Begin typing your search above and press return to search.
EPUB Before Print

FULL TEXT

ARTICLE
Successful Use of Rifamycin-Sparing Regimens for the Treatment of Active Tuberculosis in Lung Transplant Recipients

Objectives: Tuberculosis is an important opportunist infection that can complicate the posttransplant course of solid-organ transplant recipients. Lung transplant recipients are at higher risk of tuberculosis after transplant than are other solid-organ transplant recipients. Significant drug-drug interactions between antituberculous medications, especially rifampin, and immunosuppressant medications render treatment in this patient population especially challenging. Data on the management of tuberculosis in lung transplant recipients with rifamycin-sparing regimens are so far limited. Therefore, we evaluated the incidence, clinical features, treatment, and outcomes of active tuberculosis in lung transplant patients from a single center in Riyadh, Saudi Arabia.

Materials and Methods: Cases of active tuberculosis in lung transplant recipients diagnosed between January 2005 and December 2017 at our center were included. Data on patient demographics, clinical presentations, diagnosis, treatment regimens, and outcomes were collected.

Results: Seven of 133 lung transplant recipients (5.3%) were diagnosed with active tuberculosis during the study period, corresponding to an incidence rate of 2147/100 000 person-years. Patients were diagnosed at median time of 94 days posttransplant. Fever and weight loss were the most common presenting symptoms. All patients were initially treated with a regimen consisting of isoniazid, ethambutol, pyrazinamide, and moxifloxacin. Isoniazid was later substituted with rifabutin in 2 patients with isoniazid-resistant tuberculosis. All patients were treated for a total of 9 to 12 months, without any adverse event-related interruptions. All patients were alive at 12 months after the diagnosis of tuberculosis. There was no evidence of relapse in any of the patients after a median of 32 (range, 9-51) months of follow-up after treatment.

Conclusions: Rifamycin-sparing regimens appear to be safe and highly efficacious in the treatment of active tuberculosis in lung transplant recipients.


Key words : Donor-derived, Mycobacterium tuberculosis, Rifabutin, Rifampin

Introduction

Tuberculosis continues to be a significant challenge among solid-organ transplant (SOT) recipients. Active disease is mainly the result of the reactivation of a preexisting latent tuberculosis infection or is acquired through infected grafts.1 The overall rate of tuber­culosis in SOT recipients is approximately 2.4%; however, the rate may be considerably greater in areas with a high incidence of tuberculosis.2,3 Compared with that for other SOT grafts, lung transplant is associated with a 5.6-fold increase in the risk of active tuberculosis.4,5 In addition to the risk of the transmission of the infection, tuberculosis in SOT is associated with an increased risk of graft loss and death.6,7 Furthermore, the treatment of tuberculosis in SOT recipients is associated with an increased risk of drug toxicities and significant drug-drug interactions.8

Triple immunosuppression regimens that include a calcineurin inhibitor (eg, tacrolimus), an antipro­liferative agent (eg, mycophenolate mofetil [MMF]), and a corticosteroid are widely considered as standards of care for lung transplant recipients.9 Rifamycins are inducers of cytochrome P450, especially CYP3A, leading to a reduced bioavailability of coadministered medications that are metabolized through this system.10 Rifampin is an especially potent inducer of CYP3A, and its coadministration with immune suppressant drugs in SOT recipients has been reported as associated with acute rejection and graft loss.8 However, there are limited published data on the outcomes of lung transplant recipients treated for active tuberculosis, especially for those treated with rifamycin-sparing regimens. Herein, we evaluated the incidence, clinical features, treatment, and outcomes of active tuberculosis in lung transplant patients from a single center in Riyadh, Saudi Arabia.

Materials and Methods

Lung transplant recipients who were diagnosed with active tuberculosis between January 1, 2005 and December 30, 2017 were identified using the transplant database at King Faisal Specialist Hospital and Research Centre. Data on patient demographics, comorbidities, immunosuppressant medications, rejection episodes, time to tuberculosis diagnosis, micro­biological results, tuberculosis treatment regimens, and outcomes were collected. After lung transplant, recipients underwent surveillance bronchoscopy at 2, 4, 6, 12, 24, and 48 weeks. Bronc­hoalveolar lavage (BAL) fluid was obtained at all of these time points and tested for cell counts, Gram staining, bacterial cultures, fungal staining and culture, acid-fast bacilli (AFB) staining, mycobacterial cultures, and Mycobacterium tuberculosis nuclear acid am­plification test. The study was approved by our Institution’s Review Board. Informed consent was waived because of the retrospective nature of the study.

Statistical analyses
Continuous data are summarized as median and interquartile range. Categorical data are reported as frequencies. The incidence rate per person-year was calculated using the number of incident cases divided by the sum of the years of follow-up from the date of transplant. Follow-up was censored on December 30, 2017, diagnosis of tuberculosis, or death, whichever occurred first.11

Results

During the study period, 133 patients underwent lung transplant. Seven recipients (5.3%) were diagnosed with active tuberculosis, corresponding to an incidence rate of 2147 per 100 000 person-years. Most patients were male (57%), and the median age was 44 years (interquartile range, 31-48.5 years) (Table 1). Interstitial lung disease was the most common underlying indication for lung transplant (43%). The standard immunosuppression protocol consisted of methylprednisone and MMF for induction and tacrolimus, MMF, and prednisone for posttransplant maintenance. Only 1 patient (patient 2 in Table 1) had confirmed rejection episodes prior to the diagnosis of tuberculosis.

Unfortunately, detailed data on the donors’ exposure histories were not available. However, all 7 donors were from endemic areas for tuberculosis (India, Nepal, Bangladesh, Philippines, and Somalia). A pretransplant QuantiFERON-TB Gold (Qiagen, Germantown, MD, USA) test was negative in 6 recipients. One recipient (patient 6 in Table 1) had a positive result and was started on isoniazid after transplant. There were no documented pre- or posttransplant exposures to active tuberculosis in any of the 7 recipients.

Most patients (86%) were diagnosed within the first year posttransplant. The median time to tuberculosis diagnosis was 94 days (interquartile range, 65.5-103.8 days). The site of tuberculosis was the mediastinal lymph nodes in 1 patient, the pleura in 1 patient, and the lungs in 4 patients. One patient had multifocal disease involving the lungs, pleura, and mediastinal lymph nodes (Table 1).

Fever was the most common presenting symptom (83.3%), followed by weight loss and cough (42.9% each). None of the patients reported a history of hemoptysis. One patient (patient 3 in Table 1) was asymptomatic and was diagnosed when a routine BAL fluid test was positive for tuberculosis by polymerase chain reaction and culturing. Patient 7 received an allograft from a donor with known granulomatous pulmonary lesions. Tuberculosis in the donor was confirmed shortly after transplant, and antituberculous therapy was started. The details of this case were previously reported.12

Radiological abnormalities in 3 of the patients with pulmonary involvement included bilateral upper lobe changes. None of the patients had cavitary lesions. A mixture of ground-glass opacities, tree-in-bud appearances, and consolidation were observed in this series. All patients had radiological changes corresponding to the site of their tuber­culosis infection (Table 1). Tuberculosis was microbiologically confirmed in all 7 patients: by cultures and M. tuberculosis polymerase chain reaction (GeneXpert MTB/RIF, Cephid, Sunnyvale, CA, USA) in 6 patients and by AFB smears and a probe assay (BD ProbeTec, Becton Dickinson, Franklin Lakes, NJ, USA) in 1 patient. Sputum AFB smears were negative in all patients, whereas 3 patients had positive BAL fluid smears. Six patients (86%) underwent biopsies as part of the work-up. Histological findings are summarized in Table 1.

Isolates of M. tuberculosis from all but 2 patients were susceptible to isoniazid. All isolates were susceptible to rifampin, pyrazinamide, ethambutol, and moxifloxacin. All patients were initially treated with rifamycin-sparing regimens consisting of isoniazid, pyrazinamide, ethambutol, and moxiflo­xacin. Once susceptibility results were available, rifabutin was substituted for isoniazid in the 2 patients with isoniazid-monoresistant tuberculosis. None of the patients developed hepatotoxicity or any other complication that would lead to a modification or interruption of their antituberculous therapy. Patients were treated for a total duration of 9 to 12 months (Table 2).

All 7 patients achieved clinical and radiological cures, evident by the resolution of symptoms and/or radiological signs of infection. Microbiological clearance was documented in all 5 patients with pulmonary involvement. There was no evidence of relapse during the follow-up of 10 to 52 months after tuberculosis treatment completion. All patients were alive at 12 months after their diagnosis with active tuberculosis.

Discussion

The risk of tuberculosis after SOT is linked to the endemicity of tuberculosis in the general population. In areas of low endemicity (in which the tuberculosis rate in the general population ranges between 0 and 24 per 100 000 person-years), post-SOT tuberculosis rates are reported to range between 0.5% and 6.5%.7 From 1991 to 2010, the overall incidence rate of tuberculosis in Saudi Arabia declined from 14 to 17 per 100 000 person-years to around 10 per 100 000 person-years, according to the latest World Health Organization Global Tuberculosis Report.13,14

Intense immunosuppression after lung transplant is one of the major risk factors for the development of active tuberculosis. Lymphocyte-depleting agents are associated with higher rates of tuberculosis after SOT.5,7,15 However, none of our patients received a lymphocyte-depleting agent for induction immuno­sup­pression. One patient had several rejection episodes and received antithymocyte globulin for the treatment of rejection within 1 year before diagnosis of active tuberculosis.

Similar to that shown in previous reports, most patients in our series were diagnosed within the first 6 months of transplant (median of 94 days). Given the negative pretransplant interferon-gamma release assays in most of these patients, the early presen­tations suggest donor-derived tuberculosis.2 In June 2017, universal tuberculosis chemoprophylaxis with isoniazid for 6 months became policy at our center for all deceased donor allograft recipients. No cases of active tuberculosis have been diagnosed in lung transplant recipients since the implementation of this policy.

Our series included 2 patients with isoniazid-resistant tuberculosis (patients 3 and 6 in Tables 1 and 2). Both patients received grafts from donors from the Philippines, a country with high rates of drug-resistant tuberculosis.14 Our original intention was to use rifamycin-sparing regimens to avoid a potential drug-drug interaction with the calcineurin inhibitor.15-17 However, we substituted isoniazid with rifabutin in these 2 patients, once resistance to the former agent was reported. Multiple studies have demonstrated rifabutin as equally safe and effective as rifampin in the treatment of active tuberculosis in nontransplant settings.18 Compared with rifampin, rifabutin is a weaker inducer of CYP3A and, thus, has fewer drug-drug interactions.10 However, clinical experience with rifabutin in SOT-associated tuberculosis is limited.19,20 We identified 4 previous reports describing a total of 5 lung transplant recipients with active tuberculosis who were treated with rifabutin-based regimens.21-24 One report described a 73-year-old male patient who was diagnosed with pericardial tuberculosis at 4 months after lung transplant and who died within 1 month of starting a quadruple antituberculous regimen, in which rifampin was substituted with rifabutin.22 However, rifabutin-based antituberculous therapy was successful in the remaining 4 patients, 3 of whom had pulmonary disease and 1 of whom had tuberculosis of the oral cavity and colon.21,23,24 Rifabutin-based antituberculous therapy was suc­cessful in both patients in the present series, suggesting that this agent may be useful in the setting of lung transplant-associated tuberculosis.

Outside of SOT settings, rifamycin-sparing antituberculous regimens are usually used in the context of rifampin-resistant tuberculosis. In rifampin monoresistant tuberculosis, 12-month fluoroquinolone-based regimens have shown high success rates.25 More recently, shorter treatment regimens have also been recommended for multidrug-resistant pulmonary tuberculosis, subject to specific criteria.26 The shorter treatment regimen for multidrug-resistant tuberculosis comprises an intensive phase of kanamycin, moxifloxacin, pro­thiona­mide, clofazimine, pyrazinamide, high-dose isoniazid, and ethambutol for 4 to 6 months, followed by a 5-month continuation phase of moxifloxacin, clofazimine, ethambutol, and pyra­zina­mide. Extrapulmonary tuberculosis and risk of toxicity or drug-drug interactions are among the exclusion criteria for this short rifamycin-sparing antituberculous regimen.27 The complexity and critical importance of immune suppressive therapy in SOT recipients limit the utility of these shorter rifamycin-sparing approaches in the current setting.

Use of a rifamycin-sparing regimen for the treatment of lung transplant-associated tuberculosis has been previously reported (Table 3). In 2 cases, rifamycin resistance was the reason for use of a rifamycin-sparing regimen,28,29 whereas in the remaining 28 cases rifamycin was proactively omitted to avoid potential drug-drug interactions.4,24,28-35 The sites of tuberculosis in the 4 reported cases who died while on rifamycin-sparing antituberculous regimens were pulmonary (n = 2), disseminated (n = 1), and pericardial (n = 1).4,30,35 In the latter 2 cases, death occurred within 48 hours after start of antituberculous therapy.30,35 Among the 26 patients with successful outcomes with rifamycin-sparing antituberculous regimens for lung transplant-associated tuberculosis, the majority received triple or quadruple regimens containing isoniazid and a fluoroquinolone, and the treatment duration was 12 to 24 months.4,28,29,32-34 In our series, 5 patients, all with localized tuberculosis, were successfully treated with moxifloxacin and isoniazid-based regimens, without a rifamycin, for a total duration of 9 to 12 months. These outcomes suggest that such regimens may allow a shorter duration of treatment in lung transplant-associated tuberculosis.

Treatment recommendations for active tuberculosis in SOT recipients are based on data from nontransplant populations, case series, and expert opinions.2,19,20,36,37 The inclusion of a rifamycin in tuberculosis treatment regimens is generally considered highly desirable because of their rapid sterilizing activity, shorter treatment course, and association with high rates of treatment success.20,37,38 However, maximizing tuberculosis treatment efficacy needs to be balanced against the risk of graft rejection as a result of potential drug-drug interactions with rifampin. Current guidelines advocate the avoidance of rifampin in the treatment of localized, nonsevere forms of tuberculosis in SOT recipients. An allowance is made for using rifampin when necessary, but only with careful therapeutic drug monitoring of the immunosuppressant agents.19,20 Decisions need to be individualized based on the patient’s specific needs and the availability of ready access to therapeutic drug monitoring and logistical support, enabling a prompt clinical review and dose adjustments when required.

Conclusions

In our report on a series of patients with lung transplant-associated tuberculosis, excellent clinical response and completion of a tuberculosis treatment course were achieved without significant inter­ruption or serious adverse events. All patients survived for more than 1 year after the diagnosis of active tuberculosis. Notwithstanding the small size of the study, our experience supports the use of rifamycin-sparing regimens for the treatment of nonsevere forms of active tuberculosis in lung transplant recipients. The small number of included patients and lack of lung donor screening for tuberculosis are limitations of this study. However, as a result of this work, Saudi national policy was changed in November 2019 to require tuberculosis screening for all lung donors, using a combination of AFB staining and mycobacterial cultures of airway samples.


References:

  1. Sun HY. Treating tuberculosis in solid organ transplant recipients. Curr Opin Infect Dis. 2014;27(6):501-505. doi:10.1097/QCO.0000000000000102
    CrossRef - PubMed
  2. Abad CLR, Razonable RR. Mycobacterium tuberculosis after solid organ transplantation: A review of more than 2000 cases. Clin Transplant. 2018;32(6):e13259. doi:10.1111/ctr.13259
    CrossRef - PubMed
  3. Singh N, Paterson DL. Mycobacterium tuberculosis infection in solid-organ transplant recipients: impact and implications for management. Clin Infect Dis. 1998;27(5):1266-1277. doi:10.1086/514993
    CrossRef - PubMed
  4. Bravo C, Roldan J, Roman A, et al. Tuberculosis in lung transplant recipients. Transplantation. 2005;79(1):59-64. doi:10.1097/01.tp.0000147784.53188.dc
    CrossRef - PubMed
  5. 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(12):1657-1665. doi:10.1086/599035
    CrossRef - PubMed
  6. Aguado JM, Herrero JA, Gavalda J, et al. Clinical presentation and outcome of tuberculosis in kidney, liver, and heart transplant recipients in Spain. Spanish Transplantation Infection Study Group, GESITRA. Transplantation. 1997;63(9):1278-1286. doi:10.1097/00007890-199705150-00015
    CrossRef - PubMed
  7. Bumbacea D, Arend SM, Eyuboglu F, et al. The risk of tuberculosis in transplant candidates and recipients: a TBNET consensus statement. Eur Respir J. 2012;40(4):990-1013. doi:10.1183/09031936.00000712
    CrossRef - PubMed
  8. Sparkes T, Lemonovich TL, AST Infectious Diseases Community of Practice. Interactions between anti-infective agents and immunosuppressants-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13510. doi:10.1111/ctr.13510
    CrossRef - PubMed
  9. McDermott JK, Girgis RE. Individualizing immunosuppression in lung transplantation. Glob Cardiol Sci Pract. 2018;2018(1):5. doi:10.21542/gcsp.2018.5
    CrossRef - PubMed
  10. Burman WJ, Gallicano K, Peloquin C. Comparative pharmacokinetics and pharmacodynamics of the rifamycin antibacterials. Clin Pharmacokinet. 2001;40(5):327-341. doi:10.2165/00003088-200140050-00002
    CrossRef - PubMed
  11. U.S. Department of Health and Human Services. Principles of Epidemiology in Public Health Practice; 2006. https://www.cdc.gov/csels/dsepd/ss1978/SS1978.pdf

  12. Nizami IY, Khan BJ, Saleh W, Hussein M. Successful bilateral lung transplantation from a deceased donor with active Mycobacterium tuberculosis infection. Ann Thorac Surg. 2014;97(4):e109-110. doi:10.1016/j.athoracsur.2013.11.077
    CrossRef - PubMed
  13. Al-Orainey I, Alhedaithy MA, Alanazi AR, Barry MA, Almajid FM. Tuberculosis incidence trends in Saudi Arabia over 20 years: 1991-2010. Ann Thorac Med. 2013;8(3):148-152. doi:10.4103/1817-1737.114303
    CrossRef - PubMed
  14. World Health Organization. Global Tuberculosis Report; 2013.

  15. Aguado JM, Torre-Cisneros J, Fortun J, et al. Tuberculosis in solid-organ transplant recipients: consensus statement of the group for the study of infection in transplant recipients (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology. Clin Infect Dis. 2009;48(9):1276-1284. doi:10.1086/597590
    CrossRef - PubMed
  16. Hickey MD, Quan DJ, Chin‐Hong PV, Roberts JP. Use of rifabutin for the treatment of a latent tuberculosis infection in a patient after solid organ transplantation. Liver Transplant. 2013;19(4):457-461.
    CrossRef - PubMed
  17. Subramanian AK, Morris MI, AST Infectious Diseases Community of Practice. Mycobacterium tuberculosis infections in solid organ transplantation. Am J Transplant. 2013;13 Suppl 4:68-76. doi:10.1111/ajt.12100
    CrossRef - PubMed
  18. Davies G, Cerri S, Richeldi L. Rifabutin for treating pulmonary tuberculosis. Cochrane Database Syst Rev. 2007(4):CD005159. doi:10.1002/14651858.CD005159.pub2
    CrossRef - PubMed
  19. Santoro-Lopes G, Subramanian AK, Molina I, Aguado JM, Rabagliatti R, Len O. Tuberculosis Recommendations for Solid Organ Transplant Recipients and Donors. Transplantation. 2018;102(2S Suppl 2):S60-S65. doi:10.1097/TP.0000000000002014
    CrossRef - PubMed
  20. Subramanian AK, Theodoropoulos NM, Infectious Diseases Community of Practice of the American Society of Transplantation. Mycobacterium tuberculosis infections in solid organ transplantation: Guidelines from the infectious diseases community of practice of the American Society of Transplantation. Clin Transplant. 2019;33(9):e13513. doi:10.1111/ctr.13513
    CrossRef - PubMed
  21. Carswell JJ, Robbins MK. Mycobacterium tuberculosis infection of the mouth and lower gastrointestinal tract complicating lung transplantation. Chest. 2003;124(4):S256.
    CrossRef
  22. Makdisi G, Hooker R, Caldeira C. Pulmonary tuberculous and tuberculous pericardial tamponade post lung transplant. Ann Transl Med. 2017;5(15):308. doi:10.21037/atm.2017.04.43
    CrossRef - PubMed
  23. Malouf MA, Glanville AR. The spectrum of mycobacterial infection after lung transplantation. Am J Respir Crit Care Med. 1999;160(5 Pt 1):1611-1616. doi:10.1164/ajrccm.160.5.9808113
    CrossRef - PubMed
  24. Winthrop KL, Kubak BM, Pegues DA, et al. Transmission of mycobacterium tuberculosis via lung transplantation. Am J Transplant. 2004;4(9):1529-1533. doi:10.1111/j.1600-6143.2004.00536.x
    CrossRef - PubMed
  25. Park S, Jo KW, Lee SD, Kim WS, Shim TS. Treatment outcomes of rifampin-sparing treatment in patients with pulmonary tuberculosis with rifampin-mono-resistance or rifampin adverse events: A retrospective cohort analysis. Respir Med. 2017;131:43-48. doi:10.1016/j.rmed.2017.08.002
    CrossRef - PubMed
  26. Nunn AJ, Phillips PPJ, Meredith SK, et al. A trial of a shorter regimen for rifampin-resistant tuberculosis. N Engl J Med. 2019;380(13):1201-1213. doi:10.1056/NEJMoa1811867
    CrossRef - PubMed
  27. World Health Organization. Treatment Guidelines for Drug-Resistant Tuberculosis. Update; 2016.
    PubMed
  28. Lee J, Yew WW, Wong CF, Wong PC, Chiu CS. Multidrug-resistant tuberculosis in a lung transplant recipient. J Heart Lung Transplant. 2003;22(10):1168-1173. doi:10.1016/s1053-2498(02)01189-0
    CrossRef - PubMed
  29. Shitrit D, Bendayan D, Saute M, Kramer MR. Multidrug resistant tuberculosis following lung transplantation: treatment with pulmonary resection. Thorax. 2004;59(1):79-80.
    PubMed
  30. Miller RA, Lanza LA, Kline JN, Geist LJ. Mycobacterium tuberculosis in lung transplant recipients. Am J Respir Crit Care Med. 1995;152(1):374-376. doi:10.1164/ajrccm.152.1.7599848
    CrossRef - PubMed
  31. Morales P, Briones A, Torres JJ, Sole A, Perez D, Pastor A. Pulmonary tuberculosis in lung and heart-lung transplantation: fifteen years of experience in a single center in Spain. Transplant Proc. 2005;37(9):4050-4055. doi:10.1016/j.transproceed.2005.09.144
    CrossRef - PubMed
  32. Ridgeway AL, Warner GS, Phillips P, et al. Transmission of Mycobacterium tuberculosis to recipients of single lung transplants from the same donor. Am J Respir Crit Care Med. 1996;153(3):1166-1168. doi:10.1164/ajrccm.153.3.8630561
    CrossRef - PubMed
  33. Schulman LL, Scully B, McGregor CC, Austin JH. Pulmonary tuberculosis after lung transplantation. Chest. 1997;111(5):1459-1462. doi:10.1378/chest.111.5.1459
    CrossRef - PubMed
  34. Suzuki H, Matsuda Y, Noda M, et al. Management of de novo mycobacterial infection after lung transplantation without rifampicin: case series of a single institution. Transplant Proc. 2018;50(9):2764-2767.
    CrossRef - PubMed
  35. Boedefeld RL, Eby J, Boedefeld WM 2nd, et al. Fatal Mycobacterium tuberculosis infection in a lung transplant recipient. J Heart Lung Transplant. 2008;27(10):1176-1178. doi:10.1016/j.healun.2008.07.009
    CrossRef - PubMed
  36. Wagner GR, Osses JM, Caneva JO, Ahumada JR, Ibañez TP, Favaloro RR, Bertolotti AM. Incidence of tuberculosis post lung transplantation: single centre experience in Argentina. J Heart Lung Transplant. 2015;34(4):S309-310.
    CrossRef
  37. Meije Y, Piersimoni C, Torre-Cisneros J, et al. Mycobacterial infections in solid organ transplant recipients. Clin Microbiol Infect. 2014;20 Suppl 7:89-101. doi:10.1111/1469-0691.12641
    CrossRef - PubMed
  38. Munoz L, Santin M. Prevention and management of tuberculosis in transplant recipients: from guidelines to clinical practice. Transplantation. 2016;100(9):1840-1852. doi:10.1097/TP.0000000000001224
    CrossRef - PubMed
  39. Carlsen SE, Bergin CJ. Reactivation of tuberculosis in a donor lung after transplantation. AJR Am J Roentgenol. 1990;154(3):495-497. doi:10.2214/ajr.154.3.2106211
    CrossRef - PubMed
  40. Place S, Knoop C, Remmelink M, et al. Paradoxical worsening of tuberculosis in a heart-lung transplant recipient. Transpl Infect Dis. 2007;9(3):219-224. doi:10.1111/j.1399-3062.2006.00194.x
    CrossRef - PubMed
  41. Hiemann NE, Grimmer S, Kemper D, Knosalla C, Hetzer R. Tuberculous meningitis in a lung transplanted patient. Transpl Infect Dis. 2012;14(4):E19-22. doi:10.1111/j.1399-3062.2012.00736.x
    CrossRef - PubMed
  42. Mortensen E, Hellinger W, Keller C, et al. Three cases of donor-derived pulmonary tuberculosis in lung transplant recipients and review of 12 previously reported cases: opportunities for early diagnosis and prevention. Transpl Infect Dis. 2014;16(1):67-75. doi:10.1111/tid.12171
    CrossRef - PubMed
  43. Cassir N, Delacroix R, Gomez C, et al. Transplanted lungs and the "white plague": A case-report and review of the literature. Medicine (Baltimore). 2017;96(13):e6173. doi:10.1097/MD.0000000000006173
    CrossRef - PubMed


DOI : 10.6002/ect.2020.0277


PDF VIEW [126] KB.

From the 1Section of Infectious Diseases, Department of Medicine, King Faisal Specialist Hospital and Research Centre; the 2Section of Lung Transplant, Organ Transplant Center, King Faisal Specialist Hospital and Research Centre; and the 3Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; and the 4Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
Acknowledgements: The authors have not received any funding or grants in support of the presented research or for the preparation of this work and have no declarations of potential conflicts of interest.
Corresponding author: Reem S. Almaghrabi, Section of Infectious Diseases, Department of Medicine, King Faisal Specialist Hospital and Research Centre, 11211, PO Box 3354, MBC 46, Riyadh, Saudi Arabia
Phone: +966 11 4427494
E-mail: ramaghrabi@kfshrc.edu.sa