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Published in: Infection 3/2017

01-06-2017 | Original Paper

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

Authors: B. M. Knoll, R. Nog, Y. Wu, A. Dhand

Published in: Infection | Issue 3/2017

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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.
Literature
1.
go back to reference Singh N, Paterson DL. Mycobacterium tuberculosis infection in solid-organ transplant recipients: impact and implications for management. Clin Infect Dis. 1998;27:1266–77.CrossRefPubMed Singh N, Paterson DL. Mycobacterium tuberculosis infection in solid-organ transplant recipients: impact and implications for management. Clin Infect Dis. 1998;27:1266–77.CrossRefPubMed
2.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
3.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
4.
go back to reference Subramanian AK, Morris MI, AST Infectious Diseases Community of Practice. Mycobacterium tuberculosis infections in solid organ transplantation. Am J Transplant. 2013;13:68–76.CrossRefPubMed Subramanian AK, Morris MI, AST Infectious Diseases Community of Practice. Mycobacterium tuberculosis infections in solid organ transplantation. Am J Transplant. 2013;13:68–76.CrossRefPubMed
5.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
6.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
7.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
8.
go back to reference Naqvi R, Akhtar S, Noor H, et al. Efficacy of isoniazid prophylaxis in renal allograft recipients. Transplant Proc. 2006;38:2057–8.CrossRefPubMed Naqvi R, Akhtar S, Noor H, et al. Efficacy of isoniazid prophylaxis in renal allograft recipients. Transplant Proc. 2006;38:2057–8.CrossRefPubMed
9.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
10.
go back to reference Fabrega E, Sampedro B, Cabezas J, et al. Chemoprophylaxis with isoniazid in liver transplant recipients. Liver Transplant. 2012;18:1110–7.CrossRef Fabrega E, Sampedro B, Cabezas J, et al. Chemoprophylaxis with isoniazid in liver transplant recipients. Liver Transplant. 2012;18:1110–7.CrossRef
11.
go back to reference Jafri SM, Singal AG, Kaul D, Fontana RJ. Detection and management of latent tuberculosis in liver transplant patients. Liver Transplant. 2011;17:306–14.CrossRef Jafri SM, Singal AG, Kaul D, Fontana RJ. Detection and management of latent tuberculosis in liver transplant patients. Liver Transplant. 2011;17:306–14.CrossRef
12.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
13.
go back to reference Schluger LK, Sheiner PA, Jonas M, et al. Isoniazid hepatotoxicity after orthotopic liver transplantation. Mt Sinai J Med. 1996;63:364–9.PubMed Schluger LK, Sheiner PA, Jonas M, et al. Isoniazid hepatotoxicity after orthotopic liver transplantation. Mt Sinai J Med. 1996;63:364–9.PubMed
14.
go back to reference 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.CrossRef 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.CrossRef
15.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
16.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
17.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
18.
19.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
20.
go back to reference 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. 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.
Metadata
Title
Three months of weekly rifapentine plus isoniazid for latent tuberculosis treatment in solid organ transplant candidates
Authors
B. M. Knoll
R. Nog
Y. Wu
A. Dhand
Publication date
01-06-2017
Publisher
Springer Berlin Heidelberg
Published in
Infection / Issue 3/2017
Print ISSN: 0300-8126
Electronic ISSN: 1439-0973
DOI
https://doi.org/10.1007/s15010-017-1004-5

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