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Successful Bilateral Lung Transplantation From a Deceased Donor With Active Mycobacterium Tuberculosis Infection
Successful Bilateral Lung Transplantation From a Deceased Donor With Active Mycobacterium Tuberculosis Infection Imran Yaqoob Nizami, MD, Basha J. Khan, MD, Waleed Saleh, MD, and Mohamed Hussein, MD Organ Transplant Center and Department of Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; and Department of Cardiothoracic Surgery, Ain Shams University, Cairo, Egypt
In the present report, we describe a case wherein a Mycobacterium tuberculosis infection developed in the recipient after successful bilateral lung transplantation because of a solitary pulmonary nodule in the donor. (Ann Thorac Surg 2014;97:e109–10) Ó 2014 by The Society of Thoracic Surgeons Fig 1. Multinucleated giant cells (hematoxylin and eosin, 400).
R
ecipients of organ transplants are at an increased risk of infection not only because of their immunosuppressed state but also because they are susceptible to infections from organisms that may be transferred through the donor organs [1, 2]. Mycobacterium tuberculosis (MTB) is an important pathogen in lung transplant recipients, particularly in populations with a relatively high prevalence of MTB infection. The incidence of active MTB infection in transplant recipients varies worldwide, from 0.3% to 15%, depending on the region studied [2]. Only a few reports in the literature have provided definite evidence of donor-to-recipient transmission of MTB [2, 3]. The patient was a 14-year-old girl with rapidly deteriorating type 2 respiratory failure secondary to idiopathic bronchiectasis. She was receiving long-term oxygen therapy and noninvasive ventilation. A sputum culture yielded negative results for MTB; moreover, the result of the tuberculin skin test was negative. After her case was discussed during the multidisciplinary lung transplantation meeting, she was placed on the active lung transplantation waiting list. We identified a deceased donor for bilateral lung transplantation. The donor was a previously healthy 51-year-old Filipino man with no known history of lung disease or MTB infection. The cause of death of the donor was intracerebral hemorrhage. No information on the results of the tuberculin skin test for the donor was available. His family resided in the Philippines. Chest radiography performed before organ procurement indicated left lower lobe atelectasis. A bronchoscopy performed before lung procurement indicated the presence of scant mucoid secretions. Bronchoalveolar lavage (BAL) did not show any microorganisms on Gram staining and acid-fast bacilli (AFB)
staining. In the operating room, lung assessment indicated normal lung parenchyma with good lung compliance. However, on palpation, a solitary nodule, approximately 2 2 cm, was detected on the middle lobe. A wedge excision was performed, and the excised specimen was sent for frozen section. Histologic analysis of the nodule indicated a granuloma with caseation and necrosis but no evidence of malignancy (Figs 1, 2). The entire specimen was accidentally placed in formalin and could not be used for culture. Because of the patient’s critical medical status, the shortage of donor organs, and the fact that no other abnormal findings were detected in the lungs by direct visualization and palpation, the lung transplantation team decided to proceed with bilateral lung transplantation. The family was informed of the high risk and agreed to proceed with the transplantation. Bilateral sequential
Accepted for publication Nov 25, 2013. Address correspondence to Dr Khan, Organ Transplant Center, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia; e-mail: [email protected].
Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc
Fig 2. Extensive central necrosis (hematoxylin and eosin, 200). 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2013.11.077
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CASE REPORT NIZAMI ET AL LUNG Tx FROM DONOR WITH ACTIVE TB INFECTION
lung transplantation was successfully performed, and the patient’s postoperative course was uneventful. Strict infection prevention and post–MTB exposure Saudi guidelines were followed. Subsequently, the previously excised specimen was examined for the presence of AFB, and AFB staining yielded positive results. Moreover, the findings of a probe assay confirmed the presence of the MTB complex DNA (BDProbeTec, Becton Dickinson, Franklin Lakes, NJ). BAL culture from the right lung on the fifth postoperative day yielded negative results for AFB staining but showed positive results for the presence of the MTB complex DNA through DNA amplification (BDProbeTec); the MTB grown on subsequent culturing were found to be sensitive to all first-line antituberculosis drugs. However, BAL culture from the left lung showed negative results for AFB staining, quantitative bacterial culture, and the MTB complex DNA assay. The patient was given treatment with isoniazid, ethambutol, pyrazinamide, and moxifloxacin on the first postoperative day. After 5 days, another BAL culture from both lungs yielded negative results for AFB staining and the MTB complex DNA assay. However, the patient experienced an episode of grade A2 acute cellular rejection 2 weeks after transplantation and was treated with intravenous methylprednisolone (7 mg/kg) for 3 days. The patient was discharged 3 weeks after operation. The patient underwent a 12-month regimen of antituberculosis therapy, involving treatment with four drugs (isoniazid, ethambutol, pyrazinamide, and moxifloxacin) for the initial 2 months, followed by treatment with isoniazid, ethambutol, and moxifloxacin for 10 months. In addition, she received the standard triple immunosuppression regimen consisting of tacrolimus, mycophenolate mofetil, and corticosteroids. She underwent multiple surveillance bronchoscopies and biopsies, which indicated negative results for AFB staining and culturing. Her outcome at medium term is excellent, with Bronchiolitis obliterans syndrome 0 and no evidence of MTB recurrence 2.5 years after transplantation. The only other organ procured from the same donor was liver. The liver transplant team was informed of the diagnosis of tuberculosis in the lung transplant recipient. At the time of submitting this report, the liver recipient is doing well without any evidence of MTB infection.
Comment In the present report, we describe a case of pulmonary MTB infection in an individual who received a lung transplant from an infected donor. The presence of a caseating granuloma in the donor lung at the time of organ procurement indicated that infection by MTB was the most likely diagnosis. Although the shortage of lung donors is noted worldwide, this shortage is even more pronounced in Saudi Arabia. After discussion with the family, the lung transplantation team took the risk of transplanting the lungs, and achieved a favorable outcome.
Ann Thorac Surg 2014;97:e109–10
MTB infections in patients after transplantation are not uncommon. Previous studies in several countries have indicated that the rates of such infections can be as high as 15% in areas with a high prevalence of MTB infection [2]. Although nontuberculous mycobacterial infections are more frequently reported in lung transplant recipients, the incidence of MTB infection remains higher in these individuals than among the general population [4–6]. Among all solid organ transplant recipients, the lung transplant recipients carry the highest risk of MTB infection, particularly during the first year after transplantation [4]. However, only a few reports in the literature have provided definite evidence of the transmission of MTB infection from the donor to the recipient [2, 3]. MTB infection in lung transplant patients is associated with a significantly high morbidity and mortality [4, 5]. The crude mortality rate in cases of MTB infection after transplantation is 20% to 30% [6], whereas one Spanish study reported an attributable mortality of 10% (4). The treatment of MTB infection with rifampicin-based regimens is controversial because of their complex interactions with immunosuppressive medications. Rifampicin is a strong inducer of cytochrome P450, and it decreases the concentration of calcineurin inhibitors, which form the backbone of immunosuppressive regimens, to subtherapeutic levels. However, in the present case, we treated the patient with moxifloxacin instead of rifampicin and achieved excellent tolerability and eradication of infection. To our knowledge, this is the first report of a case of successful bilateral lung transplantation, wherein the donor was highly suspected of harboring an MTB infection at the time of organ procurement. The other two case reports identified donors as the potential source of transmission of MTB several days after the transplantation was performed [2, 3]. We believe that early initiation of antituberculosis therapy, the localized nature of the infection, and omission of induction therapy may have contributed to the successful outcome in the present case.
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. 2. Winthrop KL, Kubak BM, Pegues DA, et al. Transmission of mycobacterium tuberculosis via lung transplantation. Am J Transplant 2004;4:1529–33. 3. 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;153:1166–8. 4. 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. 5. Malouf MA, Glanville AR. The spectrum of mycobacterial infection after lung transplantation. Am J Respir Critic Care Med 1999;160:1611–6. 6. Subramanian AK, Morris MI. Mycobacterium tuberculosis infections in solid organ transplantation. Am J Transplant 2013;13:68–76.
In the present report, we describe a case wherein a Mycobacterium tuberculosis infection developed in the recipient after successful bilateral lung transplantation because of a solitary pulmonary nodule in the donor. (Ann Thorac Surg 2014;97:e109–10) Ó 2014 by The Society of Thoracic Surgeons Fig 1. Multinucleated giant cells (hematoxylin and eosin, 400).
R
ecipients of organ transplants are at an increased risk of infection not only because of their immunosuppressed state but also because they are susceptible to infections from organisms that may be transferred through the donor organs [1, 2]. Mycobacterium tuberculosis (MTB) is an important pathogen in lung transplant recipients, particularly in populations with a relatively high prevalence of MTB infection. The incidence of active MTB infection in transplant recipients varies worldwide, from 0.3% to 15%, depending on the region studied [2]. Only a few reports in the literature have provided definite evidence of donor-to-recipient transmission of MTB [2, 3]. The patient was a 14-year-old girl with rapidly deteriorating type 2 respiratory failure secondary to idiopathic bronchiectasis. She was receiving long-term oxygen therapy and noninvasive ventilation. A sputum culture yielded negative results for MTB; moreover, the result of the tuberculin skin test was negative. After her case was discussed during the multidisciplinary lung transplantation meeting, she was placed on the active lung transplantation waiting list. We identified a deceased donor for bilateral lung transplantation. The donor was a previously healthy 51-year-old Filipino man with no known history of lung disease or MTB infection. The cause of death of the donor was intracerebral hemorrhage. No information on the results of the tuberculin skin test for the donor was available. His family resided in the Philippines. Chest radiography performed before organ procurement indicated left lower lobe atelectasis. A bronchoscopy performed before lung procurement indicated the presence of scant mucoid secretions. Bronchoalveolar lavage (BAL) did not show any microorganisms on Gram staining and acid-fast bacilli (AFB)
staining. In the operating room, lung assessment indicated normal lung parenchyma with good lung compliance. However, on palpation, a solitary nodule, approximately 2 2 cm, was detected on the middle lobe. A wedge excision was performed, and the excised specimen was sent for frozen section. Histologic analysis of the nodule indicated a granuloma with caseation and necrosis but no evidence of malignancy (Figs 1, 2). The entire specimen was accidentally placed in formalin and could not be used for culture. Because of the patient’s critical medical status, the shortage of donor organs, and the fact that no other abnormal findings were detected in the lungs by direct visualization and palpation, the lung transplantation team decided to proceed with bilateral lung transplantation. The family was informed of the high risk and agreed to proceed with the transplantation. Bilateral sequential
Accepted for publication Nov 25, 2013. Address correspondence to Dr Khan, Organ Transplant Center, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia; e-mail: [email protected].
Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc
Fig 2. Extensive central necrosis (hematoxylin and eosin, 200). 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2013.11.077
e110
CASE REPORT NIZAMI ET AL LUNG Tx FROM DONOR WITH ACTIVE TB INFECTION
lung transplantation was successfully performed, and the patient’s postoperative course was uneventful. Strict infection prevention and post–MTB exposure Saudi guidelines were followed. Subsequently, the previously excised specimen was examined for the presence of AFB, and AFB staining yielded positive results. Moreover, the findings of a probe assay confirmed the presence of the MTB complex DNA (BDProbeTec, Becton Dickinson, Franklin Lakes, NJ). BAL culture from the right lung on the fifth postoperative day yielded negative results for AFB staining but showed positive results for the presence of the MTB complex DNA through DNA amplification (BDProbeTec); the MTB grown on subsequent culturing were found to be sensitive to all first-line antituberculosis drugs. However, BAL culture from the left lung showed negative results for AFB staining, quantitative bacterial culture, and the MTB complex DNA assay. The patient was given treatment with isoniazid, ethambutol, pyrazinamide, and moxifloxacin on the first postoperative day. After 5 days, another BAL culture from both lungs yielded negative results for AFB staining and the MTB complex DNA assay. However, the patient experienced an episode of grade A2 acute cellular rejection 2 weeks after transplantation and was treated with intravenous methylprednisolone (7 mg/kg) for 3 days. The patient was discharged 3 weeks after operation. The patient underwent a 12-month regimen of antituberculosis therapy, involving treatment with four drugs (isoniazid, ethambutol, pyrazinamide, and moxifloxacin) for the initial 2 months, followed by treatment with isoniazid, ethambutol, and moxifloxacin for 10 months. In addition, she received the standard triple immunosuppression regimen consisting of tacrolimus, mycophenolate mofetil, and corticosteroids. She underwent multiple surveillance bronchoscopies and biopsies, which indicated negative results for AFB staining and culturing. Her outcome at medium term is excellent, with Bronchiolitis obliterans syndrome 0 and no evidence of MTB recurrence 2.5 years after transplantation. The only other organ procured from the same donor was liver. The liver transplant team was informed of the diagnosis of tuberculosis in the lung transplant recipient. At the time of submitting this report, the liver recipient is doing well without any evidence of MTB infection.
Comment In the present report, we describe a case of pulmonary MTB infection in an individual who received a lung transplant from an infected donor. The presence of a caseating granuloma in the donor lung at the time of organ procurement indicated that infection by MTB was the most likely diagnosis. Although the shortage of lung donors is noted worldwide, this shortage is even more pronounced in Saudi Arabia. After discussion with the family, the lung transplantation team took the risk of transplanting the lungs, and achieved a favorable outcome.
Ann Thorac Surg 2014;97:e109–10
MTB infections in patients after transplantation are not uncommon. Previous studies in several countries have indicated that the rates of such infections can be as high as 15% in areas with a high prevalence of MTB infection [2]. Although nontuberculous mycobacterial infections are more frequently reported in lung transplant recipients, the incidence of MTB infection remains higher in these individuals than among the general population [4–6]. Among all solid organ transplant recipients, the lung transplant recipients carry the highest risk of MTB infection, particularly during the first year after transplantation [4]. However, only a few reports in the literature have provided definite evidence of the transmission of MTB infection from the donor to the recipient [2, 3]. MTB infection in lung transplant patients is associated with a significantly high morbidity and mortality [4, 5]. The crude mortality rate in cases of MTB infection after transplantation is 20% to 30% [6], whereas one Spanish study reported an attributable mortality of 10% (4). The treatment of MTB infection with rifampicin-based regimens is controversial because of their complex interactions with immunosuppressive medications. Rifampicin is a strong inducer of cytochrome P450, and it decreases the concentration of calcineurin inhibitors, which form the backbone of immunosuppressive regimens, to subtherapeutic levels. However, in the present case, we treated the patient with moxifloxacin instead of rifampicin and achieved excellent tolerability and eradication of infection. To our knowledge, this is the first report of a case of successful bilateral lung transplantation, wherein the donor was highly suspected of harboring an MTB infection at the time of organ procurement. The other two case reports identified donors as the potential source of transmission of MTB several days after the transplantation was performed [2, 3]. We believe that early initiation of antituberculosis therapy, the localized nature of the infection, and omission of induction therapy may have contributed to the successful outcome in the present case.
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. 2. Winthrop KL, Kubak BM, Pegues DA, et al. Transmission of mycobacterium tuberculosis via lung transplantation. Am J Transplant 2004;4:1529–33. 3. 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;153:1166–8. 4. 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. 5. Malouf MA, Glanville AR. The spectrum of mycobacterial infection after lung transplantation. Am J Respir Critic Care Med 1999;160:1611–6. 6. Subramanian AK, Morris MI. Mycobacterium tuberculosis infections in solid organ transplantation. Am J Transplant 2013;13:68–76.