What is the data surrounding IV iron administration during an active infection?

What is the data surrounding IV iron administration during an active infection?

Comment by InpharmD Researcher

While guidelines and hypotheses recommend holding IV iron during active infections to prevent supplementing the pathogens, retrospective observational studies suggest there is a low risk of significant harm with continuing IV iron.

Background

Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend considering temporarily holding iron therapy in patients with chronic kidney disease (CKD) while they have an active systemic infection. This is primarily because iron is essential for growth and proliferation of many bacteria, viruses, parasites, and helminths. Iron also has subtle effects on the immune system’s host response to microbes. Theoretical evidence suggests iron administration may worsen an existing infection, but clinical evidence is lacking. Briefly suspending iron therapy until the infection is cleared is unlikely to significantly affect the progress of iron replenishment or the correction of anemia. As such, IV iron is usually not administered when people have an active systemic infection. Clinical judgment is necessary with milder infections to balance the risks of continued use of IV iron versus delaying further iron administration until infection resolves. [1]

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

What is the data surrounding IV iron administration during an active infection?

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-2 for your response.

Intravenous Iron in Patients Hospitalized with Bacterial Infections: Utilization and Outcomes
Design	Retrospective chart review N= 197
Objective	To examine patterns of prescribing IV iron in patients hospitalized and treated for a bacterial infection, and their associated clinical outcomes
Study Groups	All patients (N= 197)
Inclusion Criteria	Patients aged 18 years and older who received both iron sucrose and antibiotics during the same admission at Maine Medical Center in 2019
Exclusion Criteria	Patients undergoing hemodialysis; receiving perioperative antibiotics, antibiotics for labor management, antibiotics for chronic prophylaxis, IV iron administered more than 8 days after antibiotic completion, or less than 24 hours of antibiotics; not admitted to the hospital or immunocompromised
Methods	This was a retrospective chart review of adult patients who received IV iron sucrose and antibiotics during the same admission at a single center in Maine. Data collected included iron studies, practices for prescribing IV iron, and clinical outcomes.
Outcome Measures	Mortality, readmission within 30 days of discharge
Baseline Characteristics		All patients (N= 197)
	Mean age, years	67.8 ± 15.7
	Male	52%
	Median length of stay, days	9
	Infection Respiratory Urinary tract infection Skin/soft tissue infection Abdominal/pelvic Bone/joint Bacteremia Endocarditis Sepsis (unspecified) Meningitis	32.9% 23.7% 14.4% 13.4% 4.8% 3.4% 3% 2.5% 0.5%
	Median duration of inpatient antibiotics, days (range)	5 (1-148)
	Antibiotic prescription before IV iron	54.5%
Results		All patients (n= 197)
	Mortality within 30 days of discharge	7.1%
	Readmission within 30 days	16.2%
	Blood transfusion needed	28.4%
	Fever after IV iron	1.6%
	Extended antibiotic therapy (longer than initial plan or guideline recommendations)	2.5%
	Broadened antibiotic therapy after IV iron	2%
Adverse Events	N/A
Study Author Conclusions	This study showed that when patients were administered IV iron in the setting of acute bacterial infection, most patients did not have negative outcomes. Future studies are needed to determine the risk of worsening infection in vulnerable clinical subgroups.
Critique	The study provides valuable insights into the safety of IV iron administration in patients with bacterial infections, but its retrospective design and lack of a comparator group limit the ability to draw causal conclusions. The study's findings may not be generalizable to all clinical subgroups, particularly those with severe infections or immunodeficiency. This is also only applicable to iron sucrose, as other IV iron may not have the same results.

References:

Centanni N, Hammond J, Carver J, Craig W, Nichols S. Intravenous Iron in Patients Hospitalized with Bacterial Infections: Utilization and Outcomes. J Maine Med Cent. 2024;6(2):1. doi:10.46804/2641-2225.1176

Receipt of Intravenous Iron and Clinical Outcomes among Hemodialysis Patients Hospitalized for Infection
Design	Retrospective, observational, cohort study N= 22,820
Objective	To examine the association between intravenous iron and clinical outcomes among hemodialysis patients hospitalized for infection
Study Groups	IV iron (n= 2,463) No IV iron (n= 20,357)
Inclusion Criteria	Adult Medicare beneficiaries on in-center hemodialysis who received intravenous iron in the 14 days preceding their first hospitalization for bacterial infection in 2010
Exclusion Criteria	Hospitalizations where admission and discharge dates were the same; patients lacking Medicare claims or billed dialysis sessions in 2010; missing covariate data
Methods	Data from the US Renal Data System was used. The primary exposure was receipt of intravenous iron from the day of hospital admission to discharge. Outcomes included all-cause 30-day mortality, mortality in 2010, length of hospital stay, and readmission for infection or death within 30 days of discharge. Multivariable analyses adjusted for demographics, comorbidities, and infected organ system
Duration	Data from January 1, 2010 to November 30, 2010
Outcome Measures	Primary: All-cause 30-day mortality, mortality in 2010 Secondary: Length of hospital stay, readmission for infection or death within 30 days of discharge
Baseline Characteristics		IV iron (n= 2,463)	No IV iron (n= 20,357)	p-value
	Age, years	63.0±14.7	62.7±14.9	0.42
	Duration of ESRD, years	3.3 (1.4–5.9)	3.1 (1.4–5.8)	0.44
	Male	51.0%	51.2%	0.87
	Race White Black Other	56.2% 39.9% 3.9%	57.1% 38.3% 4.6%	0.11
	Infection location Bacteremia Catheter Skin/soft tissue Gastrointestinal Respiratory Urinary Joint/bone	29.3% 32.9% 10.4% 8.1% 7.2% 7% 3%	30.8% 27% 11.2% 12% 6.9% 6.5% 2.9%	0.11 <0.001 0.25 <0.001 0.61 0.40 0.69
	Hematocrit	33.4±3.9	33.6±3.8	0.02
	Iron sucrose was the most frequently administered product (86.6% of patients who received intravenous iron), followed by ferric gluconate (12.4%), ferumoxytol (0.8%), and iron dextran (0.2%).
Results	30-day mortality (OR)	0.86 (0.74 to 1.00)		p=0.04
	Mortality (HR)	0.92 (0.85 to 1.00)		p=0.04
	Readmission for infection or death within 30 days (OR)	1.08 (0.96 to 1.22)		p=0.19
	There was a significant difference in length of stay (10.1 vs 10.5 days; p= 0.05); however, this may not be clinically significant.
	Subgroup analyses found a significant difference in mortality between iron sucrose versus no IV iron (OR, 0.84; 95% CI, 0.72 to 0.98; p= 0.03). No significant difference was observed between ferric gluconate and no IV iron nor ferric gluconate versus iron sucrose. Ferric gluconate had a significantly longer length of stay compared to iron sucrose (11.7 vs 9.8 days; p= 0.005).
Adverse Events	No specific adverse events related to intravenous iron were reported
Study Author Conclusions	This analysis does not support withholding intravenous iron upon admission for bacterial infection in hemodialysis patients, although clinical trials are required to make definitive recommendations.
Critique	The study's large sample size and focus on a specific clinical scenario are strengths. However, as an observational study based on databases, it is subject to residual confounding and lacks data on iron indices. The majority of intravenous iron was administered on the day of admission, limiting insights into longer-term use during hospitalization.

References:

Ishida JH, Marafino BJ, McCulloch CE, et al. Receipt of Intravenous Iron and Clinical Outcomes among Hemodialysis Patients Hospitalized for Infection. Clin J Am Soc Nephrol. 2015;10(10):1799-1805. doi:10.2215/CJN.01090115