Which antibiotics increase WBC? A Look at Paradoxical Leukocytosis

October 13, 2025 •

3 min read

While antibiotics typically lower white blood cell (WBC) counts by resolving infection, certain medications can cause a paradoxical increase. Understanding which antibiotics increase WBC and why is crucial for accurate diagnosis and patient management.

Quick Summary

An elevated white blood cell count (leukocytosis) is a known side effect of some medications, including certain antibiotics. This reaction is often linked to hypersensitivity syndromes or immunomodulatory effects of the drugs.

Key Points

Paradoxical Effect: While antibiotics should lower WBC by fighting infection, some can cause a paradoxical increase (leukocytosis).
DRESS Syndrome: A primary cause is Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), a severe hypersensitivity reaction involving rash, fever, and organ damage.
Vancomycin: This antibiotic is one of the most frequent causes of antibiotic-induced DRESS syndrome and associated leukocytosis.
Beta-Lactams: Penicillins (e.g., piperacillin-tazobactam) and cephalosporins can also trigger hypersensitivity reactions leading to high WBC counts.
Sulfonamides: Drugs like trimethoprim-sulfamethoxazole are also commonly implicated in causing DRESS syndrome and elevated WBCs.
Eosinophilia: The increase in WBC is often characterized by a specific rise in eosinophils, a hallmark of allergic and drug reactions.
Clinical Action: If a drug-induced leukocytosis is suspected, the primary action is to stop the offending medication immediately.

The Standard Role of WBC and Antibiotics

White blood cells (WBCs), or leukocytes, are a critical component of the body's immune system. During a bacterial infection, the body increases WBC production to fight pathogens. This rise in WBC count is known as leukocytosis and indicates infection. As antibiotics clear the infection, the stimulus for increased WBCs decreases, leading to an expected drop in WBC count.

The Paradox: When Antibiotics Increase WBC Counts

Unexpectedly, some antibiotics can elevate WBC counts, a phenomenon called drug-induced leukocytosis. This can occur due to severe allergic reactions, direct effects on bone marrow, or specific drug-induced syndromes. The increase can be in neutrophils (neutrophilia) or, more specifically, eosinophils (eosinophilia).

Mechanisms Behind Antibiotic-Induced Leukocytosis

Antibiotic-associated leukocytosis can stem from several processes:

Drug Hypersensitivity Syndromes: Severe reactions like DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) are a major cause. DRESS is a serious, potentially fatal reaction with rash, fever, organ issues, marked eosinophilia, and leukocytosis.
Immunomodulation: Some antibiotics have effects on the immune system beyond killing bacteria. Certain fluoroquinolones, for instance, might boost factors stimulating granulocyte and macrophage growth.
Bone Marrow Stimulation: Though less common, some drugs can directly stimulate the bone marrow to produce more white blood cells. This effect is sometimes associated with antibiotics, alongside drugs like corticosteroids or lithium.
Underlying Unresolved Infection: A rising WBC count might also signal that the antibiotic is ineffective or that a secondary infection is present.

Antibiotics Associated with Increased WBC

While many antibiotics can cause hypersensitivity, some are more often linked to significant leukocytosis, especially eosinophilia, as part of DRESS syndrome. This group includes Beta-Lactams (Penicillins and Cephalosporins), Vancomycin, and Sulfonamides. Penicillins such as piperacillin-tazobactam and amoxicillin have been associated with DRESS syndrome. Vancomycin is frequently cited in relation to DRESS syndrome, with reactions typically appearing 2 to 9 weeks after starting. Sulfonamides like trimethoprim-sulfamethoxazole are also considered high-risk for DRESS syndrome. Other antibiotics implicated include Fluoroquinolones, Minocycline, and Antituberculosis Drugs like rifampin and isoniazid.

Comparison of Antibiotic Effects on WBC


Antibiotic Class/Drug	Expected Effect on WBC (with successful treatment)	Paradoxical Effect (Leukocytosis)	Common Mechanism for Increase
Beta-Lactams	Decrease	Increase (often eosinophilia)	Hypersensitivity, DRESS Syndrome
Vancomycin	Decrease	Significant Increase (eosinophilia)	DRESS Syndrome
Sulfonamides	Decrease	Increase (eosinophilia)	DRESS Syndrome
Fluoroquinolones	Decrease	Potential Increase	Immunomodulation, stimulation of colony-stimulating factors

Clinical Significance and Management

An unexpected rise in WBC during antibiotic treatment requires careful assessment to differentiate between a drug reaction, a new or worsening infection, or other causes of leukocytosis. If DRESS syndrome is suspected based on symptoms, the critical first step is discontinuing the causative drug. Supportive care and systemic corticosteroids may also be used to manage the immune response.

Conclusion

While antibiotics typically reduce WBC counts by resolving infection, a paradoxical increase can occur, often indicating a significant drug hypersensitivity reaction like DRESS syndrome. Vancomycin, beta-lactams, and sulfonamides are commonly implicated. Clinicians should be aware of this possibility, as recognizing antibiotic-induced leukocytosis is vital for prompt diagnosis, stopping the offending drug, and appropriate management.

For more in-depth information on drug-induced blood disorders, a valuable resource is the {Link: NCBI Bookshelf https://www.ncbi.nlm.nih.gov/books/NBK560882/}.

Frequently Asked Questions

Yes, typically an increased WBC count signifies an infection as the body mounts an immune response. However, when it occurs or worsens during antibiotic therapy, it can paradoxically signal a drug reaction rather than a failing treatment.

DRESS syndrome stands for Drug Reaction with Eosinophilia and Systemic Symptoms. It's a severe, delayed, and potentially fatal drug hypersensitivity reaction characterized by a widespread rash, fever, a high count of eosinophils (a type of WBC), and internal organ involvement.

Vancomycin is one of the most frequently reported antibiotics to cause DRESS syndrome, which prominently features leukocytosis with eosinophilia.

Yes, penicillins and related beta-lactam antibiotics can cause hypersensitivity reactions, including DRESS syndrome, which can lead to a high WBC count, particularly a high eosinophil count.

DRESS syndrome typically has a delayed onset, appearing anywhere from two to nine weeks after the initial exposure to the causative drug.

Yes, it can be very dangerous because it often signifies a severe systemic reaction like DRESS syndrome, which has a mortality rate of approximately 10% and can cause significant organ damage.

The most important step is to identify and discontinue the antibiotic causing the reaction. Further treatment often involves supportive care and may include systemic corticosteroids to control the severe inflammation associated with conditions like DRESS syndrome.