sirolimus and Opportunistic-Infections

Topics: Abatacept; Calcineurin Inhibitors; Carcinoma, Squamous Cell; Desensitization, Immunologic; Graft Rejection; Hand Disinfection; Heart Failure; HLA Antigens; Humans; Immunoconjugates; Immunomodulation; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Mesenchymal Stem Cell Transplantation; Opportunistic Infections; Peritoneal Dialysis; Plasmapheresis; Postoperative Complications; Prognosis; Renal Dialysis; Renal Insufficiency; Sirolimus; Skin Neoplasms

The use of sirolimus (SRL) in orthotopic liver transplantation (OLT) has been controversial after experimental data suggested an increased risk of hepatic artery thrombosis (HAT). To assess the safety and efficacy of SRL as de novo immunosuppression in OLT recipients. Outcomes of 252 OLT patients who received SRL were compared with outcomes of 291 OLT recipients who received calcineurin inhibitor in a retrospective study. Primary outcomes of this study were: patient- and graft survivals, vascular, biliary, wound complications and rejection rates. Secondary outcomes were: postoperative infection rate, bone marrow and renal function and changes of lipid levels. Patient- and graft survivals, rejection and infection rates were similar. In the SRL group, HAT occurred in 1.2%, biliary complications in 19.4%, and incisional hernias in 9.1%. In the control group the incidence of HAT was 5.8% (P = 0.004), biliary complications 18.5% (P = NS) and incisional hernias 7.2% (P = NS). Patients on SRL experienced significantly higher levels of serum triglycerides but fewer acute cellular rejections. Bone marrow and renal functions were similar in both the groups. Our findings would suggest that SRL is safe and effective for very selected OLT recipients. Randomized controlled trials are necessary to confirm our results.

Topics: Adult; Bile Duct Diseases; Bone Marrow; Calcineurin Inhibitors; Cohort Studies; Female; Graft Rejection; Graft Survival; Hepatic Artery; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Kidney; Lipids; Liver Transplantation; Male; Middle Aged; Opportunistic Infections; Postoperative Complications; Retrospective Studies; Sirolimus; Surgical Wound Infection; Thrombosis; 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: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Cadaver; Cyclosporine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Graft Survival; Humans; Hypercholesterolemia; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Middle Aged; Opportunistic Infections; Placebos; Postoperative Complications; Risk Factors; Sirolimus; Survival Rate; Thrombocytopenia; Time Factors; Tissue Donors; Transplantation, Homologous; Triglycerides

Everolimus has important clinical activity in various malignancies, but its use can be complicated by respiratory adverse events. Important everolimus-induced respiratory adverse events are interstitial lung disease (ILD) and infections, either typical or opportunistic. Furthermore, non-everolimus-related respiratory events can occur. Due to the non-specific presentation of most of these respiratory disorders, it is often not possible to differentiate between these causes on clinical and radiological grounds only. Considering the potential fatal nature of opportunistic infections, these are especially important to recognize. To be able to distinguish between ILD and (opportunistic) infections as the underlying cause, an aggressive diagnostic workup, including bronchoalveolar lavage, should be performed in patients treated with everolimus who develop respiratory disease. We report three cases of severe opportunistic pulmonary infections during everolimus treatment, concerning two Pneumocystis jirovecii pneumonia infections. These cases illustrate the diagnostic challenges of respiratory adverse events and the importance of a thorough diagnostic workup for correct diagnosis and treatment.

Topics: Antineoplastic Agents; Everolimus; Female; Humans; Male; Middle Aged; Opportunistic Infections; Respiratory Tract Infections; Sirolimus

Everolimus, an mTOR inhibitor with immunosuppressive properties, is used in several types of advanced tumors. Materials and. We describe the first two cases of Pneumocystis jirovecii pneumonia in patients given everolimus for metastatic pancreatic neuroendocrine tumors.. The first patient presented with respiratory symptoms in the context of grade 4 lymphopenia 2 weeks after starting everolimus; the diagnosis of Pneumocystis jirovecii pneumonia was made post-mortem. After suspecting everolimus-related interstitial pneumonitis in the second patient, Pneumocystis jirovecii was detected, and cotrimoxazole therapy led to a favorable outcome.. Everolimus may induce pneumonitis, lymphopenia and opportunistic infections. The time from treatment initiation to opportunistic infection may be short. Risk factors in oncology deserve further identification in order to start prophylaxis without delay.

Topics: Antineoplastic Agents; Everolimus; Humans; Immunosuppressive Agents; Male; Middle Aged; Neuroendocrine Tumors; Opportunistic Infections; Pancreatic Neoplasms; Pneumocystis carinii; Pneumonia; Protein Kinase Inhibitors; Sirolimus; TOR Serine-Threonine Kinases

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

Cytomegalovirus (CMV) infection remains a major problem in recipients with heart transplantation (HTx), because it may play a significant role in the development of cardiac allograft vasculopathy, which is one of the major causes of death after HTx. Valganciclovir (VGC) is effective for the treatment of CMV infection, but is often associated with neutropenia, especially when used with mycophenolate mophetil (MMF). We experienced an HTx recipient with positive CMV antigenemia who suffered progressive neutropenia after administration of VGC. We switched MMF to everolimus (EVL) and assay for CMV antigenemia was constantly negative even after discontinuation of VGC. In all other 14 HTx recipients who received EVL for any reason, we found that assay for CMV antigenemia remained negative throughout the period of EVL administration. Considering the prophylactic effect on CMV, EVL can not only be an alternative to rescue from comorbidity, but might also be indicated earlier especially in CMV-seronegative HTx recipients.

Topics: Adult; Antigens, Viral; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Substitution; Drug Therapy, Combination; Everolimus; Ganciclovir; Heart Transplantation; Heart-Assist Devices; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Neutropenia; Opportunistic Infections; Sirolimus; Valganciclovir

Topics: Amino Acid Transport System y+L; Antibiotic Prophylaxis; Astrocytoma; Brain Neoplasms; Everolimus; Humans; Leukocyte Count; Opportunistic Infections; Sirolimus; TOR Serine-Threonine Kinases; Tuberous Sclerosis

Malignancies and opportunistic infections are frequently observed after solid-organ transplantation. Their occurrence strongly affects recipient survival. We report the case of a 29-year-old Tunisian kidney-recipient who was diagnosed simultaneously with post-transplant lymphoproliferative disease (PTLD) and visceral leishmaniasis (VL). Withdrawal of immunosuppressive therapy together with antiparasitic treatment using liposomal amphotericin B, and anti-CD20 antibodies medication resulted in cure of leishmaniasis and remission from PTLD. This case is of clinical interest because of the uncommon association of VL with PTLD after solid organ transplantation. It is also original by the favourable outcome of VL and PTLD, both known as life-threatening diseases. Also, it illustrates the predisposing role of immunosuppressive therapy in occurrence of opportunistic infections and malignancies after solid organ transplantation.

Topics: Adult; Amphotericin B; Antibodies, Monoclonal, Murine-Derived; Antiprotozoal Agents; Antiviral Agents; Epstein-Barr Virus Infections; Ganciclovir; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Leishmaniasis, Visceral; Lymphoproliferative Disorders; Male; Meglumine; Meglumine Antimoniate; Opportunistic Infections; Organometallic Compounds; Postoperative Complications; Remission Induction; Rituximab; Sirolimus

Topics: Graft Rejection; Hemofiltration; Humans; Kidney Diseases; Kidney Neoplasms; Kidney Transplantation; Opportunistic Infections; Renal Dialysis; Sirolimus; Tissue Donors; Tissue Engineering; Urinary Tract Infections

Several of the new immunosuppressive agents that are used to treat transplant recipients possess in vitro activity against specific pathogens, enhance the activity of antimicrobial agents, or have unique drug interactions with antimicrobial agents. Mycophenolate mofetil may have a protective effect against Pneumocystis carinii; it also enhances the activity of ganciclovir and has strong antiviral activity against human immunodeficiency virus type 1. High doses of mycophenolate mofetil have been associated with a higher frequency of tissue-invasive cytomegalovirus disease but not with asymptomatic cytomegalovirus infection. Rapamycin exhibits potent in vitro fungicidal activity against Cryptococcus neoformans and several pathogenic fungi in transplant recipients; however, it is not known whether its immunosuppressive effect in organ transplant recipients outweighs its antifungal activity. Recognition of the unique characteristics of these agents and the evolving spectrum of opportunistic infections has implications for the differential diagnosis, management, and prophylaxis of infections in organ transplant recipients in the modern immunosuppressive era.

Topics: Anti-Infective Agents; Antibodies, Monoclonal; Bacterial Infections; Clinical Trials as Topic; Drug Interactions; Humans; Immunosuppressive Agents; Opportunistic Infections; Organ Transplantation; Sirolimus