Can Antibiotics Cause a Drug Fever?

October 12, 2025 •

4 min read

Yes, antibiotics are the most frequent cause of drug-induced fevers, a phenomenon that is often overlooked or misdiagnosed as a worsening infection. This adverse reaction, which can be triggered by a hypersensitivity response, typically begins days to weeks after starting the new medication.

Quick Summary

Drug fever is a rise in body temperature caused by a medication, not infection, and antibiotics are a common culprit. Symptoms include fever and sometimes a rash, and they resolve after stopping the medication. Correct diagnosis is crucial to avoid inappropriate or unnecessary treatments.

Key Points

Prevalence: Antibiotics are the most common cause of drug fever, with beta-lactams and sulfonamides being frequent culprits.
Mechanism: Drug fever is often caused by a hypersensitivity reaction, where the immune system misidentifies the drug as a threat and releases fever-inducing substances.
Delayed Onset: Unlike a direct adverse effect, drug fever typically appears 7 to 10 days after starting the medication, though timing can vary.
Diagnostic Challenge: Diagnosis can be difficult, as it's a diagnosis of exclusion that requires ruling out other causes of fever, especially in patients with existing infections.
Key Symptoms: Key signs include fever (which may not correlate with other typical signs of being unwell) and sometimes a rash. Patients may exhibit relative bradycardia.
Treatment: The definitive treatment is to discontinue the offending antibiotic, which usually leads to a resolution of the fever within 48 to 72 hours.

Understanding Drug Fever

Drug fever is a febrile reaction that occurs in response to a medication and resolves after the drug is discontinued. It is a diagnosis of exclusion, meaning that all other potential causes of fever, particularly infection, must be ruled out first. This can be particularly challenging when a patient is taking antibiotics to treat an existing infection. In fact, approximately one-third of all drug-induced fevers are caused by antibiotics.

Unlike an infectious fever, which is a key symptom of the body fighting a pathogen, drug fever is a side effect of the medication itself. It can be caused by several mechanisms, most commonly an immune-mediated hypersensitivity reaction. The fever may be low-grade or high, continuous or intermittent, and often presents with other symptoms, or sometimes none at all.

Mechanisms of Antibiotic-Induced Drug Fever

There are several ways antibiotics can cause a drug fever, reflecting different types of adverse drug reactions:

1. Hypersensitivity Reactions

This is the most common mechanism behind drug fever. The body's immune system mistakenly identifies the antibiotic or one of its metabolites as a threat. This triggers an immune response, releasing endogenous pyrogens (fever-inducing substances like cytokines) that act on the hypothalamus to raise the body's temperature set point. Common antibiotics known to cause this type of reaction include penicillins, cephalosporins, and sulfonamides.

2. Altered Thermoregulatory Mechanisms

Some drugs can interfere with the body's ability to regulate its temperature. While more common with certain psychotropic or anticholinergic drugs, some antibiotics can also impact this system, either by increasing heat production or decreasing heat dissipation.

3. Administration-Related Fever

In rare cases, fever can be caused by the administration process itself. This can be due to contamination of an intravenous solution with endotoxins or other pyrogens. This mechanism is less common today due to modern manufacturing standards, but was once a known issue with drugs like vancomycin before reformulation.

4. Pharmacologic Effects

The direct pharmacological action of a drug can also cause a fever. For example, the Jarisch-Herxheimer reaction can occur when certain bacteria (such as those causing syphilis or Lyme disease) are killed by an antibiotic, releasing inflammatory substances that cause a transient fever.

5. Idiosyncratic Reactions

Some individuals have a genetic predisposition or an unexplained, unique reaction to a drug that can trigger a fever. These idiosyncratic reactions are not immune-mediated and are difficult to predict.

Distinguishing Drug Fever from Infectious Fever

For clinicians and patients alike, telling the difference between a new infection, a worsening infection, and drug fever can be a challenge. Making the correct distinction is vital to prevent unnecessary and potentially harmful diagnostic or treatment interventions. The following table highlights key differences:


Feature	Drug Fever	Infectious Fever
Onset	Typically occurs 7–10 days after starting the drug, but can vary.	Can occur at any point during or before treatment.
Symptom Pattern	Fever is often the main symptom; patients may appear relatively well despite high temperatures.	Accompanied by signs and symptoms of an active infection (e.g., wound infection, respiratory distress).
Heart Rate	Relative bradycardia (heart rate is lower than expected for the temperature) may be present.	Heart rate typically increases proportionally with temperature (Liebermeister's rule).
Supporting Signs	May present with a rash or blood test abnormalities like eosinophilia, but not always.	Associated with a specific infectious source, with potential lab findings consistent with infection (e.g., high C-reactive protein).
Resolution	Resolves within 48–72 hours of discontinuing the medication.	Resolves as the underlying infection is treated effectively.

Specific Antibiotics Implicated in Drug Fever

While any antibiotic can theoretically cause a drug fever, some are more commonly associated with this adverse effect. These include:

Beta-Lactams: Penicillins (e.g., ampicillin, piperacillin) and cephalosporins (e.g., cefuroxime, cephalexin) are frequently implicated due to common hypersensitivity reactions.
Sulfonamides: Drugs like trimethoprim-sulfamethoxazole are well-known causes of drug fever.
Vancomycin: While less common with modern formulations, older versions of vancomycin were often associated with fever due to impurities.
Minocycline: This tetracycline antibiotic is also linked to drug-induced fever, sometimes as part of a more serious hypersensitivity syndrome.
Others: Isoniazid, rifampin, and carbapenems like imipenem/cilastatin can also cause drug fever.

Management and Treatment of Drug Fever

Managing a suspected drug fever requires a systematic approach. The first and most critical step is to have a healthcare provider identify and, if safe, discontinue the suspected medication. It is important that patients do not stop taking an antibiotic on their own without medical advice, as this could worsen an underlying infection.

Upon discontinuation of the causative drug, the fever typically subsides within 48 to 72 hours. Supportive care can be provided to manage symptoms, but the fever itself is generally benign and resolves with the removal of the offending agent. In cases where a drug cannot be stopped, a chemically unrelated alternative might be prescribed.

Conclusion

While a less common occurrence, the possibility of an antibiotic causing a drug fever is a real clinical concern. The ability to distinguish it from a normal infectious fever is critical for effective patient management and avoiding unnecessary tests and treatments. By recognizing the specific signs, patterns, and typical causative agents, healthcare professionals can accurately diagnose and resolve this adverse reaction, allowing for proper treatment of the patient's underlying condition. Awareness is key, and discontinuing the medication under medical supervision is the definitive step towards confirmation and resolution. This phenomenon highlights the complex relationship between medications and the body's immune and physiological systems, even when the medication is intended to heal. For more in-depth information, you can read about the clinical diagnosis and therapy for drug fever from a case report published in Frontiers in Surgery.

Frequently Asked Questions

A drug fever is an adverse drug reaction characterized by an elevated body temperature caused by a medication. It is diagnosed after ruling out other potential causes of fever, such as an infection.

While many antibiotics can cause drug fever, some of the most commonly implicated include beta-lactam antibiotics (penicillins and cephalosporins), sulfonamides (e.g., trimethoprim-sulfamethoxazole), and vancomycin.

The onset of drug fever is highly variable but most typically occurs 7 to 10 days after starting a medication for the first time. However, it can also manifest sooner or much later.

Clinical clues can differentiate them. With drug fever, the fever is often disproportionately high for how well the patient looks and may be accompanied by relative bradycardia. An infectious fever usually has corresponding signs of illness and a pulse rate that rises with the temperature.

Do not stop taking your medication. It is important to contact your doctor or pharmacist immediately. They can evaluate your symptoms and determine if it's safe to switch to a different antibiotic or if an underlying infection is still present.

The primary treatment is to discontinue the antibiotic under a doctor's supervision. The fever will typically resolve within 48 to 72 hours. Supportive care, like staying hydrated and using light bedding, can help with symptoms in the meantime.

Drug fever is generally benign and resolves completely after the offending medication is stopped. If the reaction is part of a more serious condition, like Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), there can be more significant complications.