Should azathioprine be held in cases of bacteremia?

Should Azathioprine Be Held for Bacteremia?

Yes, azathioprine should be immediately discontinued upon recognition of bacteremia and held until the infection is completely resolved and the patient is clinically stable. 1

Rationale for Discontinuation

The Surviving Sepsis Campaign explicitly recommends immediate discontinuation of azathioprine upon recognition of sepsis, with initiation of appropriate sepsis management including blood cultures, broad-spectrum antimicrobials, and fluid resuscitation. 1 This recommendation prioritizes mortality reduction in the setting of serious bacterial infection.

Infection Risk with Azathioprine

Azathioprine significantly increases susceptibility to bacterial infections through multiple mechanisms:

• The drug causes immunosuppression even in the absence of neutropenia, with mild lymphopenia commonly occurring and contributing to infection risk. 1
• When combined with corticosteroids (common in inflammatory bowel disease and immunobullous disorders), azathioprine leads to markedly increased susceptibility to viral, bacterial, and fungal infections. 2
• Infection in elderly patients with bullous pemphigoid treated with azathioprine and prednisolone has been identified as a significant cause of mortality, particularly compared to prednisolone alone. 2

FDA Safety Information

The FDA drug label explicitly warns that patients receiving immunosuppressants including azathioprine are at increased risk for bacterial, viral, fungal, protozoal, and opportunistic infections, including reactivation of latent infections, which may lead to serious and fatal outcomes. 3

Clinical Management Algorithm

During Active Bacteremia:

1. Immediately discontinue azathioprine upon recognition of bacteremia 1
2. Obtain blood cultures and initiate broad-spectrum antimicrobials 1
3. Implement full sepsis management protocols including fluid resuscitation 1
4. Monitor complete blood counts closely, as bone marrow suppression may complicate infection management 4

Holding Period:

• Keep azathioprine discontinued until infection is completely resolved and patient is clinically stable 1
• For specific severe infections like varicella zoster, temporary withdrawal with prompt antiviral therapy is recommended 1

Restarting Azathioprine Post-Infection:

• When restarting azathioprine after infection resolution, monitor weekly complete blood counts and liver function tests for at least 4 weeks 1
• Return to the standard monitoring protocol of weekly FBC and LFTs for 4 weeks, then reduce to minimum of once every 3 months 2

Important Caveats

Infection can occur even with normal blood counts - azathioprine increases infection susceptibility through lymphopenia and immunosuppression independent of neutropenia, so normal complete blood counts do not rule out infection risk. 5 This is a critical pitfall, as clinicians may falsely reassure themselves with normal neutrophil counts while the patient remains immunocompromised.

Case reports document severe outcomes - published cases include fatal sepsis in pancytopenic patients 4, Bacillus cereus bacteremia requiring surgical intervention 6, and CMV-related haemophagocytic syndrome requiring azathioprine withdrawal and antiviral therapy. 7 These cases underscore that continuing azathioprine during active infection can lead to life-threatening complications.

Combination therapy amplifies risk - patients on azathioprine plus corticosteroids face substantially higher infection-related mortality than those on either agent alone, making discontinuation even more critical in this population. 2