Skip to main content

Advertisement

Log in

Three months of weekly rifapentine plus isoniazid for latent tuberculosis treatment in solid organ transplant candidates

  • Original Paper
  • Published:
Infection Aims and scope Submit manuscript

Abstract

Background

Isoniazid daily for 9 months is the recommended regimen for latent tuberculosis infection (LTBI) in solid organ transplant (SOT) candidates, but its use is controversial, due to reports of hepatotoxicity and low treatment completion rates. A 12-week course of once weekly directly observed therapy (DOT) with isoniazid plus rifapentine (3HP) is a new LTBI treatment regimen. Tolerability and safety data of 3HP LTBI treatment in SOT candidates are limited.

Methods

Twelve consecutive SOT candidates who underwent DOT with 3HP for LTBI at Westchester Medical Center, Valhalla, New York, USA, between January 2013 and August 2016 were prospectively evaluated for tolerability and safety of 3HP. The diagnosis of LTBI was made in a person with a positive interferon-gamma release test, without a history of previously treated active or latent tuberculosis infection, and without signs, symptoms, or radiographic evidence of active tuberculosis. Patients were followed up 1 month after treatment completion and at routine follow-up visits with their transplant providers.

Results

Eleven patients were men, and the median age was 60 years (range 44–72). Eight patients were liver, and four kidney transplant candidates. The median Model for End-Stage Liver Disease (MELD score) was 17 (range 10–31). All patients completed treatment. Only a single patient developed transaminitis greater than twice the baseline value. Three patients underwent liver transplantation. None of them developed tuberculosis at 9, 22, or 40 months following transplantation.

Conclusion

Directly observed 3HP LTBI treatment was not associated with hepatotoxicity, even in patients with higher MELD scores. Further studies are needed to confirm the safety and efficacy of this LTBI treatment regimen in the SOT population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Singh N, Paterson DL. Mycobacterium tuberculosis infection in solid-organ transplant recipients: impact and implications for management. Clin Infect Dis. 1998;27:1266–77.

    Article  CAS  PubMed  Google Scholar 

  2. Klote MM, Agodoa LY, Abbott K. Mycobacterium tuberculosis infection incidence in hospitalized renal transplant patients in the United States, 1998–2000. Am J Transplant. 2004;4:1523–8.

    Article  PubMed  Google Scholar 

  3. Torre-Cisneros J, Doblas A, Aguado JM, et al. Tuberculosis after solid-organ transplant: incidence, risk factors, and clinical characteristics in the RESITRA (Spanish Network of Infection in Transplantation) cohort. Clin Infect Dis. 2009;48:1657–65.

    Article  PubMed  Google Scholar 

  4. Subramanian AK, Morris MI, AST Infectious Diseases Community of Practice. Mycobacterium tuberculosis infections in solid organ transplantation. Am J Transplant. 2013;13:68–76.

    Article  CAS  PubMed  Google Scholar 

  5. Stucchi RS, Boin IF, Angerami RN, Zanaga L, Ataide EC, Udo EY. Is isoniazid safe for liver transplant candidates with latent tuberculosis? Transplant Proc. 2012;44:2406–10.

    Article  CAS  PubMed  Google Scholar 

  6. Grim SA, Layden JE, Roth P, et al. Latent tuberculosis in kidney and liver transplant patients: a review of treatment practices and outcomes. Transpl Infect Dis. 2015;17:768–77.

    Article  CAS  PubMed  Google Scholar 

  7. de Lemos AS, Vieira MA, Halpern M, et al. Results of implementation of preventive recommendations for tuberculosis after renal transplantation in an endemic area. Am J Transplant. 2013;13:3230–5.

    Article  PubMed  Google Scholar 

  8. Naqvi R, Akhtar S, Noor H, et al. Efficacy of isoniazid prophylaxis in renal allograft recipients. Transplant Proc. 2006;38:2057–8.

    Article  CAS  PubMed  Google Scholar 

  9. Sidhu A, Verma G, Humar A, Kumar D. Outcome of latent tuberculosis infection in solid organ transplant recipients over a 10-year period. Transplantation. 2014;98:671–5.

    Article  PubMed  Google Scholar 

  10. Fabrega E, Sampedro B, Cabezas J, et al. Chemoprophylaxis with isoniazid in liver transplant recipients. Liver Transplant. 2012;18:1110–7.

    Article  Google Scholar 

  11. Jafri SM, Singal AG, Kaul D, Fontana RJ. Detection and management of latent tuberculosis in liver transplant patients. Liver Transplant. 2011;17:306–14.

    Article  Google Scholar 

  12. Jahng AW, Tran T, Bui L, Joyner JL. Safety of treatment of latent tuberculosis infection in compensated cirrhotic patients during transplant candidacy period. Transplantation. 2007;83:1557–62.

    Article  CAS  PubMed  Google Scholar 

  13. Schluger LK, Sheiner PA, Jonas M, et al. Isoniazid hepatotoxicity after orthotopic liver transplantation. Mt Sinai J Med. 1996;63:364–9.

    CAS  PubMed  Google Scholar 

  14. Holty JE, Gould MK, Meinke L, Keeffe EB, Ruoss SJ. Tuberculosis in liver transplant recipients: a systematic review and meta-analysis of individual patient data. Liver Transplant. 2009;15:894–906.

    Article  Google Scholar 

  15. Saukkonen JJ, Cohn DL, Jasmer RM, Schenker S, Jereb JA, et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med. 2006;174:935–52.

    Article  CAS  PubMed  Google Scholar 

  16. Bliven-Sizemore EE, Sterling TR, Shang N, et al. Three months of weekly rifapentine plus isoniazid is less hepatotoxic than nine months of daily isoniazid for LTBI. Int J Tuberc Lung Dis. 2015;19:1039–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sterling TR, Villarino ME, Borisov AS, et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011;365:2155–66.

    Article  CAS  PubMed  Google Scholar 

  18. Martinson NA, Barnes GL, Moulton LH, et al. New regimens to prevent tuberculosis in adults with HIV infection. N Engl J Med. 2011;365:11–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. De Castilla DL, Rakita RM, Spitters CE, et al. Short-course isoniazid plus rifapentine directly observed therapy for latent tuberculosis in solid-organ transplant candidates. Transplantation. 2014;97:206–11.

    Article  PubMed  Google Scholar 

  20. Centers for Disease Control and Prevention (CDC). Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent Mycobacterium tuberculosis infection. MMWR Morb Mortal Wkly Rep. 2011;60:1650–3.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to B. M. Knoll.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Knoll, B.M., Nog, R., Wu, Y. et al. Three months of weekly rifapentine plus isoniazid for latent tuberculosis treatment in solid organ transplant candidates. Infection 45, 335–339 (2017). https://doi.org/10.1007/s15010-017-1004-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s15010-017-1004-5

Keywords

Navigation