What are the risks of using antibiotics with Remicade (Infliximab)?

Risks of Antibiotics with Infliximab (Remicade)

Patients treated with infliximab (Remicade) are at increased risk for serious infections when combined with antibiotics, particularly when other immunosuppressive agents are used concurrently. 1

Infection Risk with Infliximab

General Infection Risk

• Infliximab alone increases the risk of opportunistic infections due to its TNF-inhibiting properties 2
• The FDA black box warning specifically highlights the increased risk of serious infections that may lead to hospitalization or death 1
• Most patients who develop serious infections while on infliximab are taking concomitant immunosuppressants such as methotrexate or corticosteroids 1

Types of Infections Associated with Infliximab

1. Bacterial infections:

   • Increased risk of serious bacterial infections requiring hospitalization
   • Includes infections due to opportunistic pathogens like Legionella and Listeria 1

2. Mycobacterial infections:

   • Reactivation of latent tuberculosis
   • Often presents with extrapulmonary or disseminated disease 2
   • Risk appears higher with monoclonal antibodies like infliximab compared to other TNF inhibitors 2

3. Fungal infections:

   • Invasive fungal infections including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis 1
   • Patients may present with disseminated rather than localized disease

4. Viral infections:

   • Increased risk of viral infections, particularly with combination therapy 2
   • Includes risk of reactivation of hepatitis B 2

5. Clostridioides difficile infection:

   • Increased risk, especially when combined with corticosteroids 3

Combination Therapy Risks

Infliximab + Antibiotics

• The combination of infliximab with antibiotics requires careful monitoring due to the immunosuppressive effects of infliximab 1
• Antibiotics may disrupt gut microbiota, which could potentially affect disease activity in inflammatory bowel disease patients 2

Infliximab + Other Immunosuppressants

• Combination of infliximab with other immunosuppressive agents significantly increases infection risk:
  • Infliximab + immunosuppressant: 19% increased risk compared to infliximab alone 4
  • Infliximab + corticosteroid: 64% increased risk compared to infliximab alone 4
  • Infliximab + immunosuppressant + corticosteroid: 35% increased risk 4

Risk Factors for Serious Infections

• Combination therapy: Multiple immunosuppressive drugs significantly increase risk 2
• Age: Patients >65 years have up to 20-fold increased risk of severe infections 2
• Disease activity: Higher disease activity increases infection risk (each 100-point increase in CDAI associated with 30% increased risk) 2
• Nutritional status: Both malnutrition and obesity increase risk 2
• Comorbidities: Presence of other medical conditions increases risk 2, 1

Management Recommendations

1. Before starting antibiotics in patients on infliximab:

   • Assess infection risk factors
   • Consider temporarily withholding infliximab for febrile illness requiring antibiotics 2
   • Resume infliximab after resolution of symptoms and completion of antibiotic course 2

2. During concurrent treatment:

   • Closely monitor for signs and symptoms of infection
   • Discontinue infliximab if patient develops serious infection or sepsis 1
   • Consider empiric anti-fungal therapy in patients who develop severe systemic illness 1

3. Special considerations:

   • Test for latent tuberculosis before and during infliximab therapy 1
   • Consider prophylaxis against Pneumocystis pneumonia in high-risk patients 2
   • Be vigilant for atypical presentations of infections, as they are common in immunosuppressed patients 2

Common Pitfalls to Avoid

1. Failing to recognize infections early: Symptoms may be subtle or atypical in immunosuppressed patients
2. Overlooking drug interactions: Some antibiotics may interact with other medications the patient is taking
3. Continuing infliximab during active infection: Infliximab should be discontinued if serious infection develops 1
4. Inadequate monitoring: Regular follow-up is essential during concurrent therapy
5. Ignoring risk factors: Patients with multiple risk factors require closer monitoring

By understanding these risks and following appropriate management strategies, the potential complications of combining antibiotics with infliximab can be minimized while maintaining effective treatment of the underlying condition.