Should intravenous (IV) iron be administered during an active infection?

IV Iron Should Not Be Administered During Active Infection

Intravenous (IV) iron should be avoided during active infection and should only be administered after the infection has completely resolved. 1 This recommendation is based on moderate-quality evidence showing an increased risk of infection with IV iron administration.

Evidence for Increased Infection Risk with IV Iron

The most comprehensive evidence comes from a 2021 systematic review and meta-analysis of 154 randomized controlled trials involving 32,762 participants, which found:

• IV iron was associated with a 16% increased risk of infection compared to oral iron or no iron (RR, 1.16; 95% CI, 1.03-1.29) 2
• This translates to approximately 16 more infections per 1,000 patients receiving IV iron
• The association was particularly strong in patients with inflammatory bowel disease (RR, 1.73; 95% CI, 1.11-2.71) 2

Biological Plausibility

There is strong biological plausibility for this recommendation:

1. Iron is required for growth by almost all human pathogens 2
2. IV iron administration increases levels of non-transferrin-bound iron, which can:
   • Be utilized by pathogens for growth
   • Impair T-cell and neutrophil function
   • Convert benign bacterial colonization into virulent infection 1
3. Common bacteria like Staphylococcus aureus have developed iron acquisition mechanisms that increase their pathogenicity 1

Clinical Practice Guidelines

Multiple clinical guidelines consistently recommend against IV iron during active infection:

• The National Comprehensive Cancer Network (NCCN) explicitly states: "Patients with active infection should not receive IV iron therapy" 2, 1
• The American College of Hematology, KDIGO, and British Society of Gastroenterology all recommend avoiding or suspending IV iron during active infections 1
• FDA labeling for iron sucrose (Venofer) warns about potential adverse effects, though does not specifically mention infection risk 3

Alternative Management Approaches

When a patient has both iron deficiency and active infection:

1. First priority: Complete antibiotic treatment and resolve the infection 1
2. Alternative approaches during infection:
   • Consider oral iron supplementation instead of IV iron 1
   • If oral iron is not feasible, consider erythropoiesis-stimulating agents (ESAs) with minimal IV iron 1
   • Note: Separate oral iron administration from certain antibiotics (tetracyclines, ciprofloxacin) by at least 2-3 hours due to decreased bioavailability 1

Special Considerations

• Timing: Wait until the infection is fully resolved before administering IV iron 1, 4
• Coordination: When IV iron is needed, carefully coordinate the timing of antibiotics, IV iron, and any chemotherapy to minimize infection risk 1
• Monitoring: All patients receiving IV iron require periodic monitoring of hematologic and iron parameters 3

Benefits of IV Iron When Appropriate

While IV iron should be avoided during active infection, it does provide significant benefits in appropriate clinical scenarios:

• Increased hemoglobin levels (MD, 0.57 g/dL; 95% CI, 0.50-0.64 g/dL) 2
• Reduced need for red blood cell transfusions (RR, 0.83; 95% CI, 0.76-0.89) 2
• Improved treatment response rates compared to oral iron or no iron (RR, 1.46; 95% CI, 1.32-1.60) 2

Common Pitfalls to Avoid

1. Administering IV iron during active infection - this can potentially worsen the infection by providing iron to pathogens
2. Delaying iron therapy indefinitely - once infection resolves, iron therapy should be initiated if indicated
3. Confusing inflammation with infection - IV iron should be withheld during acute infection but not necessarily during inflammation 4
4. Overlooking oral iron as an alternative - consider oral iron during infection if iron supplementation is urgently needed

In conclusion, the evidence strongly supports withholding IV iron during active infection due to the increased risk of worsening infection and potential interference with antibiotic efficacy. Treatment should focus on resolving the infection first, followed by appropriate iron supplementation once the infection has cleared.