Should tacrolimus (FK506) be held in a transplant patient with an infection?

From the Guidelines

The decision to hold tacrolimus in a transplant patient with infection should be made on a case-by-case basis, but generally, tacrolimus is not automatically discontinued during infections, as stated in the general principle that an active infection from the recipient must be ruled out before the start of immunosuppression 1. When managing a transplant patient with an infection, it is crucial to balance the risk of infection with the risk of organ rejection.

• For most mild to moderate infections, tacrolimus should be continued while treating the infection appropriately, with close monitoring of tacrolimus levels and adjustment of the dose as needed.
• However, dose reduction may be necessary, especially if the patient has elevated tacrolimus levels or if there are drug interactions with antimicrobial agents.
• For severe infections, particularly sepsis or life-threatening infections, temporary reduction of immunosuppression may be warranted, with tacrolimus dose reduction rather than complete discontinuation when possible, as complete discontinuation of tacrolimus carries significant risk of organ rejection and should only be considered in extreme circumstances under close transplant specialist supervision. The goal is to balance infection control with prevention of rejection, maintaining tacrolimus trough levels at the lower end of the therapeutic range during the infection period, and more frequent monitoring of tacrolimus levels is essential (every 2-3 days initially) as many antimicrobials, particularly azole antifungals and certain macrolides, can significantly increase tacrolimus levels 1. It's also worth noting that, the study from 2004 1 provides information about the diabetogenicity of tacrolimus, but this is not directly relevant to the decision of holding tacrolimus in a transplant patient with infection. Therefore, the focus should be on the study from 2014 1 which provides more relevant information for this specific scenario.

From the FDA Drug Label

Serious Infections [see Warnings and Precautions (5.2)] The FDA drug label does not answer the question.

From the Research

Infection Management in Transplant Patients

• The management of immunosuppression during infection in organ recipients is largely based on clinical experience, as few studies address the adjustment of immunosuppression during active infections 2.
• Infection remains a common complication in solid organ transplant recipients due to the regimens required to prevent rejection 3.
• The "net state of immune suppression" is a conceptual framework of all factors contributing to infectious risk, and assays that measure immune function in the immunosuppressed transplant recipient relative to infectious risk and allograft function are lacking 2.

Tacrolimus and Infection Risk

• There is evidence that newer, more potent immunosuppressive regimens, such as those including tacrolimus, may increase the risk of opportunistic infections, even in the presence of "adequate" antimicrobial preventive measures 4.
• The use of tacrolimus with mycophenolate mofetil has been associated with an increased risk of bacterial infection and prolonged neutrophil engraftment 5.

Immunosuppression Adjustment

• The prevention, diagnosis, and management of infectious disease in transplantation are major contributors to improved outcomes in organ transplantation, and every effort must be made to establish specific microbiologic diagnoses to optimize therapy 6.
• The role of infection in the stimulation of alloimmune responses awaits further definition, and major hurdles include the shifting worldwide epidemiology of infections, increasing antimicrobial resistance, and suboptimal assays for the microbiologic screening of organ donors 6.