Can Fosfomycin Cause Fever? Understanding This Rare Side Effect

October 13, 2025 •

4 min read

Fever is listed as an uncommon adverse event for fosfomycin, occurring in less than 1% of patients during clinical trials. While many people experience no issues, it is important to understand the rare instances where can fosfomycin cause fever or when a fever might indicate another problem entirely.

Quick Summary

Fosfomycin can cause a rare drug-induced fever, but this symptom is more often a sign of a persistent or worsening infection, a serious allergic reaction, or C. difficile colitis. Prompt medical evaluation is critical to determine the true cause of the fever.

Key Points

Rare Side Effect: Fever is an uncommon adverse effect of fosfomycin, reported in less than 1% of patients during clinical trials.
Differential Diagnosis: A fever during fosfomycin treatment is more likely caused by a worsening infection, C. difficile-associated diarrhea, or a serious allergic reaction than by the drug itself.
Distinguishing Drug Fever: A true drug-induced fever may not have an apparent cause and can resolve within a few days of stopping the medication.
Watch for Worsening UTI: If your original UTI symptoms, including fever, do not improve after 2-3 days, it could mean the infection isn't responding to the treatment.
Consider C. difficile: Severe, watery or bloody diarrhea combined with fever could indicate a serious colon infection that can occur during or after antibiotic use.
Seek Immediate Care: An accompanying rash, hives, swelling, or difficulty breathing requires emergency medical help, as it may signal a severe allergic reaction.
Professional Evaluation is Key: Because a fever could signify different problems, it is crucial to consult a healthcare provider to determine the cause and appropriate course of action.

Understanding the Rarity of Fever as a Fosfomycin Side Effect

Fosfomycin (brand name Monurol) is an antibiotic most commonly prescribed as a single, oral dose to treat uncomplicated urinary tract infections (UTIs) in women. Its unique mechanism of action makes it a valuable tool against resistant bacteria. For most people, the medication is well-tolerated, with the most common side effects being mild and related to the gastrointestinal system, such as diarrhea, nausea, and headache.

When a fever occurs during or shortly after taking fosfomycin, it is rarely due to the medication itself. Instead, it most often points to one of three other possibilities: the underlying infection is not responding, it has spread, or a more serious, albeit rare, side effect is occurring. Distinguishing between these causes is crucial for appropriate treatment and patient safety.

Unpacking Potential Causes of Fever During Fosfomycin Treatment

When a patient develops a fever after taking fosfomycin, healthcare providers must consider a few different potential etiologies. This diagnostic process is known as a differential diagnosis.

Ineffective or Worsening Infection

Fosfomycin is primarily used for uncomplicated UTIs. A persistent or worsening fever after the dose could indicate that the infection has not been adequately treated. This could happen if the bacteria are resistant to fosfomycin, or if the infection has progressed to the kidneys, a condition known as pyelonephritis. Pyelonephritis is a more serious condition that causes symptoms including fever, chills, and back or flank pain. If your symptoms do not improve within 2 to 3 days after taking fosfomycin, or if they get worse, you should contact your doctor immediately.

Drug Fever: A Rare Hypersensitivity Reaction

True drug fever is an adverse reaction to a medication that causes an elevation in body temperature. It is caused by an immune-mediated hypersensitivity response. In the case of fosfomycin, a drug-induced fever is an uncommon side effect, appearing in less than 1% of patients in clinical trials. The onset can vary but often occurs within 7 to 10 days of starting a new medication. A key feature of drug fever is that it typically resolves within 48 to 72 hours of discontinuing the offending drug, though it can sometimes take longer. The fever can be mild or high and may be accompanied by a rash or elevated white blood cell counts. In some cases, patients may feel surprisingly well despite having a high temperature, though this isn't always the case.

Clostridium difficile-Associated Diarrhea (CDAD)

All antibiotics, including fosfomycin, can disrupt the natural balance of bacteria in the colon. This disruption can allow a bacterium called Clostridium difficile (C. difficile) to overgrow and produce toxins. The resulting condition, CDAD, is a potentially severe intestinal infection characterized by severe diarrhea (which may be watery or bloody), abdominal cramps, and fever. CDAD can occur during or even weeks to months after antibiotic treatment. It is a serious complication that requires prompt medical attention.

Other Allergic Reactions (Anaphylaxis)

While rare, a severe allergic reaction, or anaphylaxis, is a potential cause of fever related to fosfomycin. Anaphylaxis is a medical emergency that involves a widespread, multi-system allergic response. Symptoms can include hives, swelling of the face, lips, tongue, or throat, and difficulty breathing, often accompanied by fever. If you experience these symptoms, seek emergency medical care immediately.

Comparison Table: Fever Causes during Fosfomycin Therapy


Feature	Drug Fever (Fosfomycin Side Effect)	Ineffective UTI Treatment	C. difficile Colitis (CDAD)	Severe Allergic Reaction (Anaphylaxis)
Incidence	Rare (<1%)	Variable	Rare	Very rare
Timing of Onset	Typically 7–10 days after starting the drug, but can be earlier or later	Persistent or worsening fever 2–3 days after dose	During or weeks/months after treatment	Immediately after taking the dose
Key Symptoms	Fever, sometimes with rash or eosinophilia. Often feel disproportionately well.	Fever, chills, lower back/side pain, painful urination.	Watery/bloody diarrhea, severe stomach pain/cramps, fever.	Hives, rash, swelling of face/tongue/throat, difficulty breathing, fever.
Resolution	Resolves within 48-72 hours of stopping fosfomycin.	Requires a different antibiotic.	Requires specific treatment for C. difficile.	Emergency medical treatment.

When to Seek Immediate Medical Attention

While mild side effects may resolve on their own, certain symptoms warrant immediate medical attention. It is crucial to be vigilant for signs of more serious complications.

Severe Diarrhea

Contact your healthcare provider right away if you experience watery or bloody diarrhea, especially if accompanied by stomach cramps and fever. This could be a sign of Clostridium difficile infection, which needs specific treatment.

Allergic Reaction

If you experience hives, rash, swelling of the face, lips, tongue, or throat, or difficulty breathing, seek emergency medical help immediately. These are symptoms of a severe allergic reaction.

Worsening UTI Symptoms

If your urinary tract infection symptoms, including fever, do not improve within 2 to 3 days or get worse, contact your doctor. This could mean the infection is not responding to fosfomycin and may require a different course of treatment. A fever combined with back or flank pain may indicate a kidney infection (pyelonephritis), which is not treated by a single dose of oral fosfomycin.

Conclusion

Fever is a possible but uncommon adverse effect of fosfomycin. When a fever occurs during treatment, it is much more likely to be caused by a persistent or worsening infection, or a severe complication such as C. difficile colitis or a serious allergic reaction. It is important not to dismiss a fever, as it could be a crucial signal of a developing problem. If a fever arises, especially if accompanied by other concerning symptoms, you should contact a healthcare professional to determine the underlying cause and ensure you receive the correct and most effective treatment. Do not attempt to treat a persistent fever yourself without first consulting a doctor, as it may mask the symptoms of a more serious issue.

For more detailed information on fosfomycin side effects and warnings, you can visit the official DailyMed entry for the drug.

Frequently Asked Questions

Fever is a rare side effect of fosfomycin, occurring in less than 1% of patients during clinical trials. If you develop a fever, it is more likely caused by a persistent or worsening infection, or another underlying issue.

If you develop a fever, you should contact your doctor promptly. It is important to determine the cause, as it could be a sign that the infection is not responding to treatment or that a different complication is developing.

Yes, a fever that persists or worsens after taking fosfomycin could be a sign that the original urinary tract infection is not being cleared by the medication or has spread, possibly to the kidneys. Contact your healthcare provider if your symptoms don't improve within 2 to 3 days.

You should seek immediate medical attention for symptoms such as severe, watery, or bloody diarrhea; rash, hives, or swelling of the face, tongue, or throat; difficulty breathing; or severe back or flank pain.

Yes, a severe allergic reaction (anaphylaxis) to fosfomycin is a possibility, though it is very rare. Such a reaction can include fever along with other symptoms like hives, swelling, and trouble breathing.

Drug fever is a diagnosis of exclusion and is caused by the body's reaction to the medication itself. A fever from a bacterial infection is a normal inflammatory response to the microbes. With drug fever, the fever typically resolves after discontinuing the drug, while with an infection, the fever persists until the infection is treated.

Before taking any over-the-counter medication, you should consult your doctor, as it can mask important symptoms. The priority is to address the underlying cause of the fever, not just treat the symptom itself.