil count is extremely low.

How Ampicillin Causes Neutropenia

Though the exact mechanism for antibiotic-induced neutropenia is not fully understood, it is most often considered an idiosyncratic reaction—meaning it occurs unpredictably in a small number of people. The two main mechanisms believed to be involved are immune-mediated destruction of neutrophils and direct toxic effects on the bone marrow:

Immune-Mediated Reaction: In this scenario, the drug acts as a hapten, attaching to the surface of neutrophils. The body's immune system then recognizes this combination as foreign and produces antibodies to destroy the neutrophils. For this to occur, the drug's presence is often continuously required.
Direct Bone Marrow Toxicity: The drug or its metabolites may directly suppress the production of neutrophils in the bone marrow, leading to a decreased output of these cells. This can result in a maturation arrest in the development of granulocytic cells, as noted in some pediatric cases of ampicillin-induced neutropenia.

Identifying Ampicillin-Induced Neutropenia

Recognizing neutropenia is crucial for timely management. However, many patients may not experience symptoms from the low neutrophil count itself, but rather from the infections that develop as a result.

Common signs and symptoms of a possible infection include:

Fever, often one of the first and most telling signs.
Sore throat or mouth ulcers.
Fatigue or general feeling of being unwell.
Other signs of infection, such as diarrhea, pain, or redness around an infection site.

In documented cases, ampicillin-induced neutropenia often occurs after a period of treatment, typically developing within a few weeks of starting therapy. The onset can be more rapid if there has been previous exposure to the drug.

Risk Factors and Incidence

Ampicillin-associated neutropenia is rare, particularly with standard doses. However, certain factors can increase the risk:

High-Dose Therapy: Case reports frequently describe neutropenia occurring after high-dose ampicillin, sometimes in pediatric patients.
Prolonged Treatment: A longer course of therapy, particularly with intravenous administration, is associated with a higher risk.
Age: Younger age has been identified as a risk factor in some studies concerning antibiotic-induced neutropenia in children.

Comparing Ampicillin with Other Antibiotics

While ampicillin can cause neutropenia, its incidence is generally considered very low. Other beta-lactam antibiotics have also been linked to neutropenia, sometimes with higher reported rates depending on the study and patient population. Below is a comparison table based on a study of antibiotic-induced neutropenia in patients receiving outpatient parenteral therapy.


Antibiotic	Combined Incidence (per 100 courses)	Key Study Findings
Vancomycin	5.6 (3.8–7.9)	Highest risk in the study cohort.
Ceftriaxone	3.3 (1.9–5.4)	High risk among antibiotics studied.
Ampicillin	2.0 (0.3–7.9)	Low incidence reported in this study.
Cloxacillin	1.9 (0.3–7.5)	Low incidence.
Piperacillin-tazobactam	1.4 (0.5–3.1)	Low incidence.
Penicillin G	1.4 (0–8.5)	Low incidence.

This data highlights that while ampicillin is a potential cause, other antibiotics, even within the same class, can carry a higher risk of inducing neutropenia, underscoring the importance of careful patient monitoring.

Management and Recovery

If ampicillin-induced neutropenia is suspected, prompt action is necessary to ensure patient safety and rapid recovery. The primary course of action involves discontinuing the drug.

Immediate Discontinuation: As the most important step, the prescribing physician will immediately stop the ampicillin therapy.
Monitoring Blood Counts: The patient's blood counts, especially the absolute neutrophil count, will be regularly monitored. In most documented cases of ampicillin-induced neutropenia, the neutrophil count has returned to normal within days to a few weeks after stopping the medication.
Treatment of Underlying Infection: Since the patient's immune system is compromised, any infection that develops must be treated promptly. Broad-spectrum antibiotics may be used to manage febrile neutropenia. Care must be taken to choose an antibiotic from a different structural class to avoid cross-reactivity.
Supportive Care: Depending on the severity, supportive care may be necessary. In some severe cases, particularly if the neutropenia is profound, granulocyte colony-stimulating factor (G-CSF) might be administered to accelerate neutrophil recovery.

It is vital for patients to be aware of the signs of infection and to contact their healthcare provider immediately if they experience fever or other symptoms, especially if they are on a prolonged course of ampicillin.

Conclusion

While a rare adverse reaction, ampicillin can cause neutropenia, especially with high doses or extended treatment periods. The condition is typically reversible once the medication is stopped, and with careful monitoring and management, the outcome is often positive. The key is vigilance—for both healthcare providers prescribing prolonged or high-dose courses and for patients who should report any concerning symptoms, particularly fever, promptly. Awareness of this potential side effect, though infrequent, remains an essential component of safe medication practice. You can find more information about adverse drug events on the FDA website.

Frequently Asked Questions

Neutropenia is a rare side effect of ampicillin, particularly with standard oral doses. It is more frequently reported with high-dose, prolonged, and often intravenous therapy.

Symptoms of neutropenia are often related to subsequent infections and can include fever, sore throat, mouth ulcers, or increased fatigue. It's important to contact your doctor if you experience these symptoms while on treatment.

Risk factors can include high-dose or prolonged ampicillin therapy, particularly via intravenous administration. In some studies, younger age has also been identified as a potential risk factor in pediatric patients.

Diagnosis typically involves a blood test called a complete blood count (CBC) to check for low neutrophil levels. A doctor will also consider the timing relative to when ampicillin therapy began.

The most important step is to immediately stop the ampicillin therapy. Your doctor will monitor your blood counts, and if fever or infection occurs, supportive care and antibiotics from a different drug class may be administered.

Yes, other penicillin-class antibiotics, such as methicillin, nafcillin, and cloxacillin, have also been reported to cause neutropenia. Some may even have a higher associated risk than ampicillin.

In most documented cases, the condition is reversible, and neutrophil counts return to normal within a few days to a couple of weeks after stopping the medication.