tacrolimus and Pneumonia--Pneumocystis

There is still no consensus on the optimal management of COVID-19 within the general population due to the emerging evidence base. High-risk groups, including kidney transplant recipients living with HIV present unique additional challenges. Here we discuss two kidney transplant recipients living with HIV with SARS-CoV-2 infection and their clinical course, and review the existing literature for this subset of challenging patients.

Topics: Adult; Anti-Bacterial Agents; Anti-HIV Agents; Atovaquone; CD4 Lymphocyte Count; CD4-CD8 Ratio; COVID-19; Dideoxynucleosides; Female; Glucocorticoids; Graft Rejection; HIV Infections; HIV-1; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Lamivudine; Male; Middle Aged; Mycophenolic Acid; Pneumonia, Pneumocystis; Prednisolone; Raltegravir Potassium; RNA, Viral; SARS-CoV-2; Tacrolimus; Trimethoprim, Sulfamethoxazole Drug Combination

Pediatric heart transplantation is a surgical therapy for dilated cardiomyopathy and for complex congenital heart defects with low pulmonary artery resistance. However, it is still discussed as controversial because of uncertain long-term results. We report our experience with pediatric heart transplantation in a heterogeneous population.. Since 1988, 50 heart transplants were performed in 47 patients (30 with dilated cardiomyopathy, 17 with congenital heart disease). Mean age was 9.4 +/- 6.9 years (range, 4 days to 17.9 years). Twenty-three patients had a total of 36 previous operations. Clinical outcome was evaluated retrospectively.. Perioperative mortality was 6% due to primary graft failure. Late mortality (12%) was caused by acute rejection (n = 2), pneumonia (n = 2), intracranial hemorrhage (n = 1), and suicide (n = 1). Mean follow-up was 5.24 +/- 3.6 years. Actuarial 1, 5, and 10 year survival was 86%, 86%, and 80% and improved significantly after 1995 (92% [1 year]; 92% [5 years]). There was no significant difference between patients with dilated or congenital heart disease (1 year: 86% vs 82%; 5 years: 83% vs 74%; 10 years 83% vs 74%; p = 0.62). Three patients with therapy resistant acute or chronic rejection and assisted circulation underwent retransplantation and are alive. Freedom from acute rejection after 5 years was 40% with primary cyclosporine immunosuppression regime and 56% with tacrolimus. Since the introduction of mycophenolate mofetil, freedom from acute rejection increased to 62%. All survivors are at home and in good cardiac condition.. Pediatric heart transplantation is the treatment of choice for end-stage dilated cardiomyopathy as for congenital heart disease with excellent clinical midterm results. It is a valid alternative to reconstructive surgery in borderline patients. However, further follow-up is necessary to evaluate the long-term side effects of immunosuppressants.

Topics: Adolescent; Antiviral Agents; Bacterial Infections; Cardiomyopathy, Dilated; Child; Child, Preschool; Cyclosporine; Cytomegalovirus Infections; Extracorporeal Membrane Oxygenation; Female; Follow-Up Studies; Ganciclovir; Germany; Graft Rejection; Heart Defects, Congenital; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Immunosuppressive Agents; Life Tables; Lymphoma, Non-Hodgkin; Male; Mycophenolic Acid; Pneumonia, Pneumocystis; Postoperative Complications; Reoperation; Retrospective Studies; Survival Analysis; Survival Rate; Tacrolimus; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Vascular Resistance; Virus Diseases

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

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

At the Tor Vergata University of Rome, ab initio calcineurin inhibitor-based monotherapy immunosuppression (IS) is the standard of treatment after liver transplantation (LT). As the net state of IS determines the onset of Pneumocystis jirovecii pneumonia (PCP), we hypothesized that, in the presence of weak impairment of the immune function, as determined by the above-mentioned IS, the host is not overexposed to the risk for PCP and consequently the specific anti-PCP prophylaxis is unnecessary. In a single-cohort descriptive study, we retrospectively investigated the incidence of PCP in 203 LT patients who did not receive anti-PCP prophylaxis because they were under monotherapy IS. The primary endpoint of the study was the incidence of PCP during the first 12 months following LT; secondary endpoints were the incidence of acute rejection requiring additional IS and of CMV infection. No cases of PCP were recorded. The incidence of CMV and acute rejection was 3.9% and 0.9%, respectively. Our data suggest that monotherapy IS after LT may nullify the risk for PCP even in the absence of any specific prophylaxis.

Topics: Adolescent; Adult; Aged; Calcineurin Inhibitors; Cyclosporine; Female; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Incidence; Liver Transplantation; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Risk; Tacrolimus; Treatment Outcome; Young Adult

Topics: Humans; Immunosuppressive Agents; Kidney Transplantation; Pneumonia, Pneumocystis; Tacrolimus

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

Everolimus reduces the incidence of cardiac-allograft vasculopathy (CAV) and is less renally toxic than are calcineurin inhibitors (CNIs). We evaluated the safety of CNI-free everolimus for post-heart transplant (HTx) patients.. We retrospectively reviewed the records of 36 consecutive patients who had undergone an HTx between January 2006 and December 2013 in National Cheng Kung University Hospital. All patients initially had been treated with the standard tacrolimus regimen. The Study group-12 patients with CAV, renal impairment, or a history of malignancy-were switched from tacrolimus to everolimus. The Control group consisted of 19 patients who remained on the standard regimen. The target everolimus trough concentration was 8-14 ng/mL. The primary outcome was survival, and the secondary outcomes were bacterial, viral, fungal, and other infections; Pneumocystis jirovecii pneumonia (PJP); and rejection (≥2R).. During a 53.3±25.6-month follow-up, the survival rate, rejection rate, and number of infections, except for PJP, were not significantly different between the two groups. In the Study group, 6 patients were diagnosed with PJP 33±18.2 months after switching. None of the Control group patients were diagnosed with PJP during follow-up.. A high-dose CNI-free everolimus maintenance regimen might yield a higher incidence of post-transplantation PJP.

Topics: Adult; Calcineurin Inhibitors; Everolimus; Female; Follow-Up Studies; Heart Transplantation; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Survival Analysis; Tacrolimus; Taiwan

After an outbreak of Pneumocystis pneumonia (PCP) in our nephrology unit, dapsone was used as the second-line chemoprophylactic agent. Dapsone is the most common cause of drug-induced methemoglobinemia (MHb). Its prevalence is poorly described in the renal transplant population. Because dapsone is excreted by the kidneys, we hypothesized that the rate of MHb in these patients would be higher than previously reported. We aimed to describe the demographics, risk factors, and presenting features of MHb in these renal transplant patients.. Twenty-six transplant recipients commenced on dapsone for chemoprophylaxis against PCP from February to September 2011. All patients had normal glucose-6-phosphate dehydrogenase levels before treatment. Characteristics of patients with MHb were compared with those of the rest of the cohort to determine potential risk factors.. Twelve (46%) patients developed MHb (levels 6.4 ± 4.1%). Six (50%) of the patients with MHb were asymptomatic on presentation. Cases had a mean drop in hemoglobin of 19 ± 7%. MHb led to five admissions (median length of stay 5 days, range 1-10 days). MHb level showed a strong correlation with the length of stay (correlation coefficient 0.762, P = 0.002).. This is the highest reported prevalence of MHb, to our knowledge, in patients receiving dapsone, and its use led to significant hospitalization in this population. This study raises concerns about the use of dapsone as chemoprophylaxis in renal transplant recipients.

Topics: Adult; Aged; Anti-Infective Agents; Azathioprine; Cohort Studies; Cyclosporine; Dapsone; Female; Glomerular Filtration Rate; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Length of Stay; Male; Methemoglobinemia; Middle Aged; Mycophenolic Acid; Pneumonia, Pneumocystis; Prednisolone; Prevalence; Regression Analysis; Risk Factors; Tacrolimus

Tacrolimus is an immunosuppressive drug used to prevent acute rejection following organ transplantation and to treat autoimmune disease. Tacrolimus is usually prescribed in such situation at a dose of 3.0 mg/day. Pneumocystis pneumonia induced by this dose of tacrolimus has been reported in many cases; however, we encountered a rare case of Pneumocystis pneumonia induced by low-dose tacrolimus and methylprednisolone.. We herein report the case of an 82-year-old Asian Japanese female with rheumatoid arthritis and Pneumocystis pneumonia who was being treated with low-dose tacrolimus and low-dose methylprednisolone therapy. She was diagnosed with rheumatoid arthritis at 52 years of age and was administered oral low-dose methylprednisolone and salazosulfapyridine. Her condition had been stable under this treatment for 30 years. However, her arthralgia worsened three months before admission. The salazosulfapyridine was changed to tacrolimus (0.5 mg/day) by her physician, and her arthralgia almost completely disappeared. She was admitted to our hospital for Pseudomonas pneumonia, and her symptoms improved almost completely with intravenous ceftazidime therapy. However, on the 14th day of admission, she developed acute respiratory failure due to Pneumocystis pneumonia and died on the 17th day of admission in spite of adequate treatment.. Our report highlights the importance of providing prompt prevention, diagnosis and treatment of Pneumocystis pneumonia in rheumatoid arthritis patients under tacrolimus and low-dose methylprednisolone therapy.

Topics: Aged; Aged, 80 and over; Arthritis, Rheumatoid; Dose-Response Relationship, Drug; Female; Humans; Methylprednisolone; Pneumonia, Pneumocystis; Tacrolimus

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

To report 3 separate cases of wound dehiscence in liver transplant recipients receiving sirolimus for immunosuppressive therapy.. Three patients who had received liver transplants experienced a delay in wound granulation and healing after being placed on an immunosuppressive regimen containing sirolimus and steroids. Each patient was admitted and treated for wound dehiscence, at which time sirolimus was discontinued. When other immunosuppressive agents were substituted for sirolimus, each incisional wound granulated and closed without complication.. Sirolimus is an important adjunctive immunosuppressant used to prevent acute rejection episodes in patients who have undergone transplant, particularly when nephrotoxic effects from first-line calcineurin inhibitors become problematic. The unique ability of sirolimus to inhibit smooth muscle cell proliferation and intimal thickening by blocking important growth factors may subsequently become a significant feature to prevent the development of chronic rejection. Theoretically, by this same mechanism, sirolimus may play a role in forestalling wound healing and may even promote dehiscence.. These case reports describe patients who underwent liver transplant who developed wound dehiscence possibly secondary to sirolimus therapy. Although the cases were complicated by acute rejection, wound infections, and comorbidities, wound granulation and healing began after discontinuation of sirolimus. Substitution with another immunosuppressant may be necessary for patients who experience wound dehiscence after transplant.

Topics: Adult; Anti-Inflammatory Agents; Cyclosporine; Female; Graft Rejection; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Pneumonia, Pneumocystis; Prednisone; Reoperation; Sirolimus; Surgical Wound Dehiscence; Tacrolimus

Topics: Animals; Dexamethasone; Humans; Immunosuppressive Agents; Mycophenolic Acid; Pneumonia, Pneumocystis; Rats; Sirolimus; Tacrolimus

We report on a case of bronchiolitis obliterans organizing pneumonia (BOOP) associated with Pneumocystis carinii pneumonia (PCP) after liver transplantation and tacrolimus based immunosuppression. Radiologically, bilateral diffuse interstitial shadowing and patchy alveolar infiltrates developed after switching the patient from cyclosporin A to tacrolimus for persistent rejection. Bronchoalveolar lavage (BAL) fluid showed inflammatory cells but no pathogenic organisms. Open lung biopsy revealed BOOP with granulomatous PCP. Thus, even in the case of negative BAL the possibility of an atypical P. carinii infection has to be considered for differential diagnosis of pneumonia in immunocompromised patients after organ transplantation. The combination of BOOP with PCP after liver transplantation and tacrolimus medication has not been reported previously.

Topics: Cryptogenic Organizing Pneumonia; Diagnosis, Differential; Humans; Immunocompromised Host; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Pneumonia, Pneumocystis; Tacrolimus

Pneumocystis carinii pneumonia (PcP) in immunocompromised patients is suggested if the following symptoms develop: dyspnea, fever, and interstitial infiltrates on chest x-ray. We observed a significant blood eosinophilia in kidney recipients with PcP under immunosuppressive treatment with tacrolimus.. Blood eosinophil counts of kidney recipients under immunosuppression with tacrolimus suffering from PcP were compared to eosinophil counts of patients without evidence of PcP and to patients showing PcP under immunosuppression with cyclosporine.. PcP-positive patients treated with tacrolimus showed a significantly higher blood eosinophil count compared to PcP-positive patients treated with cyclosporine (P=0.01), and to patients under immunosuppression with tacrolimus without PcP, respectively (P=0.006). Eosinophilia preceded the time of a definitive PcP diagnosis by bronchoalveolar lavage and decreased after successful treatment.. An increasing blood eosinophil count can be an indicator of P. carinii pneumonia in patients under immunosuppressive therapy with tacrolimus.

Topics: Adult; Aged; Azathioprine; Cyclosporine; Drug Therapy, Combination; Eosinophilia; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Leukocyte Count; Male; Middle Aged; Pneumonia, Pneumocystis; Prednisolone; Retrospective Studies; Tacrolimus

An 8-month-old child with an immunodeficiency disorder characterized by abnormal lymphocyte function and by low IgG and IgA levels had combined liver and small bowel transplantation under tacrolimus and steroid immunosuppression for the treatment of short gut syndrome and hepatic cirrhosis. The patient developed an early postoperative episode of Pneumocystis carinii pneumonia, and a subsequent surgical complication, prompting discontinuance of tacrolimus. A skin rash eventually shown to be graft-versus-host disease (GVHD) developed in the flank on the 12th post-transplant day and gradually became generalized. Peritonitis, sepsis, multisystem organ failure including the liver allograft led to death on the 23rd post-operative day. The mechanisms leading to post-transplant GVHD under the specific circumstances in this case are discussed.

Topics: Exanthema; Fatal Outcome; Female; Glucocorticoids; Graft vs Host Disease; Humans; IgA Deficiency; IgG Deficiency; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Infant; Intestine, Small; Ischemia; Liver; Liver Cirrhosis; Liver Transplantation; Lymphocytes; Methylprednisolone; Multiple Organ Failure; Peritonitis; Pneumonia, Pneumocystis; Sepsis; Short Bowel Syndrome; Tacrolimus

The incidence and potential risk factors of Pneumocystis carinii pneumonia (PCP) in our population of renal transplant recipients were analyzed retrospectively. Of 1427 patients who received transplants between January 1986 and June 1994, 1192 were evaluated. Four different immunosuppressive regimens were applied: (1) cyclosporine (CsA) + prednisolone (Pred), (2) CsA + azathioprine (Aza, 2 mg/kg/day) + Pred, (3) CsA + Aza + antithymocyte globulin, and (4) (after December 1, 1993, European multicenter trial) FK506 + Aza (1 mg/kg/day) + Pred. No prophylaxis against PCP was performed. Before December 1, 1993, three PCPs in 494 patients on protocol 2 or 3 occurred (0.6%). Afterward, seven PCPs in 77 patients occurred (9%): three in 38 patients on protocol 2 (7.8%) and four in 28 patients on protocol 4 (14.3%). Comparing patients with PCP on CsA and FK506, the mean Aza dose was 2.40 and 1.32 mg/kg/day, five and two patients received additional steroids, antibody treatment was used in three and no patients, and CMV infections occurred in five and two patients, respectively. The incidence of PCP with a moderate CsA-based immunosuppressive regimen is low and seems to occur only in cases of additional immunosuppressive cofactors. Despite a general increase of PCP, its incidence was highest in patients on FK506 with fewer immunosuppressive cofactors. Thus, prophylaxis against PCP after renal transplantation should be performed, if not in every renal transplant recipient, at least in case of treatment with additional steroids, antibodies, or FK506.

Topics: Adult; Female; Graft Survival; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Male; Middle Aged; Pneumonia, Pneumocystis; Postoperative Complications; Retrospective Studies; Tacrolimus