Can fosfomycin (antibiotic) induce fever in patients?

Fosfomycin and Fever: Association and Management

Fosfomycin can induce fever as an adverse reaction, though it occurs in less than 1% of patients according to FDA drug labeling data. 1

Evidence on Fosfomycin and Fever

Fever is not listed among the common adverse reactions of fosfomycin in the FDA drug label, which reports the most frequent adverse events as:

• Diarrhea (9.0%)
• Vaginitis (5.5%)
• Nausea (4.1%)
• Headache (3.9%)
• Dizziness (1.3%)

Fever is mentioned only as an uncommon adverse event occurring at a rate of less than 1% in clinical trials, regardless of drug relationship 1.

Risk Factors and Monitoring

When administering fosfomycin, particularly important considerations include:

1. Electrolyte imbalances: Recent evidence shows fosfomycin can cause significant electrolyte disturbances, particularly:

   • Decreased serum potassium (average drop of 0.6 mEq/L)
   • Decreased calcium (average drop of 0.7 mEq/L)
   • Decreased magnesium (average drop of 0.3 mg/dL)
   • Increased sodium levels (average increase of 4 mEq/L) 2

2. Higher risk populations: Patients with pre-existing kidney dysfunction and heart failure experience more pronounced electrolyte changes 2

3. Administration method: Electrolyte changes are more significant when fosfomycin is diluted with saline compared to 5% glucose solution 2

Clinical Approach to Fever During Fosfomycin Treatment

If a patient develops fever while on fosfomycin:

1. Evaluate for alternative causes: Since fever is an uncommon reaction to fosfomycin, first rule out other infectious causes:

   • Assess for progression of the original infection
   • Consider secondary infections, especially C. difficile (the most common enteric cause of fever in hospitalized patients) 3
   • Evaluate for other common hospital-acquired infections

2. Consider drug reaction: If other causes are ruled out, consider fosfomycin-induced fever:

   • Check for other signs of drug reaction
   • Evaluate timing of fever in relation to drug administration

3. Management options:

   • If fever is mild and the infection is responding to fosfomycin, consider continuing treatment with close monitoring
   • If fever is significant or accompanied by other concerning symptoms, consider alternative antimicrobial therapy based on culture results and local resistance patterns

Alternative Treatment Options

If fosfomycin must be discontinued due to fever or other adverse reactions, alternative options include:

• For complicated UTIs: Ceftazidime/avibactam, meropenem/vaborbactam, or aminoglycosides 4
• For uncomplicated UTIs: Nitrofurantoin or trimethoprim-sulfamethoxazole 4

Key Considerations

• Fosfomycin is generally well-tolerated with a favorable safety profile 5, 6
• The drug has gained renewed interest for treating multidrug-resistant infections 7
• When using intravenous fosfomycin, careful monitoring of electrolytes is essential, especially in patients with pre-existing kidney dysfunction or heart failure 2

In conclusion, while fever is a possible adverse effect of fosfomycin, it is relatively uncommon. If fever develops during fosfomycin treatment, clinicians should first rule out other more common causes before attributing it to the medication itself.