Prevention and treatment of tuberculosis in solid organ transplant recipients

ABSTRACT

Introduction: Tuberculosis (TB) in solid organ transplant (SOT) recipients is associated with significant morbidity and mortality. Its management in transplant recipients is difficult and highly complex, given the underlying immunosuppression and the risks of drug–drug interactions imposed by immunosuppressive drugs that are needed to maintain the transplant allograft.

Areas covered: We provide a brief review of TB in SOT and discuss the clinical indications, mechanisms of action and drug resistance, drug–drug interactions, and adverse effects of anti-TB drugs. We provide a summary of recent clinical trials, which serve as the foundation for current recommendations. We further include relevant updates on new agents being evaluated for clinical use in TB management.

Expert commentary: TB causes significant morbidity in SOT recipients. The drugs used in the treatment for latent TB and active disease in SOT are similar to the regimens used in the general population. However, TB disease in transplant recipients is more difficult to manage because of the potential for hepatotoxicity and the complex drug–drug interactions with immunosuppressive drugs. We believe that alternative regimens suited for the vulnerable transplant population, and more therapeutic drug options are needed given the adverse toxicities associated with currently approved anti-TB drugs.

KEYWORDS:

• Mycobacterium tuberculosis
• solid organ transplant
• anti-TB drugs
• prevention
• treatment

Article Highlights

• In most regions, TB infrequently causes infection in SOT recipients but it can lead to significant morbidity and mortality due to the net state of immune suppression. TB in transplant can occur via transmission from the donor allograft, reactivation of latent TB, or through de novo infection.

• Reactivation TB most commonly occurs a year after transplant, and it often presents as extrapulmonary (affecting the allograft) or disseminated disease. Fever is most frequently the only symptom.

• Latent tuberculosis infection (LTBI) treatment is recommended among those at highest risk for TB reactivation. Isoniazid (INH or H) is currently the drug of choice, although other alternatives providing shorter duration and less hepatotoxicity, such as 3 months of isoniazid and Rifapentine (3HP) are under study.

• The treatment of active TB disease mirrors treatment in the general population with certain caveats: treatment is typically longer and more complex due to drug–drug interactions and the risk of hepatotoxicity.

• Multi-drug resistant TB is rare in transplantation.

• Novel drugs for treatment are needed and should include the provision of shorter regimens, greater efficacy, better side effect profiles, or fewer drug–drug interactions.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.