Understanding Vancomycin Infusion Reaction: What is the new name for red man syndrome?

October 7, 2025 •

3 min read

Over the past few years, the medical community has shifted away from the outdated and potentially insensitive term 'red man syndrome'. The syndrome is now more accurately and respectfully referred to as vancomycin infusion reaction (VIR) or vancomycin flushing syndrome (VFS). This change reflects a better understanding of the condition and a move toward more inclusive medical language.

Quick Summary

This article discusses vancomycin infusion reaction, the modern term for what was formerly known as red man syndrome. It explains the histamine-mediated, non-allergic nature of this reaction, its symptoms, and the factors that contribute to its occurrence. Learn about effective management strategies and important distinctions from true anaphylaxis.

Key Points

New Terminology: The preferred medical name is now vancomycin infusion reaction (VIR) or vancomycin flushing syndrome (VFS), replacing the outdated 'red man syndrome'.
Not a True Allergy: VFS is an anaphylactoid reaction, a non-immune-mediated histamine release, and does not involve the IgE antibodies of a true allergic response.
Rapid Infusion is the Cause: The reaction is primarily triggered by the rapid intravenous infusion of vancomycin, causing mast cells and basophils to release histamine.
Key Symptoms: Symptoms include an itchy, red rash on the face, neck, and torso, along with potential hypotension, weakness, and angioedema.
Treatment is Immediate: Management involves immediately stopping the vancomycin infusion, administering antihistamines, and restarting the infusion at a slower rate once symptoms resolve.
Prevention is Possible: The risk can be minimized by slowing the vancomycin infusion rate to at least 60 minutes for a 1-gram dose and potentially pre-treating high-risk patients with antihistamines.
Other Drugs Can Cause Similar Reactions: While vancomycin is the most common cause, other drugs like ciprofloxacin, rifampicin, and amphotericin B can also trigger histamine release.

The shift in medical terminology

Historically, the adverse reaction to the rapid infusion of vancomycin was widely known as 'red man syndrome' or 'red neck syndrome' due to the distinctive red, flushing rash it could cause, particularly on the face, neck, and upper body. However, this terminology has been retired by major medical societies, such as the Pediatric Infectious Diseases Society, in favor of more precise and culturally sensitive language. The preferred modern names are vancomycin infusion reaction (VIR) or vancomycin flushing syndrome (VFS).

The change was motivated by several factors. First, the old name could be construed as insulting to certain groups of people. Second, it placed an undue emphasis on the flushing, which is a prominent feature but not the only one, and may be less visible in patients with darker skin, potentially leading to a missed or delayed diagnosis. The new names more accurately describe the etiology and presentation of the condition, emphasizing that it is an infusion-related reaction to the drug vancomycin.

Pathophysiology: What causes the reaction?

Unlike a true allergic reaction, which is mediated by immunoglobulin E (IgE), vancomycin infusion reaction is an anaphylactoid hypersensitivity response. The reaction is not a true allergy and does not require prior exposure to the drug. Instead, it is triggered by the rapid infusion of vancomycin, which causes the direct, non-immune-mediated release of histamine from mast cells and basophils. The amount of histamine released is directly proportional to the dose and the speed of the vancomycin infusion.

Signs and symptoms

The clinical presentation of VFS can range from mild discomfort to severe, systemic symptoms. Symptoms typically begin within minutes of starting the infusion, although delayed reactions can sometimes occur.

Common signs and symptoms include:

An intense, pruritic (itchy) erythematous rash, usually on the face, neck, and upper torso.
Flushing of the skin.
Hypotension (low blood pressure).
Weakness or dizziness.
Tachycardia (rapid heartbeat).
Angioedema (swelling, particularly of the face).
Less common symptoms include chest or back pain, chills, and fever.

Diagnosis, treatment, and prevention

Diagnosis of VFS is primarily clinical, based on the characteristic symptoms appearing during or shortly after the vancomycin infusion. A critical step in management is differentiating VFS from a true anaphylactic reaction, which requires a different and more aggressive treatment approach, including epinephrine administration.

Immediate management involves:

Stopping the vancomycin infusion immediately.
Administering antihistamines, such as a combination of an H1-blocker (like diphenhydramine) and an H2-blocker (like cimetidine), to manage the histamine release.
Supportive care, which may include intravenous fluids for hypotension.

Prevention is key to managing this reaction.

Slowing the infusion rate is the most effective preventive measure. For example, administering a 1-gram dose over at least 60 minutes, or longer for higher doses.
Pre-treatment with antihistamines may be used for patients with a history of VFS or those at high risk.

Comparing VFS and anaphylaxis

It is crucial for healthcare professionals to distinguish between vancomycin infusion reaction and true anaphylaxis, as they have different underlying mechanisms and treatment protocols.


Feature	Vancomycin Infusion Reaction (VFS/VIR)	Anaphylaxis
Mechanism	Non-IgE-mediated direct mast cell and basophil degranulation, causing histamine release.	IgE-mediated, involving the immune system's allergic response.
Prior Exposure	Not required; often occurs during or after the first dose.	Requires prior exposure and sensitization to the allergen.
Onset	Typically within 4-10 minutes of infusion, but can be delayed.	Usually rapid, within seconds to minutes of exposure.
Key Symptoms	Primarily flushing, pruritus, rash on upper body, and possibly hypotension. Severe systemic signs like stridor or wheezing are less common.	Can involve widespread urticaria (hives), angioedema, respiratory distress (stridor, wheezing), severe hypotension, and cardiovascular collapse.
Primary Treatment	Stopping infusion and administering antihistamines.	Epinephrine, in addition to supportive care and antihistamines.

Conclusion

Vancomycin infusion reaction (VIR), previously known as 'red man syndrome,' is a common, non-allergic hypersensitivity response to the rapid infusion of vancomycin. Symptoms typically involve flushing and rash on the upper body and are caused by a direct, histamine-mediated reaction. Healthcare providers must be aware of the modern, respectful terminology and understand the pathophysiology to correctly manage the reaction by slowing the infusion rate and administering antihistamines. Differentiating VFS from a true anaphylactic event is vital to ensure patient safety and proper treatment. Appropriate management and prevention are crucial for patients receiving this important antibiotic. A thorough review of the topic is available in the StatPearls article, "Vancomycin Infusion Reaction".

Frequently Asked Questions

The name changed because 'red man syndrome' is considered outdated, potentially insensitive, and does not accurately describe the reaction in all patients, particularly those with darker skin. The new terms, vancomycin infusion reaction (VIR) or vancomycin flushing syndrome (VFS), are more precise and respectful.

No, it is not a true allergic reaction. It is an anaphylactoid reaction, meaning it is not mediated by the immune system's IgE antibodies. Instead, it is caused by the direct, non-immune release of histamine from mast cells and basophils.

The primary cause is the rapid intravenous infusion of the antibiotic vancomycin. The speed and dose of the infusion are directly related to the amount of histamine released and the severity of the reaction.

If a patient exhibits symptoms of VFS, the vancomycin infusion should be stopped immediately. Antihistamines are administered to manage the reaction, and once symptoms subside, the infusion may be restarted at a much slower rate.

While rare, cases of VFS have been reported with oral vancomycin, particularly in patients with impaired renal function or certain gastrointestinal conditions where systemic absorption is increased.

For mild cases, symptoms typically resolve within about 20 minutes after the infusion is stopped. Moderate-to-severe cases may take a few hours to resolve with appropriate treatment.

Although vancomycin is the most common cause, other medications that can trigger similar histamine-release reactions include ciprofloxacin, rifampicin, amphotericin B, and teicoplanin.