tacrolimus and Opportunistic-Infections

Dematiaceous molds are increasingly recognized as important human pathogens. We report 2 cases of cutaneous phaeohyphomycosis in renal allograft recipients, caused by Alternaria alternata and Curvularia spp., respectively, which demonstrate the diversity in clinical presentation, the different therapeutic strategies, and the clinical importance of azole antifungal-induced drug-drug interactions with immunosuppressive therapy.

Topics: Aged; Alternaria; Antifungal Agents; Ascomycota; Azoles; Dermatomycoses; Drug Interactions; Drug Therapy, Combination; Female; Hand Dermatoses; Humans; Immunocompromised Host; Immunosuppression Therapy; Kidney Transplantation; Leg Dermatoses; Male; Middle Aged; Opportunistic Infections; Tacrolimus

Introduction of new innovative immunosuppressive strategies has been the milestone of the recent evolution of intestinal and multivisceral transplantation. With new insights into the mechanisms of organ engraftment and acquired tolerance, the Pittsburgh tolerogenic protocol was recently introduced and consisted of two main therapeutic principles: recipient pretreatment with lymphoid ablating antibodies and minimal post-transplant immunosuppression with tacrolimus monotherapy. The reported herein improved survival and the striking ability to wean immunosuppression among the intestinal and multivisceral recipients pretreated with a single-dose of Thymoglobulin (rATG) or Campath-1H (alemtuzumab) supports our working hypothesis with successful induction of variable tolerance. It is important, however, that careful monitoring of subtle histologic changes in serial endoscopic-guided mucosal biopsies be carried out for early diagnosis of allograft immune activation with prompt restoration of the baseline immunosuppressive therapy. Future scientific discoveries with better understanding of the mechanisms of immune tolerance and clinical introduction of reliable assays will increase the chance and safety of achieving complete tolerance among the intestinal and other solid organ recipients. This review will focus on the historic evolution of the immunosuppressive and other management strategies utilized for the intestinal and multivisceral recipients at the University of Pittsburgh with special reference to allograft immunity and the successful achievement of partial tolerance.

Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antilymphocyte Serum; Calcineurin Inhibitors; Graft Rejection; Graft Survival; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Intestines; Opportunistic Infections; Substance Withdrawal Syndrome; Tacrolimus; Transplantation Conditioning; Transplantation Tolerance; Transplantation, Homologous

Topics: Azathioprine; Cyclophosphamide; Cyclosporine; Diagnosis, Differential; Humans; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Methotrexate; Opportunistic Infections; Prednisolone; Prognosis; Tacrolimus

An immune function assay shows promise for identifying solid organ recipients at risk for infection or rejection. The following randomized prospective study was designed to assess the clinical benefits of adjusting immunosuppressive therapy in liver recipients based on immune function assay results.. Adult liver recipients were randomized to standard practice (control group; n = 102) or serial immune function testing (interventional group; n = 100) performed with a commercially available in vitro diagnostic assay (ImmuKnow; Viracor-IBT Laboratories, Lee's Summit, MO) before transplantation, immediately after surgery and at day 1, weeks 1 to 4, 6, and 8, and months 3 to 6, 9, and 12. The assay was repeated within 7 days of suspected/confirmed rejection/infection and within 1 week after event resolution.. Based on immune function values, tacrolimus doses were reduced 25% when values were less than 130 ng/mL adenosine triphosphate (low immune cell response) and increased 25% when values were greater than 450 ng/mL adenosine triphosphate (strong immune cell response). The 1-year patient survival was significantly higher in the interventional arm (95% vs 82%; P < 0.01) and the incidence of infections longer than 14 days after transplantation was significantly lower among patients in the interventional arm (42.0% vs. 54.9%, P < 0.05). The difference in infection rates was because of lower bacterial (32% vs 46%; P < 0.05) and fungal infection (2% vs 11%; P < 0.05). Among recipients without adverse events, the study group had lower tacrolimus dosages and blood levels.. Immune function testing provided additional data which helped optimize immunosuppression and improve patient outcomes.

Topics: Adenosine Triphosphate; Adult; Aged; Biomarkers; Drug Dosage Calculations; Drug Monitoring; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; Humans; Immunocompromised Host; Immunosuppressive Agents; Italy; Liver Transplantation; Male; Middle Aged; Monitoring, Immunologic; Opportunistic Infections; Predictive Value of Tests; Prospective Studies; Reagent Kits, Diagnostic; Steroids; Tacrolimus; Treatment Outcome

Mycophenolic acid (MPA) plasma concentrations are highly variable on standard-dose mycophenolate mofetil therapy. At creatinine clearances below 25 mL/min, MPA clearance increases as a result of a higher nonprotein-bound fraction. Patients with delayed graft function (DGF) after renal transplantation are exposed to low total MPA concentrations, when risk of rejection is highest. This study investigated the influence of DGF on MPA exposure and on clinical outcome.. Adult renal transplantation patients treated with mycophenolate mofetil, corticosteroids, and either microemulsified cyclosporine (n = 459) or tacrolimus (n = 371) participated in a randomized controlled trial (the Fixed-Dose Concentration-Controlled [FDCC] Study). Abbreviated MPA areas under the curve (AUCs) were obtained on Day 3, Day 10, Week 4, and Month 3, to calculate MPA AUC₀₋₁₂. Free MPA AUC values were available for a subgroup of patients (n = 269).. The overall incidence of DGF was 187 of 830 (23%) and did not differ between cyclosporine-treated (24%) and tacrolimus- (21%) treated patients. The incidence of biopsy-proven acute rejection at 12 months was significantly higher in patients with DGF (13.8% versus 21.4%). Patients with DGF had significantly lower dose-corrected MPA AUC on Day 3 and Day 10. Free MPA fraction and dose-corrected free MPA AUC were significantly higher in patients with DGF, from Day 3 until Month 3. The total number of patients with at least one opportunistic infection was significantly higher in patients with DGF (33.2%) compared with patients without DGF (25.8%) (P = 0.048). Patients with DGF developing opportunistic infections did not have higher total MPA AUC nor higher free MPA AUC compared with those without opportunistic infections.. Patients with DGF have significantly lower dose-corrected MPA AUC in the first month after renal transplantation, presumably as a result of enhanced MPA clearance on account of the elevated MPA free fraction. Because patients with DGF have a higher rate of acute rejection and lower MPA exposure, higher dosing of mycophenolate mofetil in such patients may improve outcome. However, the already increased incidence of opportunistic infections in patients with DGF is a concern.

Topics: Adrenal Cortex Hormones; Adult; Area Under Curve; Creatinine; Cyclosporine; Delayed Graft Function; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Opportunistic Infections; Tacrolimus; Treatment Failure

This open-label, randomized study compared the efficacy of a regimen of corticosteroids and tacrolimus (standard therapy group, n = 79) with a regimen of daclizumab induction therapy in combination with mycophenolate mofetil and tacrolimus (modified therapy group, n = 78) in primary liver transplant recipients. The primary endpoint was biopsy-proven acute rejection (BPAR) at 24 weeks. Secondary endpoints included time to rejection and patient and graft survival. The incidence of BPAR was significantly reduced in the modified therapy group compared to the standard therapy group (11.5% versus 26.6%, respectively, P = 0.017). The time to rejection was significantly shorter in the standard therapy group compared with the modified therapy group (P = 0.044). There was no significant difference between groups in patient or graft survival. Hepatitis C virus-positive patients exhibited no differences from hepatitis C virus-negative patients with respect to the incidence of BPAR. A steroid-sparing regimen of daclizumab, mycophenolate mofetil, and tacrolimus was effective and well tolerated in the prevention of BPAR in adult liver transplant recipients in comparison with a standard regimen of tacrolimus and steroids.

Topics: Acute Disease; Adolescent; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Daclizumab; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunoglobulin G; Immunosuppressive Agents; Incidence; Kaplan-Meier Estimate; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Prospective Studies; Steroids; Tacrolimus; Young Adult

To evaluate the efficacy and safety of a tacrolimus-based immunosuppressive regimen with and without induction therapy using daclizumab in first cadaveric renal transplant recipients.. Since January 2001, we studied the effect of daclizumab in a non-randomized and prospective study of 36 sequential first cadaveric renal transplant recipients. They were compared with a historical control group of 21 sequential first cadaveric renal transplant recipients without induction therapy. All patients received tacrolimus, azathioprine and corticosteroids as concomitant immunosuppressive therapy. Daclizumab was given at 1 mg/kg infusion 2 h before transplantation and then every 14 days for four more doses. Outcomes measured included incidence of acute rejection, patient survival, graft survival, annualized change in creatinine clearance (CrCl), cardiovascular risk profile, infection and malignancy.. Fewer biopsy proven acute rejections were observed in the induction treatment group: 11.1% (4/36) versus 19% (4/21) but the rejection free survival was similar (P = 0.37). The patient survival and graft survival were comparable. The renal function was similar in both groups. There were also no significant difference in infection, malignancy and cardiovascular risk profile in both groups.. Adding daclizumab to a tacrolimus-based therapy is safe but cannot further improve clinical efficacy.

Topics: Acute Disease; Adrenal Cortex Hormones; Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Azathioprine; Cardiovascular Diseases; Creatinine; Daclizumab; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney; Kidney Transplantation; Male; Middle Aged; Neoplasms; Opportunistic Infections; Prospective Studies; Tacrolimus; Time Factors; Treatment Outcome

Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens.. We randomly assigned 1645 renal-transplant recipients to receive standard-dose cyclosporine, mycophenolate mofetil, and corticosteroids, or daclizumab induction, mycophenolate mofetil, and corticosteroids in combination with low-dose cyclosporine, low-dose tacrolimus, or low-dose sirolimus. The primary end point was the estimated glomerular filtration rate (GFR), as calculated by the Cockcroft-Gault formula, 12 months after transplantation. Secondary end points included acute rejection and allograft survival.. The mean calculated GFR was higher in patients receiving low-dose tacrolimus (65.4 ml per minute) than in the other three groups (range, 56.7 to 59.4 ml per minute). The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus (12.3%) than in those receiving standard-dose cyclosporine (25.8%), low-dose cyclosporine (24.0%), or low-dose sirolimus (37.2%). Allograft survival differed significantly among the four groups (P=0.02) and was highest in the low-dose tacrolimus group (94.2%), followed by the low-dose cyclosporine group (93.1%), the standard-dose cyclosporine group (89.3%), and the low-dose sirolimus group (89.3%). Serious adverse events were more common in the low-dose sirolimus group than in the other groups (53.2% vs. a range of 43.4 to 44.3%), although a similar proportion of patients in each group had at least one adverse event during treatment (86.3 to 90.5%).. A regimen of daclizumab, mycophenolate mofetil, and corticosteroids in combination with low-dose tacrolimus may be advantageous for renal function, allograft survival, and acute rejection rates, as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with standard-dose cyclosporine without induction. (ClinicalTrials.gov number, NCT00231764 [ClinicalTrials.gov].).

Topics: Adrenal Cortex Hormones; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Calcineurin Inhibitors; Cyclosporine; Daclizumab; Diabetes Mellitus; Drug Therapy, Combination; Enzyme Inhibitors; Female; Glomerular Filtration Rate; Graft Rejection; Humans; Immunoglobulin G; Immunosuppressive Agents; Kaplan-Meier Estimate; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Prednisone; Sirolimus; Tacrolimus; Treatment Failure

Topics: Adrenal Cortex Hormones; Age Factors; Creatinine; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Humans; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Postoperative Complications; Prednisone; Tacrolimus; Time Factors; Transplantation, Homologous

The recent U.S. multicenter randomized trial of FK506 versus cyclosporine (CsA) demonstrated equivalent patient and graft survival in patients treated with FK506 and statistically fewer rejection episodes in the first year posttransplant.. To determine if more effective posttransplant immunosuppression was associated with an increased risk of cytomegalovirus (CMV) or posttransplant lymphoproliferative disease (PTLD), we examined the incidence of these two opportunistic infections during 3 years of follow-up.. CMV infection occurred in 40 (19.5%) FK506 and 40 (19.3%) CsA-treated patients. The incidence of CMV disease was 9.3% in FK506 and 6.8% in CsA-treated recipients; the most common site of CMV disease was the gastrointestinal tract. A multivariate analysis of several risk factors demonstrated that a CMV- recipient of a CMV+ donor was at greatest risk for CMV infection. The incidence of posttransplant lymphoproliferative disease was equal in the two treatment arms: six CsA- and five FK506-treated recipients.. The results of this study suggest that the superior efficacy of FK506 in the prevention of acute rejection was not associated with an increased risk of CMV or posttransplant lymphoproliferative disease compared with CsA.

Topics: Cyclosporine; Cytomegalovirus Infections; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Lymphoproliferative Disorders; Multivariate Analysis; Opportunistic Infections; Postoperative Complications; Tacrolimus

Mycophenolate mofetil (MMF) prolongs allograft survival in experimental animals, prevents acute rejection in humans, and has recently been approved for use in renal transplantation in combination with cyclosporine. Tacrolimus (Prograf) has been shown to be effective for the prevention and treatment of allograft rejection in liver transplantation. However, there has been limited experience with the combination of tacrolimus and MMF in liver transplantation.. This retrospective pilot study examined the results in 130 primary, consecutive, adult liver transplants under two separate immunosuppressive protocols. Patients in the study group received MMF (1 g p.o. b.i.d.), tacrolimus (0.1 mg/kg p.o. b.i.d.), and a standard steroid taper. MMF was also tapered and then discontinued within 3 months of transplantation. A historical control received tacrolimus (0.15 mg/kg p.o. b.i.d.) and the same steroid taper.. Pretransplant demographics, including creatinine, were not significantly different between the groups. The 6-month patient and graft survivals of 96.3% (control) versus 92.0% (study) were not significantly different. The incidence of acute rejection was 45.0% in the control group versus 26.0% in the study group (P = 0.03). The study group had a lower incidence of rejection (mean episodes/patient +/- SEM): 0.28+/-0.07 vs. 0.61+/-0.10 (P = 0.007). All of the study group members responded to high-dose steroids. In the control group, three patients required monoclonal antibody therapy and two patients required the addition of MMF. The incidence of cytomegalovirus was similar in the study group and the control group (13.8% vs. 10.0%, P = NS). Early renal function was better preserved in the tacrolimus/MMF group (mean creatinine +/- SEM): 1.09 mg/dl +/- 0.05 vs. 1.51 mg/dl +/- 0.08 at 30 days, P = 0.0001. The study design required dosing with less tacrolimus (mean mg/day +/- SEM), which was achieved at 1 week (23.2+/-0.7 vs. 13.5+/-0.5); 1 month (18.7+/-0.8 vs. 11.4+/-0.5); 3 months (14.5+/-0.6 vs. 9+/-0.5); and 6 months (11.6+/-0.6 vs. 8.2+/-0.6); P = 0.0001, for all time points.. Combination therapy with tacrolimus and MMF may significantly reduce the incidence of acute liver allograft rejection, allow a significant reduction in tacrolimus dosage, and decrease the incidence of nephrotoxicity. Long-term analysis will be necessary to assess any increased risk of opportunistic infections.

Topics: Drug Therapy, Combination; Female; Glucocorticoids; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Methylprednisolone; Middle Aged; Muromonab-CD3; Mycophenolic Acid; Opportunistic Infections; Pilot Projects; Retrospective Studies; Survival Analysis; Tacrolimus; Transplantation Immunology

We conducted a prospective, randomized, double-blind study comparing amphotericin B colloidal dispersion (ABCD) with amphotericin B in the empirical treatment of fever and neutropenia. Patients with neutropenia and unresolved fever after > or = 3 days of empirical antibiotic therapy were stratified by age and concomitant use of cyclosporine or tacrolimus. Patients were then randomized to receive therapy with ABCD (4 mg/[kg.d]) or amphotericin B (0.8 mg/[kg.d]) for < or = 14 days. A total of 213 patients were enrolled, of whom 196 were evaluable for efficacy. Fifty percent of ABCD-treated patients and 43.2% of amphotericin B-treated patients had a therapeutic response (P = .31). Renal dysfunction was less likely to develop and occurred later in ABCD recipients than in amphotericin B recipients (P < .001 for both parameters). Infusion-related hypoxia and chills were more common in ABCD recipients than in amphotericin B recipients (P = .013 and P = .018, respectively). ABCD appeared comparable in efficacy with amphotericin B, and renal dysfunction associated with ABCD was significantly less than that associated with amphotericin B. However, infusion-related events were more common with ABCD treatment than with amphotericin B treatment.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Colloids; Cyclosporine; Double-Blind Method; Female; Fever; Humans; Immunosuppressive Agents; Infant; Infusions, Intravenous; Kidney Function Tests; Male; Middle Aged; Mycoses; Neutropenia; Opportunistic Infections; Pilot Projects; Prospective Studies; Tacrolimus; Treatment Outcome

Topics: Adult; Aged; Biopsy; Cyclosporine; Endocardium; Female; Follow-Up Studies; Graft Rejection; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocarditis; Myocardium; Opportunistic Infections; Prospective Studies; Tacrolimus

We have reviewed our experience with conversion to tacrolimus after 435 liver transplantations. Tacrolimus was administered as a rescue agent in 33 patients until October 1993. Indications for rescue therapy were: cholestatic forms of severe, steroid-resistant cellular rejection (n = 8), OKT3-resistant cellular rejections (n = 6), cellular rejections in patients suffering from cyclosporin malabsorption (n = 4), late onset cellular rejections (n = 4), early chronic rejections (n = 3), and chronic vascular or ductopenic rejections (n = 8). Response was evident in 29 of the 33 patients (88%), whereas 4 patients (12%) were nonresponsive. Patient and graft survival were 76% and 70%, respectively. Graft loss with or without patient death occurred in three of eight patients suffering from severe, steroid-resistant cellular rejection, in two of six patients with OKT3-resistant cellular rejections, and in five of eight patients undergoing chronic rejection. In severe steroid-resistant cellular rejection, successful tacrolimus rescue therapy corresponded to a significantly lower total serum bilirubin than unsuccessful therapy (12.0 +/- 5.6 mg% vs 29.7 +/- 5.9 mg%, P < 0.05). We conclude that tacrolimus rescue therapy is a safe and efficient alternative for high-risk cases that do not respond to conservative treatment. In severe, steroid-resistant cellular rejection and in chronic ductopenic rejection, conversion to tacrolimus is beneficial only in a limited number of cases. A predictive parameter, which total serum bilirubin may prove to be in severe, steroid-resistant cellular rejection, is needed to select those cases that might benefit more from retransplantation than from conversion to tacrolimus.

Topics: Adult; Bilirubin; Creatinine; Cyclosporine; Female; Graft Rejection; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Muromonab-CD3; Opportunistic Infections; Reoperation; Steroids; Tacrolimus

FK506 has been proven effective for prevention and treatment of liver allograft rejection. Herein, we compare FK506-based immunosuppression with an effective quadruple immunosuppressive regimen, including cyclosporine and antithymocyte globulin. The results of a single center participating in the European multicenter FK506 study are reported, including immunosuppressive efficacy as well as toxicity. One-year patient and graft survival was 96.7% and 90.0% for the CsA group and 90.2% and 88.5% for the FK506 group, which is not statistically different. The incidence and severity of acute rejection episodes during the first postoperative year was similar in both treatment groups with 34.4% and 33.3% for the FK506 and CsA treatment group, respectively. Immunosuppressive potency was better for the FK506 group compared with the CsA group according to the incidence of chronic rejection. Furthermore, 5 patients (8.3%) required conversion to FK506 for immunological reasons, i.e., refractory acute or chronic rejection. The incidence of moderate and severe neurotoxicity during the early postoperative period was higher in the FK506 group (21.3%) compared with the CsA group (11.7%), while the incidence of renal insufficiency and acute renal failure was similar (18.0% and 18.3% for the FK506 and CsA treatment groups, respectively). The incidence of CMV infection was significantly higher under treatment with CsA (25.0%) than with FK506 (6.6%) (P < or = 0.05), while the incidence of pneumonia (13.1% and 13.3%), cholangitis (29.5% and 26.7%), and urinary tract infection (39.3% and 28.3% for the FK506 and CsA treatment groups, respectively) was similar in both treatment groups. However, infection was more serious in some cases treated with FK506, and evolved as the main cause of death in the FK506 treatment group. Therefore, caution should be paid to over immunosuppression and toxicity in FK506-treated patients. Regarding the monitoring of FK506, FK506 plasma level failed to be a reliable indicator, and therefore we recommend measurement of whole blood FK506 levels. Our data indicate that immunosuppressive potency of FK506 is greater than that of CsA, especially concerning the incidence of chronic rejection.

Topics: Adolescent; Adult; Aged; Cyclosporine; Cytomegalovirus Infections; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Nervous System Diseases; Opportunistic Infections; Renal Insufficiency; Survival Analysis; Tacrolimus; Transplantation, Homologous

Topics: Adult; Anti-Bacterial Agents; Diabetes Mellitus, Type 1; Female; Graft Rejection; Heart; Heart Transplantation; Humans; Hypertension; Immunosuppression Therapy; Immunosuppressive Agents; Infant; Kidney; Male; Middle Aged; Opportunistic Infections; Prospective Studies; Survival Analysis; Tacrolimus

Renal transplant patients are immunosuppressed and are at increased risk of opportunistic infections, including

Topics: Aged; Aged, 80 and over; Antilymphocyte Serum; Basiliximab; Brain Abscess; Cohort Studies; Cyclosporine; Female; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Male; Middle Aged; Nocardia; Nocardia Infections; Opportunistic Infections; Retrospective Studies; Tacrolimus; Treatment Outcome; United States

The efficacy and safety of minimisation of immunosuppression including early steroid withdrawal in kidney transplant recipients treated with Basiliximab induction remains unclear.. This retrospective cohort study reports the outcomes from 298 consecutive renal transplants performed since 1st July 2010-June 2013 treated with Basiliximab induction and early steroid withdrawal in low immunological risk patients using a simple immunological risk stratification and 3-month protocol biopsy to optimise therapy. The cohort comprised 225 low-risk patients (first transplant or HLA antibody calculated reaction frequency (CRF ≤50% with no donor specific HLA antibodies) who underwent basiliximab induction, steroid withdrawal on day 7 and maintenance with tacrolimus and mycophenolate mofetil (MMF), and 73 high-risk patients who received tacrolimus, MMF and prednisolone for the first 3 months followed by long term maintenance immunosuppression with tacrolimus and prednisolone. High-risk patients not undergoing 3-month protocol biopsy were continued on triple immunosuppression.. Steroid withdrawal could be safely achieved in low immunological risk recipients with IL2 receptor antibody induction. The incidence of biopsy-proven acute rejection was 15.1% in the low-risk and 13.9% in the high-risk group (including sub-clinical rejection detected at protocol biopsy). One- year graft survival was 93.3% and patient survival 98.5% in the low-risk group, and 97.3 and 100% respectively in the high-risk group. Graft function was similar in each group at 1 year (mean eGFR 61.2 ± 23.4 mL/min low-risk and 64.6 ± 19.2 mL/min high-risk).. Immunosuppression regimen comprising basiliximab induction, tacrolimus, MMF and prednisolone with early steroid withdrawal in low risk patients and MMF withdrawal in high risk patients following a normal 3-month protocol biopsy is effective in limiting acute rejection episodes and produces excellent rates of patient survival, graft function and complications.

Topics: Adult; Aged; Azathioprine; Basiliximab; Drug Administration Schedule; Female; Glucocorticoids; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Postoperative Care; Postoperative Complications; Prednisolone; Receptors, Interleukin-2; Renal Insufficiency, Chronic; Retrospective Studies; Risk Assessment; Tacrolimus; Young Adult

The clinical course and outcomes of immunocompromised patients, such as transplant recipients, with COVID-19 remain unclear. It has been postulated that a substantial portion of the disease burden seems to be mediated by the host immune activation to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we present a simultaneous heart-kidney transplant (SHKT) recipient who was hospitalized for the management of respiratory failure from volume overload complicated by failure to thrive, multiple opportunistic infections, and open non-healing wounds in the setting of worsening renal dysfunction weeks prior to the first case of SARS-CoV-2 being detected in the state of Connecticut. After his third endotracheal intubation, routine nucleic acid testing (NAT) for SARS-CoV-2, in anticipation of a planned tracheostomy, was positive. His hemodynamics, respiratory status, and ventilator requirements remained stable without any worsening for 4 weeks until he had a negative NAT test. It is possible that the immunocompromised status of our patient may have prevented significant immune activation leading up to clinically significant cytokine storm that could have resulted in acute respiratory distress syndrome and multisystem organ failure.

Topics: Antibiotics, Antineoplastic; Bacteremia; BK Virus; Cardiomyopathy, Dilated; Cardiotoxicity; COVID-19; COVID-19 Nucleic Acid Testing; Doxorubicin; Graft Rejection; Gram-Positive Bacterial Infections; Heart Transplantation; Humans; Immunocompromised Host; Immunosuppressive Agents; Incidental Findings; Kidney Failure, Chronic; Kidney Transplantation; Male; Malnutrition; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Polyomavirus Infections; Postoperative Complications; Prednisone; Renal Dialysis; SARS-CoV-2; Staphylococcal Infections; Surgical Wound Infection; Tacrolimus; Tracheostomy; Tumor Virus Infections; Vancomycin-Resistant Enterococci; Viremia; Water-Electrolyte Imbalance

Little is known regarding optimal tacrolimus (TAC) trough levels after 1 year post-transplant in stable kidney transplant recipients (KTRs) who have not experienced renal or cardiovascular outcomes. This study aimed to investigate the effect of 1-year post-transplant TAC trough levels on long-term renal and cardiovascular outcomes and opportunistic infections in stable KTRs.. KTRs receiving TAC with mycophenolate-based immunosuppression who did not experience renal or cardiovascular outcomes within 1 year post-transplant were enrolled from a multicenter observational cohort study. Renal outcome was defined as a composite of biopsy-proven acute rejection, interstitial fibrosis and tubular atrophy, and death-censored graft loss. Cardiovascular outcome was defined as a composite of de novo cardiomegaly, left ventricular hypertrophy, and cardiovascular events. Opportunistic infections were defined as the occurrence of BK virus or cytomegalovirus infections.. A total of 603 eligible KTRs were divided into the low-level TAC (LL-TAC) and high-level TAC (HL-TAC) groups based on a median TAC level of 5.9 ng/mL (range 1.3-14.3) at 1 year post-transplant. The HL-TAC group had significantly higher TAC trough levels at 2, 3, 4, and 5 years compared with the levels of the LL-TAC group. During the mean follow-up of 63.7 ± 13.0 months, there were 121 renal outcomes and 224 cardiovascular outcomes. In multivariate Cox regression analysis, LL-TAC and HL-TAC were not independent risk factors for renal and cardiovascular outcomes, respectively. No significant differences in the development of opportunistic infections and de novo donor-specific anti-human leukocyte antigen antibodies and renal allograft function were observed between the two groups.. TAC trough levels after 1 year post-transplant remained at a similar level until the fifth year after kidney transplantation and were not directly associated with long-term outcomes in stable Korean KTRs who did not experience renal or cardiovascular outcomes. Therefore, in Asian KTRs with a stable clinical course, TAC trough levels higher than approximately 6 ng/mL might not be required after a year of kidney transplantation.

Topics: Adult; Cardiovascular Diseases; Cohort Studies; Cytomegalovirus Infections; Female; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Opportunistic Infections; Polyomavirus Infections; Renal Insufficiency; Republic of Korea; Tacrolimus

Drug-drug interactions between azoles and calcineurin inhibitors can cause issues for organ transplant specialists. Clinical practice guidelines for the treatment of solid-organ transplant recipients with invasive aspergillosis infection are lacking. Here, we present a patient who developed pulmonary aspergillosis after liver transplant. The patient had prolonged treatment with echinocandin that was not effective. A drug-drug interaction between azoles and tacrolimus caused issues for the clinical physician. We adjusted the doses, and the patient was successfully treated. A reduction in the tacrolimus dose, intensive monitoring of associated parameters, and elimination of risk exposures are important for a favorable outcome.

Topics: Antifungal Agents; Calcineurin Inhibitors; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Graft Rejection; Graft Survival; Humans; Immunocompromised Host; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Opportunistic Infections; Pulmonary Aspergillosis; Tacrolimus; Treatment Outcome; Voriconazole

While several alternatives to cyclophosphamide have been proposed for refractory eosinophilic granulomatosis with polyangiitis (EGPA), therapeutic options are limited in patients with chronic infections. We report a case of refractory EGPA complicated by invasive aspergillosis and chronic hepatitis B. Although multiple immunosuppressants, including cyclophosphamide, were not effective, tacrolimus was used successfully to control disease without exacerbating concomitant infections in the long term. Tacrolimus could be an alternative choice in the treatment of EGPA, especially when aggressive immunosuppression is unfeasible.

Topics: Antifungal Agents; Antiviral Agents; Churg-Strauss Syndrome; Drug Substitution; Hepatitis B, Chronic; Humans; Immunocompromised Host; Immunosuppressive Agents; Invasive Pulmonary Aspergillosis; Male; Middle Aged; Opportunistic Infections; Tacrolimus; Treatment Outcome

The purpose of this study was to compare the safety and efficacy of generic tacrolimus (Tacrobell [TCB]) and a reference tacrolimus (Prograf [PGF]) in liver transplant recipients.. We retrospectively analyzed 167 patients who used TCB or PGF between January 2009 and March 2016 for >1 year (TCB group, n=86; PGF group, n=81). To assess the efficacy and safety of TCB, we evaluated the relationship between drug dose and trough level, survival, rejection, infection, kidney function, and side effects.. There was no difference in the preoperative demographics between the two groups. Moreover, there was no difference in the drug dose and trough level between the groups at 1 week after surgery. Coefficient of variation (CV) values were obtained at the drug trough level for each patient and no differences in CV values were identified within 1 year (. The generic tacrolimus, TCB, is a comparable alternative to the original tacrolimus, PGF, as a main immunosuppressive drug for liver transplantation.

Topics: Drug Monitoring; Drugs, Generic; Female; Graft Rejection; Graft Survival; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Diseases; Liver Transplantation; Male; Middle Aged; Opportunistic Infections; Retrospective Studies; Risk Factors; Tacrolimus; Therapeutic Equivalency; Time Factors; Treatment Outcome

Nocardiosis is a life-threatening opportunistic infection. Solid organ transplant (SOT) recipients are at higher risk (incidence 0.04%-3.5%) of developing nocardiosis. Rate of nocardiosis in the Southwestern US may be high due to environmental factors.. We performed a retrospective review study on 54 SOT patients diagnosed with Nocardia between 1997 and 2016 at our center. To explore the association of various risk factors with both the development of disseminated disease and mortality, a series of Fisher's exact tests was used.. Incidence of nocardiosis in SOT patients was 2.65%. Fisher's exact tests revealed no association between development of disseminated disease and the following variables: transplant rejection (P = 1), elevated tacrolimus levels (P = .4), and CMV viremia (P = .06). Also, we did not find any association between mortality and the variables we evaluated: type of transplant, transplant rejection, renal failure, disseminated nocardia, and patient's age. Overall mortality and 1-year mortality were 17% and 11%.. Based on our findings, daily 1 DS TMP/SMX prophylaxis did not appear to provide reliable protection against nocardiosis. However, we could not state definitely that TMP/SMX prophylaxis was or wasn't protective because of lack control group. None of the Fisher's exact tests revealed associations between the tested risk factors and either disease dissemination or mortality. This could be due to a true lack of association between the variables in each pair. However, it is also likely that our relatively small sample size limited our power to detect underlying relationships that may be present. Compared with other studies, 1-year mortality was lower at our institution (11% vs 16%).

Topics: Adult; Aged; Anti-Bacterial Agents; Female; Graft Rejection; Humans; Immunocompromised Host; Immunosuppressive Agents; Incidence; Male; Middle Aged; Nocardia; Nocardia Infections; Opportunistic Infections; Organ Transplantation; Retrospective Studies; Risk Factors; Southwestern United States; Tacrolimus; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Immunosuppression is a known risk for post-transplant infections. Little data exist on the risk contributions of specific agents for various infections.. A triply robust propensity score-adjusted analysis was performed in a renal transplant cohort between February 2006 and January 2014. The study was performed to identify the incidence and the risk factors for developing a post-transplant infection. After initial bivariate analysis, a triply robust propensity score-adjusted multivariate logistic regression was performed.. The mean age of the 717 renal transplant recipients was 50.0 ± 13.3 years, with the majority being male (61.6%) and 349 (48.7%) experiencing at least 1 post-transplant infection. Neither race, graft type, nor insurance status was associated with an increased incidence or risk of infection. In a fully adjusted regression model, the immunosuppressants mycophenolic acid mofetil (OR 0.38, 95% CI 0.21-0.71; P < .001) and alemtuzumab (OR 0.40, 95% CI 0.19-0.85; P = .020) were protective.. Alemtuzumab and mycophenolic acid mofetil as immunosuppressant agents in a multiagent protocol appear to decrease the incidence of infection. Cytomegalovirus antigenemia was the greatest risk for infection and mycophenolic acid mofetil possessed the greatest protective effect on viral infections.

Topics: Adult; Alemtuzumab; Case-Control Studies; Community-Acquired Infections; Cross Infection; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Infections; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Propensity Score; Retrospective Studies; Risk Factors; Tacrolimus; Virus Diseases

The aim of the study was to assess the frequency of infections caused by Pneumocystis jiroveci, Chlamydophila pneumoniae, Legionella pneumophila, and Mycoplasma pneumoniae among lung transplant recipients in the context of immunosuppression.. The study group consisted of 94 patients (37 women and 57 men; mean age 42.03 years) transplanted between 2009 and 2016 at the Silesia Center for Heart Diseases (SCCS). Immunosuppressive treatment (induction and maintenance therapy) was assessed. The immunofluorescence methods were used to detect the P. jiroveci, L. pneumophila, C. pneumoniae, and M. pneumoniae antigens in samples obtained from the respiratory tract.. Thirty-two of 94 graft recipients developed atypical or opportunistic infection. The median time of its occurrence was 178 days after transplantation. P. jiroveci was responsible for 84.38% of first infections. Five patients developed infection with P. jiroveci and C. pneumoniae. None of the infections occurred during induction of immunosuppression. An opportunistic or atypical infection developed in 19.35% of the patients treated with a tacrolimus-based regimen, and in 43.33% of patients on a cyclosporine-based regimen.. Infection with P. jiroveci is a recognized problem after lung transplantation and should be monitored. The percentage of infected patients is higher in patients treated with a cyclosporine-based regimen in comparison to those treated with tacrolimus.

Topics: Adult; Chlamydophila Infections; Chlamydophila pneumoniae; Cyclosporine; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Legionella pneumophila; Legionnaires' Disease; Lung Transplantation; Male; Middle Aged; Mycoplasma pneumoniae; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Mycoplasma; Pneumonia, Pneumocystis; Postoperative Complications; Tacrolimus; Transplant Recipients

Transplant recipients are treated with immunosuppressive (IS) therapies, which impact host-microbial interactions. We examined the impact of IS drugs on gut microbiota and on the expression of ileal antimicrobial peptides.. Mice were treated for 14 days with prednisolone, mycophenolate mofetil, tacrolimus, a combination of these 3 drugs, everolimus, or water. Feces were collected before and after treatment initiation. Ileal samples were collected after sacrifice. Fecal and ileal microbiota were analyzed by pyrosequencing of 16S rRNA genes and enumeration of selected bacteria by culture, and C-type lectins were assessed in ileal tissues by reverse transcriptase-quantitative polymerase chain reaction.. Prednisolone disrupted fecal microbiota community structure, decreased Bacteroidetes, and increased Firmicutes in the feces. Prednisolone, tacrolimus, and mycophenolate mofetil modified fecal microbiota at the family level in each experimental replicate, but changes were not consistent between the replicates. In ileal samples, the genus Clostridium sensu stricto was dramatically reduced in the prednisolone and combined IS drug groups. These modifications corresponded to an altered ileal expression of C-type lectins Reg3γ and Reg3β, and of interleukin 22. Interestingly, the combined IS treatment enabled a commensal Escherichia coli to flourish, and dramatically increased colonization by uropathogenic E. coli strain 536.. IS treatment alters innate antimicrobial defenses and disrupts the gut microbiota, which leads to overgrowth of indigenous E. coli and facilitates colonization by opportunistic pathogens.

Topics: Animals; Antimicrobial Cationic Peptides; Drug Therapy, Combination; Escherichia coli Infections; Feces; Gastrointestinal Microbiome; Host-Pathogen Interactions; Ileum; Immunocompromised Host; Immunosuppressive Agents; Lectins, C-Type; Mice, Inbred C57BL; Models, Animal; Mycophenolic Acid; Opportunistic Infections; Prednisolone; Reverse Transcriptase Polymerase Chain Reaction; Ribotyping; Tacrolimus; Time Factors; Urinary Tract Infections; Uropathogenic Escherichia coli

Nontuberculous mycobacterial infections can often occur in individuals with adequate immune function. Such infections typically have cutaneous involvement and are caused by rapidly growing mycobacterium. Other nontuberculous mycobacteria species, like Mycobacterium haemophilum, almost always present as opportunistic infections occurring in severely immunocompromised hosts. Here, we present a complicated and protracted course of diagnosing M. haemophilum lower extremity cutaneous infection in a matched-unrelated donor stem cell transplant recipient.

Topics: Anti-Bacterial Agents; Biopsy; Cellulitis; Ciprofloxacin; Clarithromycin; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Immunosuppression Therapy; Immunosuppressive Agents; Leukemia, Myeloid, Acute; Lower Extremity; Middle Aged; Mycobacterium haemophilum; Mycobacterium Infections, Nontuberculous; Opportunistic Infections; Rifabutin; Tacrolimus; Unrelated Donors

Although rabbit anti-thymocyte globulin (rATG) is commonly used as induction therapy for kidney transplantation, dosing is not standardized. Recently available findings suggest that even subtle differences in the cumulative dose of rATG induction may have an impact on acute rejection rates for patients receiving steroid-minimization maintenance immunosuppression. This investigation evaluated the potential consequences of rounding and capping rATG doses in patients receiving steroid-containing maintenance immunosuppression when calculating the dose based on actual body weight.. Single-center retrospective cohort study.. A large academic medical center.. A total of 261 adult kidney transplant recipients between July 1, 2010, and December 31, 2012, who received rATG induction and were maintained on tacrolimus, mycophenolate, and prednisone.. Incidences of biopsy-confirmed acute rejection, opportunistic infections and hematologic effects within 12 months posttransplant were assessed for patients receiving a cumulative rATG dose of 5 mg/kg or higher (5.2 ± 0.2 mg/kg, n=138) compared with those who received a cumulative rATG dose lower than  5 mg/kg (4.5 ± 0.6 mg/kg, n=123). The groups had similar baseline characteristics, immunologic risk, and indications for rATG induction. The incidence of clinically relevant biopsy-confirmed acute rejection was low and similar between the groups (8.7% for rATG of 5 mg/kg or higher vs 8.9% for rATG lower than  5 mg/kg, p=0.944). Patient survival, all-cause graft survival, and graft function did not differ between the groups. Incidences of cytomegalovirus and BK virus infection as well as the extent and duration of lymphopenia were also similar between the groups.. In combination with triple maintenance immunosuppression consisting of tacrolimus, mycophenolate, and prednisone, modest differences in the cumulative rATG dose were not associated with increased risk of acute rejection. Measures to optimize rATG utilization present opportunities for cost-saving without sacrificing efficacy in this patient population.

Topics: Adult; Animals; Antilymphocyte Serum; Blood Cell Count; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Prednisone; Rabbits; Retrospective Studies; Tacrolimus

Polyomavirus nephropathy is commonly seen in the renal allograft setting but is uncommon in native kidneys. This paper describes polyomavirus nephropathy that developed in the native kidneys of a patient following immunosuppressive therapy for rheumatoid arthritis/Sjögren's syndrome associated lung disease. The patient presented with dyspnoea and a slow steady rise in serum creatinine. Owing to chronic immunosuppression, calcineurin-inhibitor toxicity was suspected. However, renal biopsy revealed polyomavirus nephropathy. The treatment of choice, lowered immunosuppression, was complicated by exacerbation of the patient's lung disease. This case highlights features of polyomavirus nephropathy in the native kidney, as well as the difficulty in its treatment when immunosuppressive treatment is necessary for medical comorbidities.

Topics: Arthritis, Rheumatoid; Humans; Immunosuppressive Agents; Kidney Diseases; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Polyomavirus; Polyomavirus Infections; Pulmonary Fibrosis; Tacrolimus

Candida krusei is an important agent of opportunistic infections that often displays resistance to several antifungals. We describe here the in vivo acquisition of resistance to voriconazole (VRC) by C. krusei isolates recovered from a leukemia patient during a long period of VRC therapy. In order to mimic the in vivo development of VRC resistance, a susceptible C. krusei isolate was exposed daily to 1 μg/ml of VRC in vitro. Interestingly, after 5 days of exposure to VRC, a MIC of 4 μg/ml was achieved; this value remained constant after 25 additional days of treatment with VRC and also after 30 consecutive days of incubation in VRC-free medium. Our objective was to determine the associated molecular resistance mechanisms, such as expression of efflux pump genes and ERG11 gene mutations, among the resistant strains. Synergistic effects between the efflux blocker tacrolimus (FK506) and VRC were found in all of the resistant strains. Moreover, ABC1 gene expression increased over time in both the in vivo- and in vitro-induced resistant strains, in contrast to the ABC2 and ERG11 genes, whose expression was invariably lower and constant. ERG11 gene sequencing showed two different types of mutations, i.e., heterozygosity at T1389T/C, corresponding to synonymous mutations, in C. krusei strains and a missense mutation at position T418C, resulting in a change from Tyr to His, among resistant C. krusei clinical isolates. This study highlights the relevance of ATP-dependent efflux pump (namely, Abc1p) activity in VRC resistance and describes new mutations in the ERG11 gene among resistant C. krusei clinical isolates.

Topics: Adult; Antifungal Agents; Antineoplastic Agents; ATP-Binding Cassette Transporters; Candida; Candidiasis; Drug Resistance, Fungal; Fluconazole; Fungal Proteins; Gene Expression; Humans; Male; Mutation; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sterol 14-Demethylase; Tacrolimus; Voriconazole

Tacrolimus (FK506) has a superior immunosuppressive effect compared with cyclosporine (CSA) without a significant increase in generalized infectious complications. Differences in specific infections such as Clostridium difficile (CDI) have not been reported. We investigated the relationship between calcineurin inhibitors and CDI, hypothesizing that choice of calcineurin inhibitor (CSA or FK506) after lung transplantation would have no effect on the incidence of CDI.. We performed a retrospective chart review of lung transplant recipients between June 1, 2000, and December 31, 2005, at a single institution. Positive CDI assays through December 11, 2011, were also recorded. We used Student's t- and chi-squared tests (α = 0.05) to compare CSA and FK506 groups. We calculated adjusted hazard ratios for CDI using Cox proportional hazard models.. We identified 217 lung transplant recipients: 106 patients in the CSA group and 111 patients in the FK506 group. A total of 31 patients (27.9%) in the FK506 group developed CDI postoperatively compared with 20 patients (18.9%) in the CSA group (P = 0.16). The adjusted hazard ratio for CDI in the FK506 group was not significantly higher (1.53; 95% confidence interval, 0.78-2.98). There was no significant difference in the intensive care unit or total length of stay, in-hospital incidence rate, time to first CDI episode, or recurrence rate between groups.. The CDI rates were not significantly higher in the FK506 group than the CSA group in our study. These data are consistent with previous studies on FK506 that show no increase in infectious complications over CSA, and demonstrate its continued safety in lung transplantation.

Topics: Adolescent; Adult; Aged; Calcineurin Inhibitors; Child; Clostridioides difficile; Cyclosporine; Enterocolitis, Pseudomembranous; Female; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; Lung Transplantation; Male; Middle Aged; Multivariate Analysis; Opportunistic Infections; Proportional Hazards Models; Retrospective Studies; Tacrolimus; Young Adult

Topics: Antiviral Agents; BK Virus; Child; Female; Graft Rejection; Heart Transplantation; Humans; Immunosuppressive Agents; Isoxazoles; Kidney; Kidney Diseases; Leflunomide; Opportunistic Infections; Tacrolimus; Treatment Outcome; Viral Load; Viremia

This retrospective single-center study evaluated long-term renal function after conversion from calcineurin inhibitors to sirolimus-based immunosuppression in kidney transplant recipients.. From 2001 to 2009, one hundred fifty kidney transplant recipients were converted from calcineurin inhibitors to sirolimus at least 3 months after transplant.. After a mean follow-up of 171 weeks, 56.7% of converted patients remained on sirolimus. The 5-year survival rate of the patients (including intent-to-treat) and grafts was 85.5% and 83.6%. Patients on sirolimus showed significant improvement in renal function with a creatinine clearance of 50.9 ± 20.7 and 52.9 ± 20.8 mL/minute at month 0 and month 24. Independent predictive factors associated with a stable estimated glomerular filtration rate at the last follow-up of sirolimus patients were (1) having a living donor, (2) absence of anti-HLA alloantibodies at month 0, and (3) cyclosporine versus tacrolimus used before conversion. Adverse effects were reported in 134 patients (89.3%). They included (1) hospitalization for infection (n=52), (2) de novo proteinuria (n=40), and (3) eight patients with biopsy-proven acute rejection. Sirolimus was stopped and replaced by calcineurin inhibitors in 37 patients after a mean of 16 months treatment. After stopping sirolimus, renal-allograft function remained stable at 2 years.. Conversion of calcineurin inhibitors to sirolimus in kidney transplant recipients was associated with improved renal function. The reintroduction of calcineurin inhibitors was safe in patients who were withdrawn from sirolimus owing to adverse effects.

Topics: Adult; Aged; Calcineurin Inhibitors; Cyclosporine; Enzyme Inhibitors; Female; Follow-Up Studies; Glomerular Filtration Rate; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Neoplasms; Opportunistic Infections; Postoperative Complications; Proteinuria; Retrospective Studies; Sirolimus; Tacrolimus

The purpose of this study was to evaluate the radiological and clinical findings of invasive pulmonary aspergillosis (IPA) after liver transplantation.. This study included 25 consecutive liver transplant recipients with histologically confirmed IPA after liver transplantation. Radiological examinations performed for diagnosis were available in all patients. Clinical findings and changes in clinical response and radiological findings after treatment were also evaluated.. 3 main radiological findings were identified: nodules, 64% (16/25); masses, 36% (9/25); and consolidations in a patchy pattern, 20% (5/25). A tree-in-bud pattern was found in 12% (3/25) of patients. In 8 (32%) of 25 patients, we found a combination of 2 or more of these signs: 5 (20%) patients presented with concurrent nodules accompanied by patchy consolidations and/or tree-in-bud, and 3 (12%) patients showed masses accompanied by large consolidations. A halo sign was observed in 20 (80%) of 25 patients. Hypodense sign and cavitary lesions were encountered in 17 (68%) of 25 patients. Follow-up radiological findings after treatment showed improvement in 18 patients, no change in 4 patients and progression in 3 patients. There were three aspergillosis-associated deaths during the follow-up period. The onset time of IPA was a median of 31 days after transplantation. The most common symptom at diagnosis was fever (n=15). None of the 25 patients had leukopaenia at the time of the diagnosis of IPA.. The most common radiological findings of IPA after liver transplantation are multiple nodules with or without halo sign, masses and consolidations, which usually appear about 1 month after transplantation.

Topics: Adult; Aged; Consensus; End Stage Liver Disease; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Invasive Pulmonary Aspergillosis; Liver Transplantation; Male; Middle Aged; Multidetector Computed Tomography; Multiple Pulmonary Nodules; Opportunistic Infections; Prognosis; Retrospective Studies; Tacrolimus

Salmonellosis caused by Salmonella enteritidis is an acute and in most cases zoonotic disease, but chronic human carriers are also known. Mostly, affected persons recover without treatment, but severe complications occur occasionally. For the first time we report a case of probably food-borne invasive Salmonella enteritidis infection with septic shock in a patient with Tacrolimus treatment, 13 years after renal transplantation, probably acquired by uncooked ground pork meat.

Topics: Aged; Animals; Colitis; Cooking; Food Microbiology; Foodborne Diseases; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Meat; Opportunistic Infections; Salmonella enteritidis; Salmonella Infections; Shock, Septic; Swine; Tacrolimus; Tomography, X-Ray Computed

Balancing immunosuppression to prevent rejection while minimizing infection or drug toxicity risk is a major challenge in heart transplantation. Therapeutic drug monitoring alone is inadequate to measure the immune response. An immune monitoring (IM) assay (ImmuKnow; Cylex, Columbia, MD) performed on peripheral blood measures adenosine triphosphatase (ATP) release from activated lymphocytes and may predict the immune state. Therefore, we sought to determine the utility of IM in heart transplant recipients.. Between November 2005 and July 2008, 296 heart transplant recipients had a total of 864 IM assays performed at 2 weeks to 10 years post-transplant and were correlated with infection and rejection events that occurred within 1 month after IM testing. All patients received standard triple-drug immunosuppressive therapy with tacrolimus, mycophenolate mofetil and corticosteroids, without induction therapy.. There were 38 infectious episodes and 8 rejection episodes. The average IM score was significantly lower during infection than steady state (187 vs 280 ng ATP/ml, p < 0.001). The average IM score was not significantly different during rejection when compared with steady state (327 vs 280 ng ATP/ml, p = 0.35). Interestingly, 3 of 8 rejection episodes were antibody-mediated rejections and had hemodynamic compromise and, for these, the mean IM score was significantly higher than for steady-state patients (491 vs 280 ng ATP/ml, p < 0.001).. The non-invasive IM test appears to predict infectious risk in heart transplant patients. The association between high IM scores and rejection risk is inconclusive due to the small number of rejection episodes. Further studies with larger sample sizes for rejection episodes are required.

Topics: Adenosine Triphosphate; Adult; Aged; Biopsy; CD4-Positive T-Lymphocytes; Drug Therapy, Combination; Endocardium; Follow-Up Studies; Graft Rejection; Heart Transplantation; Humans; Immunosuppressive Agents; Lymphocyte Activation; Male; Middle Aged; Monitoring, Immunologic; Mycophenolic Acid; Myocardium; Opportunistic Infections; Prednisolone; Proportional Hazards Models; Risk Assessment; Tacrolimus

Mycophenolate mofetil (MMF) is routinely used at a fixed dose, but several factors interact to alter the blood level of mycophenolic acid (MPA), resulting in toxicity or treatment failure.. From January 2007 to December 2008, 85 kidney transplantation patients were given a fixed dose of 1.5 g/d of MMF in 12-hour intervals. MPA trough levels were measured on postoperative 1 week, 1 month, 3 months, 6 months, and 12 months.. Mean age of patients was 41 years. Thirty five cases were deceased donor kidney transplantations and 50 were living donor kidney transplantations. Mean trough levels of MPA were 1.04 microg/mL, 1.09 microg/mL, 1.28 microg/mL, 1.83 microg/mL, and 1.69 microg/mL at postoperative 1 week, 1 month, 3 months, 6 months, and 12 months, respectively. Mean trough levels of the subgroup of patients taking cyclosporine were 0.82 microg/mL, 0.94 microg/mL, 1.01 microg/mL, 1.56 microg/mL, and 1.46 microg/mL (n=36). Mean trough levels of the subgroup of patients taking tacrolimus were 1.19 microg/mL, 1.21 microg/mL, 1.56 microg/mL, 2.13 microg/mL, and 2.20 microg/mL (n=49). At 12 months, 31% of all patients experienced one or more opportunistic infections. Eight patients (9.4%) had cytomegalovirus infections, 14 patients (16.5%) had polyomavirus infections, and four patients (4.7%) had parvovirus infections. Ten patients (11.8%) experienced biopsy-proven acute rejection during the follow-up period.. Mean MPA trough levels of patients on 1.5 g/d of MMF reached 1.0 microg/mL within 1 week. Thirty one percent of patients experienced opportunistic infections, and 11.8% of patients had biopsy-proven acute rejections.

Topics: Adult; Cadaver; Cyclosporine; Female; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Mycophenolic Acid; Opportunistic Infections; Postoperative Complications; Retrospective Studies; Tacrolimus; Time Factors; Tissue Donors

Here we report 2 cases of fatal Pneumocystis jirovecii pneumonia in patients with severe ulcerative colitis receiving combination immunosuppression including tacrolimus. We discuss the necessity of a P. jirovecii prophylaxis especially in elderly patients according to the European evidence-based consensus on the prevention and management of opportunistic infections in inflammatory bowel disease.

Topics: Aged; Colitis, Ulcerative; Fatal Outcome; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Male; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Risk Factors; Tacrolimus

Topics: Adult; Antiviral Agents; Critical Care; Diagnosis, Differential; Disease Outbreaks; Drug Resistance, Viral; Drug Therapy, Combination; Female; Hepatitis C, Chronic; Humans; Immunosuppressive Agents; Influenza A Virus, H1N1 Subtype; Influenza, Human; Intensive Care Units; Kidney Failure, Chronic; Liver Cirrhosis; Liver Transplantation; Opportunistic Infections; Oseltamivir; Postoperative Complications; Prednisone; Respiratory Insufficiency; Tacrolimus

Topics: Adrenal Cortex Hormones; Bacterial Infections; Calcineurin Inhibitors; Child; Cyclosporine; Humans; Immunosuppressive Agents; Opportunistic Infections; Tacrolimus

: 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

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Dermatitis, Atopic; Dermatologic Agents; Female; Herpes Simplex; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Middle Aged; Opportunistic Infections; Retrospective Studies; Tacrolimus

Deep dermatophytosis and nocardiosis are uncommon infections. This article describes a patient who was immunosuppressed with deep dermatophytosis caused by Trichophyton rubrum and concurrent disseminated nocardiosis. The infections occurred 16 years after the patient underwent renal transplantation, and may have been related to tacrolimus therapy.

Topics: Dermatomycoses; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Nocardia asteroides; Nocardia Infections; Opportunistic Infections; Tacrolimus; Trichophyton

To report a case of cytomegalovirus (CMV) retinitis in a patient immunosuppressed with FK 506.. Interventional case report.. Retrospective institutional study. One patient, diagnosed with bilateral CMV retinitis while on immunosuppressive treatment with FK 506, received systemic ganciclovir and intravitreal, slow-release ganciclovir implant in one eye, combined with reduction in FK 506 dose. Main outcome measures were visual acuity and regression of CMV retinitis.. Visual acuity at presentation was 20/20 in the right eye and 20/50 in the left eye. During the 6 months of follow-up, there was no change in visual acuity in either eye. The areas of CMV retinitis demonstrated progressive regression, leaving diffuse retinal atrophy.. Cytomegalovirus retinitis can be a sight-threatening complication of immunosuppressive treatment with FK 506. Ganciclovir treatment together with a reduction in FK 506 dose was effective in preserving vision.

Topics: Adult; Antiviral Agents; Cytomegalovirus Retinitis; Drug Implants; Female; Ganciclovir; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Opportunistic Infections; Retrospective Studies; Tacrolimus; Visual Acuity

The purpose of this study was to evaluate the risk of cutaneous infection in patients with atopic dermatitis treated with tacrolimus ointment.. Data for 1554 patients with atopic dermatitis, treated with tacrolimus ointment in 5 clinical trials, were analyzed.. In 3 controlled studies, the 12-week adjusted incidence of all cutaneous infections in patients treated with the vehicle, 0.03%, and 0.1% tacrolimus ointment, respectively, was 18.0%, 24.8%, and 17.7% for adult patients, and 20.9%, 19.6%, and 23.6% for pediatric patients. The incidence of any individual cutaneous infection was not significantly higher in the tacrolimus group than in the vehicle group, with the exception of folliculitis in adults. In two open-label studies, there was no evidence of an increased risk of cutaneous infections with long-term use of 0.1% tacrolimus ointment (up to 1 year), based on the incidence of adverse events, incidence by cumulative length of exposure, or hazard rates.. Treatment with tacrolimus ointment (0.03% or 0.1%) does not increase the risk of cutaneous bacterial, viral, or fungal infections in patients with atopic dermatitis.

Topics: Adolescent; Adult; Child; Child, Preschool; Clinical Trials as Topic; Dermatitis, Atopic; Double-Blind Method; Female; Folliculitis; Humans; Immunosuppressive Agents; Male; Opportunistic Infections; Skin Diseases, Infectious; Tacrolimus

Infection due to cytomegalovirus (CMV) is the most frequent opportunistic infection following renal transplantation (RT). It is usually asymptomatic. Cytomegalovirus disease causes fever leucopenia, thrombocytopenia and slightly elevated transaminases. The development of severe invasive forms is uncommon nowadays with post-transplantation monitoring, prophylactic regimens in high-risk patients and early treatment with ganciclovir. We report two renal transplant recipients who presented with severe gastrointestinal bleeding as the first manifestation of CMV disease at 9 and 14 weeks after transplantation. In both patients repeated post-transplantation pp65 antigenemia monitoring was negative. One patient developed hypovolemic shock due to severe rectal bleeding; an atypical bleeding ulcer was detected in the ileocecal valve. The other patient presented with upper gastrointestinal hemorrhage from a bleeding duodenal ulcer. Histological and immunohistochemical study confirmed the diagnosis. Both patients were elderly and on triple therapy with tacrolimus, mycophenolate and prednisone. We discuss the role of mycophenolate and the new immunosuppressant agents as factors favoring a state of enhanced immunosuppression, which may facilitate the onset of severe atypical forms of CMV disease.

Topics: Aged; Cytomegalovirus; Cytomegalovirus Infections; Disease Susceptibility; Duodenal Ulcer; Gastrointestinal Hemorrhage; Humans; Ileal Diseases; Ileocecal Valve; Immunocompromised Host; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Postoperative Complications; Prednisone; Shock; Tacrolimus; Ulcer

Topics: BK Virus; Humans; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Mycophenolic Acid; Opportunistic Infections; Polyomavirus Infections; Tacrolimus

Scopulariopsis brevicaulis is a causal agent of onchomycosis. We report the unusual clinical manifestations caused by this opportunist fungus.. A 61-year-old man consulted in February 1997 for a budding lesion located on the right medial malleolus. This patient had had a liver transplantation for primary biliary cirrhosis in 1990 and had been taking prednisone and cyclosporine since this time. Cyclosporine had been recently replaced by tacrolimus. The histology examination of a lesion specimen taken from the ankle evidenced a dermal mycosis due to opportunist filamentous fungus. Total excision was performed. The patient then developed nodular lesions of the left elbow during the summer of 1997. Mycology culture of a skin biopsy grew numerous colonies of Scopulariopsis brevicaulis. Excision of the elbow lesion was delayed due to hospitalization for suspected graft rejection and development of insulin-dependent diabetes. The elbow lesion was then resected followed by a skin graft. The mycology examination identified the same causal agent.. This liver transplant recipient developed two unusual extra-ungual localizations (ankle and elbow) of a Scopulariopsis brevicaulis infection. Chronic immunosuppression favored development of the infection with a pseudo-epithéliomatous presentation. The histology and mycology examinations were necessary for positive diagnosis.

Topics: Biopsy; Cyclosporine; Dermatomycoses; Humans; Immunocompromised Host; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Mitosporic Fungi; Opportunistic Infections; Prednisone; Tacrolimus

Topics: Animals; Antifungal Agents; Azoles; Candida albicans; Candidiasis; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Immunocompromised Host; Immunosuppressive Agents; Opportunistic Infections; Tacrolimus

In a retrospective analysis we compared the outcome of a group of 63 kidney or kidney/pancreas transplant recipients who were transplanted between June 1994 and February 1997 and received either tacrolimus (FK, n = 22) or Neoral (NEO, n = 41) as part of a triple immunosuppressive protocol. Ten patients in the NEO group has recurrent rejection episodes between 1 and 8 months post-transplant and were converted to FK. CellCept was the secondary immunosuppressive agent in about half the FK, three-quarters of the NEO, and in all but one in the conversion (CON) groups. Patients in all groups were on prednisone in equal amounts. Mean duration of follow-up for FK, NEO and CON groups was 32, 19 and 13 months, respectively. One-yr patient and graft survival was 100% in all groups. At 2 yr, graft survival was 95, 96 and 100% in FK, NEO and CON groups, respectively. Acute rejection at 1 yr was twice as high in the NEO group as the FK group. There were no rejection episodes among the FK patients who also received CellCept. The mean current serum creatinines (mg%) were: FK = 1.6, NEO = 1.8, CON = 1.9. Recurrent infection was more common with FK (8/22) than NEO (1/31) (p = 0.023). Our experience suggests there is less rejection but more infection in recipients treated with FK compared to NEO. In patients with recurrent rejection, conversion from NEO to FK stabilizes renal function and minimizes subsequent rejection episodes.

Topics: Creatinine; Cyclosporine; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Opportunistic Infections; Pancreas Transplantation; Recurrence; Retrospective Studies; Tacrolimus

Infection with Nocardia spp. is an uncommon but important cause of morbidity and mortality in organ transplant recipients. Cotrimoxazole prophylaxis against urinary tract infection and Pneumocystis carinii pneumonia in these patients usually prevents nocardial infection also. We report the case of a patient on tacrolimus and mycophenolate mofetil who developed drug-induced diabetes mellitus followed by nocardial brain infection. This infection occurred despite conventional cotrimoxazole prophylaxis. Physicians should be aware that newer, more potent and more diabetogenic immunosuppressive regimens may increase the risk of opportunistic infections such as nocardiosis, even in the presence of "adequate" antimicrobial preventive measures.

Topics: Adult; Anti-Bacterial Agents; Brain Abscess; Diabetes Mellitus; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Nocardia asteroides; Nocardia Infections; Opportunistic Infections; Tacrolimus; Trimethoprim, Sulfamethoxazole Drug Combination

Opportunistic infections are common after renal transplantation because of the use of immunosuppression. Nocardiosis is a rare but important cause of morbidity and mortality among renal transplant recipients. Depending upon the transplant center, the estimated incidence of nocardiosis among renal transplant recipients varies widely from 0 to 20%. We report the first case of nocardiosis in a recently transplanted renal patient maintained on tacrolimus, prednisone, and mycophenolate mofetil. It is likely that the nocardial infection in our patient was related to the development of her diabetes mellitus, and to her early episode of rejection and treatment which included high-dose steroids, and the addition of mycophenolate mofetil. Our case illustrates the importance of maintaining a heightened awareness so that nocardiosis may be diagnosed early and treated successfully.

Topics: Diabetes Complications; Female; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; IMP Dehydrogenase; Incidence; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Nocardia asteroides; Nocardia Infections; Opportunistic Infections; Prednisone; Risk Factors; Tacrolimus

Invasive cryptococcal infections have been reported in 0.3-1% of the patients undergoing liver transplantation in the previous reports. In contrast, invasive cryptococcosis developed in 6% of 102 consecutive liver transplants at our institution receiving tacrolimus as primary immunosuppression. Cutaneous and/or osteoarticular infections due to cryptococcus were detected in 67% of the patients with cryptococcosis, whereas meningitis was present only in 17%. One of the six patients with cryptococcosis presented with refractory shock and multiorgan system failure attributable solely to cryptococcosis. Patients with cryptococcal infections were significantly older than all other liver transplant recipients (p = 0.017), suggesting reactivation as opposed to primary infection as pathogenesis of cryptococcosis. 100% of the patients with cryptococcosis resided on the Eastern coast of the United States as compared to 59% of the patients without cryptococcosis (p = 0.08). There was no difference in the severity of underlying liver disease, degree of immunosuppression or CMV infection or disease between patients who did and did not develop cryptococcosis. Atypical manifestations, e.g. cutaneous diseases or sepsis syndrome, as opposed to subclinical meningitis, may be a clinical feature of cryptococcal infection in liver transplant recipients.

Topics: Adult; Aged; Antibiotic Prophylaxis; Cryptococcosis; Female; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Opportunistic Infections; Prospective Studies; Risk Factors; Survival Rate; Tacrolimus; United States

Acute myocardial rejection refractory to treatment still contributes significantly to patient death after intrathoracic transplantation. A historical series of 25 patients who received OKT3 (5 mg/day for 10 days) was compared with our current experience with 14 patients treated with tacrolimus (0.1 mg/kg/day targeting whole blood concentrations of 13 to 18 ng/ml): all 39 patients having persistent rejection unresponsive to treatment at the time of conversion. Mean periods of follow-up were 842.9 days and 342.6 days, respectively. Actuarial 1-year patient survival rates were 64.0% and 76.2% for the OKT3 and tacrolimus treatment groups, with most of the deaths in the OKT3 group occurring early (p = 0.064). Causes of death for patients receiving OKT3 included acute rejection (n = 5), infection (n = 3), carcinoma (n = 2), multiorgan failure (n = 1) and graft vessel disease (n = 1). The two deaths in the tacrolimus treatment group were the result of infections. Eighty percent of patients treated with OKT3 subsequently experienced further rejection episodes, in many cases necessitating methotrexate therapy. In contrast, only one patient (7.1%) from the tacrolimus group was diagnosed with rejection after conversion (p < 0.001). In conclusion, when compared with OKT3 therapy, a switch in baseline immunosuppression from cyclosporine to tacrolimus seems to be markedly more effective, as well as being safe for the treatment of persistent acute rejection.

Topics: Actuarial Analysis; Acute Disease; Adult; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Graft Rejection; Heart Transplantation; Heart-Lung Transplantation; Humans; Immunosuppressive Agents; Lung Transplantation; Male; Middle Aged; Muromonab-CD3; Opportunistic Infections; Survival Analysis; Tacrolimus; Treatment Outcome

The incidence of Epstein-Barr virus (EBV) infection and lymphoproliferative disorder (LPD) was determined in a pediatric liver transplant population consisting of 51 children treated with FK506 and 91 treated with cyclosporine. The incidence of symptomatic EBV infection was 21.9% (23 of 105 cases) in children < 5 yr old and 10.8% (4 of 37 cases) in children 5 to 17 yr old as compared with 2.7% (9 of 323 cases) in adults (P < 0.0001). In the under 5 yr old group on cyclosporine, the incidences of EBV infection and LPD were 9 of 68 (13.2%) and 2 of 68 children, (2.9%), respectively. In contrast, in children under 5 yr old group on FK506, the incidences of EBV infection and LPD in the FK506 group were 14 of 37 (37.8%) and 7 of 37 children (18.9%), respectively. The difference between these two groups was statistically significant (P < 0.02). There were no cases of LPD in the 5-17 yr-old children on either cyclosporine (n = 23) or FK506 (n = 14). The incidence of EBV infections in the 5 to 17 yr age group, 17.4% on cyclosporine and 0% on FK506, was less than for the younger children on FK506 (37.8%). A total of 39% (9 of 23) of children under 5 yr old who had symptomatic EBV infections developed LPD, and 44% (4 of 9) with LPD died. The higher incidence of EBV infections and LPD in the younger children treated with FK506 was probably related to a greater intensity of immunosuppression for patients on FK506 than those on cyclosporine.

Topics: Adolescent; Age Factors; Child; Child, Preschool; Cyclosporine; Graft Rejection; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Liver Transplantation; Lymphoproliferative Disorders; Opportunistic Infections; Retrospective Studies; Tacrolimus; Tumor Virus Infections

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Humans; Immunosuppressive Agents; Liver Transplantation; Mycoses; Opportunistic Infections; Risk Factors; Tacrolimus; Virus Diseases