What is Drug Fever and How Can Cefuroxime Cause It?
Drug fever is a condition characterized by a high body temperature that coincides with the administration of a medication and resolves promptly after its discontinuation. It is a diagnosis of exclusion, meaning other causes of fever, such as infection, must be ruled out first. While many different drug classes can cause this reaction, antibiotics, and specifically cephalosporins like cefuroxime, are known culprits. Case studies, including one published in Pharmacotherapy, have specifically documented cefuroxime as a cause of drug-induced fever, with patients experiencing a fever that resolved within 30 hours of stopping the medication.
The mechanisms by which cefuroxime can lead to a fever are varied and often involve the body's immune response. A fever can be part of a broader hypersensitivity or allergic reaction to the drug. In other instances, it can be a direct pyrogenic effect related to how the drug is administered. In addition to these, there are two other specific conditions associated with cefuroxime use that can cause a fever, making the diagnostic process complex.
Potential Causes of Fever Associated with Cefuroxime
- Hypersensitivity or Allergic Reactions: A fever can be one of the signs of a hypersensitivity reaction to cefuroxime. These reactions can range from mild, with a skin rash or hives, to severe, with symptoms like swelling of the face and throat, trouble breathing, or a severe skin reaction like Stevens-Johnson Syndrome (SJS). If a fever is accompanied by these other symptoms, it is a medical emergency requiring immediate attention.
- Jarisch-Herxheimer Reaction: Patients receiving cefuroxime for certain conditions, most notably Lyme disease, may experience a Jarisch-Herxheimer reaction. This is not an allergic reaction but an immune response to the endotoxins released by bacteria dying off from the antibiotic. It is a temporary, self-limiting condition that can cause flu-like symptoms, including a short-term fever, chills, and headache.
- Clostridioides difficile (C. diff) Infection: Antibiotics can disrupt the normal balance of gut bacteria, allowing C. diff bacteria to overgrow and produce toxins. This can lead to severe diarrhea, abdominal pain, and fever. This complication can occur during cefuroxime treatment or even weeks to months after finishing the medication.
- General Drug-Induced Fever: As a diagnosis of exclusion, true drug-induced fever from cefuroxime often follows a specific pattern. It typically starts after several days of treatment, presents with a gradually increasing daily temperature, and then resolves quickly once the drug is stopped. Patients often feel better than their fever would suggest, a phenomenon known as relative bradycardia.
Differentiating Drug Fever from an Infection
When a fever occurs during cefuroxime treatment, it is critical to determine if it is a side effect of the medication or a sign of a persistent or secondary infection. The following table highlights key differences.
| Feature | Drug Fever | Infection-Induced Fever |
|---|---|---|
| Onset | Occurs days to weeks after starting medication. | Occurs concurrently with the infection and typically improves with successful treatment. |
| Fever Pattern | Often follows a gradually rising, high, and remittent pattern. | Variable pattern, but often follows the course of the infection being treated. |
| Associated Symptoms | May include relative bradycardia (inappropriately low heart rate for the fever), feeling "well" despite high temperature, or a skin rash. | Often accompanied by symptoms of the underlying infection (e.g., pain, discharge, localized signs). |
| Laboratory Results | May show signs of eosinophilia (increased eosinophils), but not always. | Lab results typically reflect the inflammatory response of the infection (e.g., elevated white blood cell count). |
| Response to Therapy | Resolves within 48-72 hours after stopping the offending drug. | Worsens or persists if the infection is not being effectively treated. |
What to Do If a Fever Develops During Treatment
If you or a patient develops a fever while taking cefuroxime, it is important not to immediately assume it is a side effect. The first step is to contact a healthcare provider for evaluation. They will help determine the cause of the fever and the appropriate course of action. Do not stop taking the antibiotic without medical advice, as this could lead to the recurrence or worsening of the infection.
The healthcare provider will likely review your complete list of symptoms, perform an examination, and may order laboratory tests to look for signs of infection or allergic reaction. If they suspect a drug fever, they may recommend switching to a different class of antibiotic or discontinuing the medication, depending on the severity of the original infection and your overall health. If the fever resolves quickly after stopping cefuroxime, it strongly supports a diagnosis of drug fever. Re-exposure to the drug to confirm the diagnosis is often not recommended due to the risk of a more severe reaction.
Conclusion
While not a common side effect, cefuroxime can indeed cause a fever through several mechanisms, including hypersensitivity reactions, the Jarisch-Herxheimer reaction, and C. difficile infection. The key for both patients and clinicians is recognizing that not all fevers during antibiotic treatment are due to a failed or new infection. Understanding the signs of drug fever and other antibiotic-related complications is vital for making an accurate diagnosis and preventing inappropriate or harmful treatment delays. As with any potential adverse reaction, prompt medical consultation is necessary to ensure patient safety.
For more information on drug reactions and their management, the National Institutes of Health (NIH) is a valuable resource: https://www.ncbi.nlm.nih.gov/books/NBK599503/
