mycophenolic-acid and Tuberculosis

Patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at high risk of acquiring tuberculosis (TB) due to a status of immunosuppression. We conducted a nested case control study to investigate the incidence and risk factors for TB after allo-HSCT. Between 2012 and 2017, 730 consecutive allo-HSCT recipients were enrolled, and 14 patients (1.92%) were diagnosed with TB. Relatively, 54 allo-HSCT recipients were selected as control. Patients who suffered TB had a significantly higher 3-year non-relapse mortality rate than the control group (30.36% vs 5.39%, P < 0.01). In multivariate analysis, invasive fungal disease (HR 4.87, 95% CI 1.39-17.09), treatment with a relatively high dose of prednisone (HR 10.34, 95% CI 1.12-95.47) and treatment with tacrolimus (HR 4.79, 95% CI 1.18-19.44) were identified independent risk factors for TB occurrence post allo-HSCT (P < 0.05). Meanwhile, donor type, dose and type of anti-thymocyte globulin (ATG) administrated, as well as treatment intensity, did not alter the incidence of TB. Therefore, allo-HSCT recipients with unexplained fever, especially those who suffer from invasive fungal disease and ongoing immunosuppression with a relatively high dose of prednisone or tacrolimus, are at a high-risk of developing active TB. Closely Monitoring TB occurrence, making a timely diagnosis and administering the proper treatment may be beneficial to those high-risk patients.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Child; Disease Susceptibility; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Incidence; Invasive Fungal Infections; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Prednisone; Risk; Transplant Recipients; Tuberculosis; Young Adult

Tuberculosis (TB) mortality is high among kidney transplant (KT) recipients. Although local epidemiology is an important factor, diagnostic/therapeutic challenges and immunosuppressive therapy (ISS) may influence outcomes. We analyzed the cumulative incidence (CumI) of TB in KT recipients receiving a variety of ISS with long-term follow-up. Our retrospective single-center cohort study included all KT procedures performed between January 1, 1998, and August 31, 2014, with follow-up until August 31, 2014. Induction therapy was based on perceived immunological risk; maintenance ISS included prednisone and calcineurin inhibitor (CNI) plus azathioprine (AZA), and mycophenolic acid (MPA) or mechanistic target of rapamycin inhibitor (mTORi). Thirty-four patients received belatacept/MPA. KT was performed on 11 453 patients and followed for 1989 (IQR 932 to 3632) days. Among these, 152 patients were diagnosed with TB (CumI 1.32%). Median time from KT to TB was 18.8 (IQR 7.2 to 60) months, with 59% of patients diagnosed after the first year. Unadjusted analysis revealed an increasing confidence interval (CI) of TB (0.94% CNI/AZA vs 1.6% CNI/MPA [HR = 1.62, 95% CI = 1.13 to 2.34, P = .009] vs 2.85% CNI/mTORi [HR = 2.45, 95% CI = 1.49 to 4.32, P < .001] vs 14.7% belatacept/MPA [HR = 13.14, 95% CI = 5.27 to 32.79, P < .001]). Thirty-seven (24%) patients died, and 39 (25.6%) patients experienced graft loss. Cytomegalovirus infection (P = .02) and definitive ISS discontinuation (P < .001) were associated with death. Rejection (P = .018) and ISS discontinuation (P = .005) occurred with graft loss. TB occurred at any time after KT and was influenced by ISS.

Topics: Abatacept; Adult; Azathioprine; Calcineurin Inhibitors; Cytomegalovirus Infections; Female; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Risk; TOR Serine-Threonine Kinases; Treatment Outcome; Tuberculosis

To treat organ transplant patients with mycobacterial infection, physicians need to pay attention to interaction between drugs used against mycobacteria and immunosuppressants. The purpose of this report is to describe the clinical features of and treatment for mycobacterial infection in lung transplant (LTx) recipients.. To investigate the incidence, treatment, and outcome for mycobacterial infection, we retrospectively reviewed 100 LTx recipients in our program since 2000.. Four recipients (4.0%) developed mycobacterial infection. Three recipients took tacrolimus, and 1 received cyclosporine with mycophenolate mofetil and a steroid for immunosuppression. Tuberculosis (TB) was isolated from 2 recipients, and non-tuberculous mycobacteriosis (NTM) was detected in the other 2. We treated the patients with levofloxacin + isoniazid + pyrazinamide + ethambutol (EB) for TB and clarithromycin (CLM) + EB for NTM to avoid interaction of calcineurin inhibitors (CNI: 8-10 ng/mL in trough level) with rifampicin (RFP). In treating the patients with NTM, we were able to maintain an adequate blood concentration of CNI by decreasing the dosage from one-half to one-quarter. All mycobacterial infections were controlled with treatment. In 1 patient with chronic obstructive pulmonary disease (COPD) infected with TB in the native lung, the forced expiratory volume in 1 second (FEV1) unexpectedly increased from 1890 mL before infection to 2320 mL possibly due to organization of the native lung.. We were able to manage the mycobacterial infections using drugs other than RFP without any cases of acute rejection under adequate immunosuppression. Organization of the native lung with TB infection unexpectedly resulted in improvement of FEV1 in a COPD patient.

Topics: Adult; Anti-Bacterial Agents; Calcineurin Inhibitors; Cyclosporine; Drug Interactions; Drug Therapy, Combination; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Incidence; Lung Transplantation; Male; Middle Aged; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis; Mycophenolic Acid; Nontuberculous Mycobacteria; Postoperative Complications; Retrospective Studies; Rifampin; Tacrolimus; Tuberculosis

Tuberculosis (TB) is an important cause of morbidity and mortality in renal transplant recipients. Immunosuppressive drugs are one of the most important risk factor for post-transplant tuberculosis (PTTB). A paucity of data exists about the impact of the type of calcineurin inhibitor on PTTB.. In this retrospective study, all adult patients on calcineurin inhibitor-based immunosuppression were included. Patients receiving TB chemoprophylaxis were excluded. Diabetes, duration of dialysis, hepatitis B and C, past treated TB, induction therapy, type of antimetabolite, acute rejection, new onset of diabetes after renal transplantation (RT) (NODAT) and cytomegalovirus (CMV) were analyzed in tacrolimus (Tac) and cyclosporine (CsA) groups. Primary outcome was incidence of TB and secondary outcomes were timeline of development of TB after RT and pattern of TB in the two groups.. Of the 1664 patients included, 582 patients received CsA-based immunosuppression while 1082 received Tac-based immunosuppression. Duration of dialysis, positive tuberculin skin test, use of induction, mycophenolate mofetil use, CMV infection, and NODAT were significantly more, and hepatitis B infection, past treated TB, and acute rejection episodes were significantly less in the Tac group. At the end of follow-up, incidence of TB in the Tac group was significantly less than in the CsA group (6.1% vs 19.9%, P<.001). Mean time for development of TB after RT was similar in both the groups and nodal and disseminated TB were more common in the Tac group.. In conclusion, our study shows that use of Tac as compared to CsA significantly decreases incidence of PTTB. Time of infection since transplant was similar in both the groups. However, nodal and disseminated TB were more common in the Tac group.

Topics: Adolescent; Adult; Aged; Antibiotics, Antitubercular; Calcineurin Inhibitors; Child; Cyclosporine; Female; Follow-Up Studies; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Incidence; India; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Prospective Studies; Retrospective Studies; Tacrolimus; Tuberculosis; Young Adult

Topics: Adult; Female; Fever; Humans; Immunocompromised Host; Lupus Erythematosus, Systemic; Lupus Nephritis; Muscle, Skeletal; Mycophenolic Acid; Prednisone; Prognosis; Pyomyositis; Tuberculosis; Venous Thrombosis

Successful renal transplantation (RT) improves quality of life and patient survival. Advances in immunosuppressants for RT have improved the prevention and treatment of acute rejection as well as reduced the risk of chronic graft damage, but immunodeficiency may render patients vulnerable to opportunistic infections. We conducted this study to compare the difference in tuberculosis (TB) infection rates between a single institution and a national database of RT recipients in Taiwan. There were 153 patients with TB (3.2%) among 4,835 RT recipients in the database during the period 2000-2009, with a higher prevalence of men (P = .018) and diabetes patients (P = .029). In our institution's registry, 33 patients (2.7%) developed 35 episodes of TB infection among 1,209 RT recipients, but there were no significant differences in general characteristics among different subgroups. Interestingly, the use of cyclosporine was significantly more frequent in RT recipients with TB than in those without in both the national database and in our institution. In contrast, TB infection was negatively correlated with the use of tacrolimus (TAC) and mycophenolate (MPA). RT recipients with TB infection had poor survival (P = .0013) and low graft survival (P = .0003). Taken together, analyses of the national database and the RT patients in our institution revealed that the use of long-term cyclosporine-based immunosuppressive agents was associated with a greater risk of developing post-transplantation TB compared with that of other immunosuppressive agents, but the chronicity and accumulation effect of TAC and MPA should be observed despite the negative correlation found herein. In conclusion, post-transplantation TB is a serious health threat and one of the major causes of death among RT recipients, and a high index of suspicion to ensure early diagnosis and prompt initiation of treatment for TB is crucial. The use of optimal immunosuppressive agents to minimize acute rejection, monitoring of high-risk recipients, prompt diagnosis, and appropriate treatment are required to manage TB infection in endemic areas such as Taiwan.

Topics: Adult; Databases, Factual; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Risk Factors; Tacrolimus; Taiwan; Tuberculosis

The incidence of tuberculosis among patients with systemic rheumatic diseases is much higher than in the general population (the risk is multiplied by 5 to 15 in patients with systemic lupus erythematosus). Reactivation of a latent tuberculosis is frequent, as assessed by the short delay of occurrence after a systemic rheumatic disease has been diagnosed. Besides immunosuppression induced by the underlying disease, the role of glucocorticoids and of immunosuppressive therapy including biotherapies using TNF antagonists must be underlined. Tuberculosis in such patients frequently presents as extrapulmonary or disseminated disease. A screening of tuberculosis is recommended before anti-TNF therapy, and includes previous history questioning, chest X ray, tuberculin skin test with 5 international units of tuberculin. Immunological methods of tuberculosis detection are under evaluation in these patients. If a latent tuberculosis infection is diagnosed, a specific tuberculosis chemoprophylaxis, started at least 3 weeks before initiation of TNF antagonists, has allowed to reduce the occurrence of anti-TNF-associated tuberculosis in patients living in Europe and North America. The screening strategies for tuberculosis should probably be extended in all patients with systemic rheumatic diseases receiving glucocorticoids and/or immunosuppressive therapy.

Topics: Antibodies, Monoclonal; Antitubercular Agents; Cyclophosphamide; Cyclosporine; France; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Incidence; Japan; Mycophenolic Acid; Rheumatic Diseases; Risk Factors; Spain; Sweden; Tuberculin Test; Tuberculosis; Tumor Necrosis Factor-alpha; United States

Mycophenolate mofetil (MMF) and tacrolimus (TAC) are more potent than conventional immunosuppressive drugs, i.e. azathioprine, cyclosporin and prednisolone, and may be associated with an increase in the incidence of infections in the post-transplantation (post-tx) period. The aim of this study was to determine if the use of either or both of MMF and TAC for immunosuppression in renal transplant recipients increases the prevalence or modifies the clinical presentation of tuberculosis (TB), when compared with conventional therapy.. The medical records of 443 adult patients who received a kidney transplant between 1994 and 2002 were reviewed retrospectively. Comparisons were made between patients who had conventional immunosuppressive treatments (cyclosporin, azathioprine and prednisolone) or an alternative regimen (including MMF, TAC or both).. We found 20 patients (4.5%) to have post-tx TB. There were 13 cases of TB (age 38.9+/-10.6 years) among 328 patients who received conventional immunosuppressants (group I) (4.0%) and seven cases (age 24.2+/-7.4 years) among 115 (6.1%) who received an alternative immunosuppressive regimen (group II) (P>0.05). The patients in group II were younger than the patients in group I (P = 0.002). A significantly higher number of patients in group II developed TB within the first 6 months post-tx (P = 0.042). However, there was no significant difference between the two groups regarding clinical and radiographic presentations or outcomes.. Immunosuppression with TAC or MMF is associated with the development of TB earlier in the post-tx period and in younger patients.

Topics: Adult; Azathioprine; Cyclosporine; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Prednisolone; Retrospective Studies; Tacrolimus; Tuberculosis

We report the third case in the literature of a patient with a long-lasting renal allograft who experienced tuberculosis just after the switch from azathioprine to mycophenolate mofetil. The switch was likely responsible for the reactivation of dormant tuberculosis; prophylactic antituberculous treatment should be considered in cases of such a therapeutic change.

Topics: Antitubercular Agents; Azathioprine; Humans; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Treatment Outcome; Tuberculosis

Topics: Adult; Azathioprine; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Mycophenolic Acid; Postoperative Complications; Time Factors; Tuberculosis