tacrolimus and Tuberculosis

Immunosuppressive drugs lead to an enhanced risk for infection. The impact of these drugs on the immune system can be broad (eg, corticosteroids) or targeted (eg, rituximab). Infections can have serious consequences, particularly if there is a delay in diagnosis. It is hoped that a knowledge of the type of immune defects that are induced by these drugs and the specific infections that have been reported will guide clinicians in the appropriate use of prophylactic regimens and diagnostic considerations in the event of pneumonia.

Topics: Aspergillosis; Communicable Diseases; Cyclosporine; Glucocorticoids; Humans; Immunosuppressive Agents; Lung Diseases; Methotrexate; Pneumonia, Pneumocystis; Purine Nucleosides; Tacrolimus; Tuberculosis; Tumor Necrosis Factor-alpha

Tuberculosis is a challenge in organ transplantation due to the interaction between Anti- Tuberculosis Treatment (ATT) and immunosuppressive drugs, such as Tacrolimus (TAC). This study aimed to assess this interaction and discuss the guidelines used in this specific case.. A retrospective, observational, single-center analysis was performed at the Department of Clinical Pharmacology (National Centre of Pharmacovigilance, Tunisia). We analyzed the database of patients who received TAC from 2009 until 2018. We included samples provided from renal transplant patients infected by Mycobacterium tuberculosis after transplantation. Trough blood levels (C0) were determined using an immunoassay analyzer. The Therapeutic Range (TR) of TAC was considered between 5 and 10 ng/mL. Pharmacokinetic parameters were compared between the period of co-administration of TAC/ATT (period A) and the period during which patients received only TAC (period B).. Seven renal transplant patients treated by TAC were included. 41 samples were analyzed (16; period A, 25; period B). Only 6 % of C0 values were found within TR during period A, while this rate was 44% during period B. During period A, 88% of TAC C0 was under the lower limit of TR, indicating a high risk of transplant rejection. The mean C0 and C0/D were significantly lower during period A (3.11±1.53 ng/mL vs 7.11 ± 3.37 ng/mL; p = 0.001 and 33.06 ± 24.89 vs 83.14 ± 44.46; p = 0.0006, respectively), without difference in doses between periods.. Considering the results of this study, clinicians are suggested to monitor TAC closely in this particular circumstance.

Topics: Drug Monitoring; Humans; Immunosuppressive Agents; Kidney Transplantation; Retrospective Studies; Tacrolimus; Tuberculosis

Little is known about the change in drug level and the need for dose adjustment of calcineurin inhibitor when it is used with rifabutin in solid organ transplant (SOT) recipients. We aimed to analyze whether the drug level of tacrolimus significantly reduced after the use of rifabutin and to assess optimal adjustment of tacrolimus dose in SOT recipients.. Of the SOT recipients in a tertiary referral center in South Korea in 2000-2019, 50 patients who maintained an unchanged dose of tacrolimus after the use of rifabutin for treating mycobacterial disease were enrolled. Their medical records were reviewed retrospectively.. The mean age of the patients was 53.9 ± 11.5 years. The most commonly transplanted organ was the liver (66.0%). The most common indication of rifabutin use was for treating active tuberculosis (78.0%). After rifabutin initiation, the trough level of tacrolimus decreased significantly to the subtherapeutic range in 38 (76.0%) patients. The drug levels of these 38 patients dropped from 7.2 to 3.8 ng/ml (p < .001) after rifabutin treatment. In these patients, the median 1.5-fold increase in the tacrolimus dose was required to restore the drug level to the within-therapeutic range.. These findings indicate that careful tacrolimus drug-level monitoring and dose adjustment are necessary for most SOT recipients when rifabutin is administered for the treatment of mycobacterial disease.

Topics: Adult; Aged; Humans; Immunosuppressive Agents; Middle Aged; Organ Transplantation; Retrospective Studies; Rifabutin; Tacrolimus; Transplant Recipients; 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

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 purpose of this study was to investigate the incidence, risk factors, and treatment outcome of tuberculosis (TB) in solid organ transplant (SOT) recipients treated with rifampicin.. The incidence density of TB was calculated by a retrospective cohort study. Risk factors for TB were analyzed by a nested case-control study. Treatment outcome and effects of anti-TB drugs on immunosuppressants and allograft were compared between patients whose initial 2-month intensive regimen included rifampicin and those whose intensive regimen did not.. Among the 2144 SOT recipients over 16 years, 40 cases of TB were found (1.7%). The incidence density was 372 cases per 10(5) patient years (95% confidence interval [CI], 270-503), which was 4 times higher than for the general Korean population (90 cases per 10(5) person years). The median time to the development of TB was 234 days (range, 33-3940 days). The use of tacrolimus (odds ratio [OR] 4.90; 95% CI, 1.74-13.80; P = 0.003) and cytomegalovirus (CMV) infection within the prior 3 months (OR 4.62; 95% CI, 1.44-14.87; P = 0.01) were found to be risk factors for TB. Patients whose intensive regimen included rifampicin were more likely to have an increased dose of calcineurin inhibitors than patients whose intensive regimen did not include rifampicin (13/15 [86.7%] vs. 3/14 [21.4%], P = 0.001). Graft rejection and mortality did not differ between the 2 groups.. Use of tacrolimus and CMV infection were major risk factors for TB in SOT recipients. The graft outcome and mortality did not differ whether rifampicin was used or not during the first 2-month intensive phase.

Topics: Adult; Aged; Antitubercular Agents; Case-Control Studies; Drug Interactions; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Organ Transplantation; Rifampin; Risk Factors; Tacrolimus; Treatment Outcome; Tuberculosis; Young Adult

: Taiwan is an area with moderate to high incidence of Mycobacterium tuberculosis infection. The risk of M tuberculosis infection in transplantation recipients is considered to be significant. Our aim in this study was to investigate the clinical spectrums of M tuberculosis-infected transplantation recipients in a southeast Asian country, Taiwan.. : We retrospectively analyzed the demographic data, clinical features, treatment, and outcome of M tuberculosis infection in kidney, heart, and liver transplant recipients from May 1996 to April 2005 at the National Taiwan University Hospital.. : Fifteen patients who had received solid organ transplantation developed tuberculosis (kidney = 6, heart = 7, liver = 2). The median duration from transplantation to diagnosis of tuberculosis was 31 months. The cumulative incidence of post-transplantation tuberculosis was 2.0% (15/760), ie, approximately 3 times that of the general population. Ten patients (66.7%) had pulmonary tuberculosis, 1 (6.7%) had extrapulmonary tuberculosis, and 4 (26.7%) had disseminated tuberculosis. Nine patients completed the anti-tuberculosis treatment; the median treatment duration was 12 months (pulmonary: 9 months; extrapulmonary: 13.5 months). No treatment failure was noted in patients receiving the complete treatment course. The graft failure and mortality rates of post-transplantation tuberculosis were 13.3% each (2/15). The tuberculosis-associated mortality rate was 6.7% (1/15).. : Cumulative incidence of tuberculosis was slightly higher in transplant recipients than in the general population in Taiwan. Conventional 4-combined anti-tuberculosis regimen for 12 months can treat the potentially fatal infection successfully in post-transplantation tuberculosis patients without recurrence.

Topics: Adult; Aged; Antitubercular Agents; Child; Cyclosporine; Female; Graft Rejection; Health Status; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycobacterium tuberculosis; Opportunistic Infections; Organ Transplantation; Tacrolimus; Treatment Outcome; Tuberculosis

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

Exclusion of occult diseases in the donor organ and prevention of infectious disease transmission are minimal requirements in organ transplantation. We report here a case of hepatic graft tuberculosis, which was most likely transmitted by the graft from the living-related donor. The course of the recipient included tuberculosis, rejection, and other infections, which led to vanishing bile duct syndrome. Due to various infections and tuberculosis, as well as a strong interaction between rifampicin and tacrolimus, the patient died of pneumonia on day 273 after transplantation. This case emphasizes the importance of care in the selection of a living-related donor for liver transplantation.

Topics: Adult; Drug Interactions; Fatal Outcome; Female; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Infant; Liver Diseases; Liver Function Tests; Liver Transplantation; Living Donors; Mothers; Postoperative Complications; Rifampin; Tacrolimus; Tuberculosis

Topics: Adult; Antibiotics, Antitubercular; Drug Interactions; Ethambutol; Female; Histocompatibility Testing; Humans; Immunosuppressive Agents; Infant; Isoniazid; Liver Transplantation; Living Donors; Mycobacterium tuberculosis; Postoperative Complications; Rifampin; Streptomycin; Tacrolimus; Tuberculosis