Can immunosuppressant medications, such as prednisone (corticosteroid), cyclosporine (calcineurin inhibitor), or tacrolimus (calcineurin inhibitor), increase the risk of bacterial infections?

Can Immunosuppressant Medications Cause Bacterial Infections?

Yes, immunosuppressant medications including prednisone, cyclosporine, and tacrolimus significantly increase the risk of bacterial infections, with the risk escalating dramatically when these agents are used in combination. 1

Mechanism and Risk Profile

Immunosuppressants compromise the immune system through various mechanisms, rendering patients vulnerable to bacterial, viral, fungal, and protozoal infections. 1 The FDA explicitly warns that corticosteroids like prednisone "suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens." 2 Similarly, tacrolimus and other calcineurin inhibitors place patients "at increased risk of developing bacterial, viral, fungal, and protozoal infections, including opportunistic infections" that may lead to fatal outcomes. 3

Specific Bacterial Infection Risks by Agent

Corticosteroids (Prednisone)

• Dose-dependent risk threshold: ≥20 mg/day of prednisone for ≥2 weeks represents high-risk dosing for opportunistic bacterial infections. 1, 4
• Even moderate doses (≥10 mg/day) increase the relative risk of all infectious events (RR 1.30), while any dose increases opportunistic infection risk (RR 1.67). 1, 4
• Corticosteroids are particularly associated with serious bacterial infections including Pseudomonas aeruginosa and postoperative infectious complications. 1, 4
• The infectious complication rate increases proportionally with corticosteroid dosage. 2

Calcineurin Inhibitors (Cyclosporine, Tacrolimus)

• Both agents carry substantial risk for bacterial infections, with tacrolimus showing increased rates of serious bacterial infections particularly in the first 6 months of treatment. 1
• Cyclosporine is associated with bacterial infections including pneumonia, with one study showing 69% of patients developed bacterial infections. 1
• The FDA mandates monitoring for infection development and warns these can be "severe and at times fatal." 3

Combination Therapy: Exponential Risk Amplification

The most critical clinical consideration is that combination immunosuppressive therapy dramatically amplifies infection risk beyond additive effects. 1

• Single immunosuppressive agent: OR 2.9 for opportunistic infections 1
• Two or three agents combined: OR 14.5 for opportunistic infections 1
• The combinations of thiopurines plus steroids, or thiopurines plus steroids plus anti-TNF agents present the greatest risk. 1

Additional Risk Factors That Compound Infection Risk

Patient-Specific Factors

• Age: Patients >65 years have up to 20-fold increased risk of severe infections (11% vs 0.5% in younger patients). 1
• Malnutrition: OR 2.31 for opportunistic infections 1
• Obesity: OR 1.07 per kg/m² increase in BMI 1
• Active underlying disease: Each 100-point increase in disease activity scores associated with 30% increased infection risk. 1
• Comorbidities: Diabetes, chronic diseases, and concomitant conditions amplify risk. 1

Treatment-Related Factors

• Recent antibiotic use (within 3 months) combined with corticosteroids further increases bacterial infection risk, particularly Pseudomonas. 4, 5
• Broad-spectrum antibiotic therapy for 7 days in the past month plus corticosteroids creates particularly high risk. 4, 5
• Perioperative corticosteroid use increases postoperative infectious complications. 1, 4

Clinical Monitoring and Prevention Algorithm

Pre-Treatment Assessment

• Screen for latent infections (tuberculosis, hepatitis B, Strongyloides) before initiating immunosuppression. 2, 6
• Document baseline complete blood count, renal function, and potassium levels. 1
• Assess vaccination status and update age-appropriate immunizations. 6

During Treatment Monitoring

• Monitor for infection development at every clinical encounter, maintaining high index of suspicion. 2, 3
• For corticosteroids: Check CBC, potassium, and renal function every 4-6 weeks. 1
• For tacrolimus/cyclosporine: Daily drug levels initially, then every 2-3 days until stable, then every 1-2 weeks for first 1-2 months, then every 1-2 months once stable. 1
• Adjust monitoring frequency when adding/removing medications that affect drug metabolism. 1

Prophylaxis Considerations

• Consider Pneumocystis jirovecii prophylaxis for prednisone ≥20 mg/day for ≥4 weeks. 5, 6
• Tuberculosis chemoprophylaxis for patients with latent TB or tuberculin reactivity during prolonged therapy. 2
• Individualized antimicrobial prophylaxis based on specific risk factors and exposures. 6

Critical Clinical Pitfalls

Masked Infection Presentation

Corticosteroids and other immunosuppressants can mask typical signs and symptoms of infection, making clinical assessment difficult. 2, 7 Maintain heightened vigilance even when classic inflammatory markers are absent.

Dose Reduction vs. Discontinuation

When infection develops, discontinuation of immunosuppressive agents is recommended. 6 For elevated serum creatinine with tacrolimus toxicity, consider dose reduction or temporary interruption. 3 Balance infection risk against rejection risk in transplant patients.

Stress Dosing After Discontinuation

Corticosteroid-induced adrenal suppression can persist up to 12 months after discontinuation. 5, 2 During any stress situation in this period (surgery, severe illness), reinstitute or increase corticosteroid dosing to prevent adrenal crisis.

Perioperative Management

Minimize or suspend corticosteroids before elective procedures when possible to reduce infectious complications. 4, 5 Any corticosteroid use at time of surgery increases postoperative infection risk. 4

Risk Stratification for Bacterial Infections

Low Risk:

• Single agent at low doses
• Prednisone <10 mg/day 4, 5
• Short treatment duration (<2 weeks)

Moderate Risk:

• Prednisone 10-19 mg/day 4, 5
• Single calcineurin inhibitor at therapeutic levels
• Age <50 years without comorbidities

High Risk:

• Prednisone ≥20 mg/day for ≥2 weeks 1, 4
• Combination immunosuppressive therapy 1
• Age >65 years 1
• Recent antibiotic use plus immunosuppression 4, 5
• Malnutrition or significant comorbidities 1

For high-risk patients, empirical coverage for Pseudomonas aeruginosa and other opportunistic bacterial pathogens should be strongly considered when respiratory or other serious infections develop. 4, 5