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Mycobacterial infection complicating renal transplantation
Mycobacterial Infection Complicating Renal Transplantation S.-L. Lui, K.P. Cheng, F.K. Li, C.Y. Lo, B.Y. Choy, W.K. Lo, T.M. Chan, and K.N. Lai
M
YCOBACTERIAL infection is an important complication of renal transplantation. However, the incidence of mycobacterial infection among renal transplant patients varies widely throughout the world.1–3 Moreover, the relative significance of mycobacterial tuberculosis (MTB) and non-tuberculous mycobacterial (NTM) infection has not been well described. This prompted us to carry out this study to determine the incidence and pattern of mycobacterial infection among renal transplant patients in our locality. MATERIALS AND METHODS The records of all renal transplant patients who were being followed in our center from January 1987 to December 1996 were retrospectively reviewed. These included 289 cadaveric and 92 living related transplants. The immunosuppressive regimen consisted of prednisolone, cyclosporine (CyA), and azathioprine. Patients with delayed graft function received antilymphocyte globulin for 10 to 14 days. Patients with history of tuberculosis before the transplantation were routinely given isoniazid prophylaxis for 1 year. The diagnosis of mycobacterial infection was based on (1) demonstration of mycobacteria on smear or culture; (2) demonstration of caseating granuloma on histologic examination; or (3) good response to therapeutic trial of anti-tuberculous treatment in patients with fever of unknown origin.
ating granuloma on transbronchial biopsy. Of the five patients with NTM infection, two had mycobacterium avium intracellulare, and one had mycobacterium cheloni infection of the lung. They presented with fever and pulmonary infiltrates on chest X-rays. All three patients had positive sputum smear for AFB, and their sputum culture subsequently grew the respective mycobacteria. The remaining two patients had mycobacterium marinum infection; they presented with tenosynovitis of the interphalangeal joints of the hand. The diagnosis was established by positive culture from the synovial biopsy materials. Patients with MTB were treated with isoniazid, rifampicin, along with pyrazinamide for the first 2 months. Eight patients also received ethambutol and/or ofloxacin. The total treatment duration ranged from 9 to 12 months. Patients with NTM were treated with clarithromycin, ethambutol, and rifampicin for 6 to 9 months. The antimycobacterial treatment was in general well tolerated. Five patients developed transient derangement of liver function, which resolved spontaneously without discontinuation of the medications. None of the patients died. No disease recurrence has been detected after a mean follow-up of 45 months (range 12 to 92 months). DISCUSSION
RESULTS
Twenty-four cases of mycobacterial infection were identified in 381 renal transplant patients (6.3%) over a 10-year period, of which 19 cases were due to MTB (80%) and 5 cases were due to NTM (20%). The mean age of the patients was 35.1 years (range 20 to 46 years) and the male-to-female ratio was 3.8:1. The diagnosis of mycobacterial infection was made within the first year of transplantation in 9 patients (37%), between 1 and 5 years in 8 patients (33%), and beyond 5 years in 7 patients (30%). In patients with MTB, 15 had pulmonary disease (79%), 2 had urinary tract disease (10.5%), and 2 had disseminated disease (10.5%). The most common presentation was fever unresponsive to antibiotic treatment. Chest x-ray findings in patients with pulmonary TB included pulmonary infiltrates (14), pleural effusion (4), and cavitation (1). The diagnosis was established by positive smear and culture for acid-fast bacilli (AFB) in 9 patients and positive culture alone in 8 patients. In 2 patients, the diagnosis was made by a good response to anti-tuberculous drugs. Two patients had case-
The incidence of mycobacterial infection among our renal transplant patients is substantially higher than that reported in North America (1%)1 or Europe (2%)2 but is not as high as that reported in India (10%).3 This difference is to be expected and reflects the difference in the overall incidence of mycobacterial infection in these countries. Sakhuja reported that nearly 60% of cases of tuberculosis was diagnosed within 1 year of transplantation.3 However, we found that nearly one-third of our cases were diagnosed beyond 5 years of transplantation, indicating that mycobacterial infection can occur years after transplantation when the immunosuppression has been reduced to a minimum. The exact incidence of NTM infection in renal transplant patients is unknown as most of the cases in the literature are From Division of Nephrology, University Department of Medicine, Queen Mary Hospital, Pokfulam, Hong Kong, China. Address reprint requests to Sing-Leung Lui, Division of Nephrology, Queen Mary Hospital, Department of Medicine, Pokfulam, Hong Kong, China.
© 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
0041-1345/98/$19.00 PII S0041-1345(98)0966-X
Transplantation Proceedings, 30, 3133–3134 (1998)
3133
3134
in case-report format. Twenty percent of the cases of mycobacterial infection in our patients were caused by NTM. The relatively high incidence of NTM infection in renal transplant patients is clinically significant as the management of such cases is different from those with MTB. The optimal therapeutic regimen for NTM infections has not been defined. Many NTM show in vitro resistance to isoniazid. Recently, it has been shown that combination therapy with clarithromycin, rifampicin, and ethambutol is effective against most NTM infections.4,5 We have employed a similar regimen in treating our patients with NTM infection with favorable results. We conclude that mycobacterial infection is an important complication of renal transplantation in our locality, with NTM infection accounting for a
LUI, CHENG, LI ET AL
substantial proportion of the cases. A high index of suspicion and early initiation of appropriate treatment are both essential for optimal management of mycobacterial infection complicating renal transplantation.
REFERENCES 1. Lloveras J, Peterson PK, Simmons RL, et al: Arch Intern Med 142:888, 1982 2. Higgins RM, Cahn AP, Porter D, et al: Q J Med 286:145, 1991 3. Sakhuja V, Jha V, Varma PP, et al: Transplantation 61:211, 1996 4. Griffith DE, Wallace RJ Jr: Semin Respir Infect 11:301, 1996 5. Sesin GP, Manzi SF, Pacheco R: Am J Health Syst Pharm 53:2585, 1996
M
YCOBACTERIAL infection is an important complication of renal transplantation. However, the incidence of mycobacterial infection among renal transplant patients varies widely throughout the world.1–3 Moreover, the relative significance of mycobacterial tuberculosis (MTB) and non-tuberculous mycobacterial (NTM) infection has not been well described. This prompted us to carry out this study to determine the incidence and pattern of mycobacterial infection among renal transplant patients in our locality. MATERIALS AND METHODS The records of all renal transplant patients who were being followed in our center from January 1987 to December 1996 were retrospectively reviewed. These included 289 cadaveric and 92 living related transplants. The immunosuppressive regimen consisted of prednisolone, cyclosporine (CyA), and azathioprine. Patients with delayed graft function received antilymphocyte globulin for 10 to 14 days. Patients with history of tuberculosis before the transplantation were routinely given isoniazid prophylaxis for 1 year. The diagnosis of mycobacterial infection was based on (1) demonstration of mycobacteria on smear or culture; (2) demonstration of caseating granuloma on histologic examination; or (3) good response to therapeutic trial of anti-tuberculous treatment in patients with fever of unknown origin.
ating granuloma on transbronchial biopsy. Of the five patients with NTM infection, two had mycobacterium avium intracellulare, and one had mycobacterium cheloni infection of the lung. They presented with fever and pulmonary infiltrates on chest X-rays. All three patients had positive sputum smear for AFB, and their sputum culture subsequently grew the respective mycobacteria. The remaining two patients had mycobacterium marinum infection; they presented with tenosynovitis of the interphalangeal joints of the hand. The diagnosis was established by positive culture from the synovial biopsy materials. Patients with MTB were treated with isoniazid, rifampicin, along with pyrazinamide for the first 2 months. Eight patients also received ethambutol and/or ofloxacin. The total treatment duration ranged from 9 to 12 months. Patients with NTM were treated with clarithromycin, ethambutol, and rifampicin for 6 to 9 months. The antimycobacterial treatment was in general well tolerated. Five patients developed transient derangement of liver function, which resolved spontaneously without discontinuation of the medications. None of the patients died. No disease recurrence has been detected after a mean follow-up of 45 months (range 12 to 92 months). DISCUSSION
RESULTS
Twenty-four cases of mycobacterial infection were identified in 381 renal transplant patients (6.3%) over a 10-year period, of which 19 cases were due to MTB (80%) and 5 cases were due to NTM (20%). The mean age of the patients was 35.1 years (range 20 to 46 years) and the male-to-female ratio was 3.8:1. The diagnosis of mycobacterial infection was made within the first year of transplantation in 9 patients (37%), between 1 and 5 years in 8 patients (33%), and beyond 5 years in 7 patients (30%). In patients with MTB, 15 had pulmonary disease (79%), 2 had urinary tract disease (10.5%), and 2 had disseminated disease (10.5%). The most common presentation was fever unresponsive to antibiotic treatment. Chest x-ray findings in patients with pulmonary TB included pulmonary infiltrates (14), pleural effusion (4), and cavitation (1). The diagnosis was established by positive smear and culture for acid-fast bacilli (AFB) in 9 patients and positive culture alone in 8 patients. In 2 patients, the diagnosis was made by a good response to anti-tuberculous drugs. Two patients had case-
The incidence of mycobacterial infection among our renal transplant patients is substantially higher than that reported in North America (1%)1 or Europe (2%)2 but is not as high as that reported in India (10%).3 This difference is to be expected and reflects the difference in the overall incidence of mycobacterial infection in these countries. Sakhuja reported that nearly 60% of cases of tuberculosis was diagnosed within 1 year of transplantation.3 However, we found that nearly one-third of our cases were diagnosed beyond 5 years of transplantation, indicating that mycobacterial infection can occur years after transplantation when the immunosuppression has been reduced to a minimum. The exact incidence of NTM infection in renal transplant patients is unknown as most of the cases in the literature are From Division of Nephrology, University Department of Medicine, Queen Mary Hospital, Pokfulam, Hong Kong, China. Address reprint requests to Sing-Leung Lui, Division of Nephrology, Queen Mary Hospital, Department of Medicine, Pokfulam, Hong Kong, China.
© 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
0041-1345/98/$19.00 PII S0041-1345(98)0966-X
Transplantation Proceedings, 30, 3133–3134 (1998)
3133
3134
in case-report format. Twenty percent of the cases of mycobacterial infection in our patients were caused by NTM. The relatively high incidence of NTM infection in renal transplant patients is clinically significant as the management of such cases is different from those with MTB. The optimal therapeutic regimen for NTM infections has not been defined. Many NTM show in vitro resistance to isoniazid. Recently, it has been shown that combination therapy with clarithromycin, rifampicin, and ethambutol is effective against most NTM infections.4,5 We have employed a similar regimen in treating our patients with NTM infection with favorable results. We conclude that mycobacterial infection is an important complication of renal transplantation in our locality, with NTM infection accounting for a
LUI, CHENG, LI ET AL
substantial proportion of the cases. A high index of suspicion and early initiation of appropriate treatment are both essential for optimal management of mycobacterial infection complicating renal transplantation.
REFERENCES 1. Lloveras J, Peterson PK, Simmons RL, et al: Arch Intern Med 142:888, 1982 2. Higgins RM, Cahn AP, Porter D, et al: Q J Med 286:145, 1991 3. Sakhuja V, Jha V, Varma PP, et al: Transplantation 61:211, 1996 4. Griffith DE, Wallace RJ Jr: Semin Respir Infect 11:301, 1996 5. Sesin GP, Manzi SF, Pacheco R: Am J Health Syst Pharm 53:2585, 1996