mycophenolic-acid and Bacterial-Infections

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

Whether the intensity of the conditioning regimen affects febrile neutropenia (FN) and severe bacterial infections (SBIs) is not well established. We analyzed the risk factors (RFs) for the development of FN and SBI in the first 100d post-transplant in 195 consecutive adult recipients of a reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC-allo).. The RIC regimens consisted of fludarabine plus melphalan (62%) or busulphan (38%) (FluMel or FluBu). SBIs include pneumonia, urinary tract infections, and bacteremia.. FN occurred in 141 patients (72%), always in the first 30d post-allo-RIC. However, a SBI occurred in only 27 patients (14%) during this early post-transplant period (

Topics: Adult; Bacterial Infections; Busulfan; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Melphalan; Middle Aged; Mucositis; Mycophenolic Acid; Myeloablative Agonists; Neutropenia; Retrospective Studies; Risk Factors; Time Factors; Transplantation Conditioning; Transplantation, Homologous

Mycophenolate sodium (EC-MPS) has been shown to be as effective and as safe as mycophenolate mofetil (MMF) in renal transplant patients. Nevertheless, compared to MMF its use in liver transplant patients has been limited. The purpose of this study was to analyze the efficacy of EC-MPS as a primary immunosuppressant or as a replacement for MMF in liver transplant patients. Ninety among 470 liver transplant recipients were receiving or had added an antimetabolite to their immunosuppressant therapy. The most common reason for this change was renal dysfunction (47.8%) or diabetes (32.2%). EC-MPS was started at a median of 30 months after liver transplantation. The mean administered daily dose was 720 mg/d. At least one gastrointestinal symptom was reported by 25 patients. Abdominal pain (16.6%) and diarrhea (14.5%) were the most frequent. EC-MPS had to be discontinued in two patients, while six others required dose reduction to resolve the symptoms. Hematological adverse events were infrequent: three patients had leukopenia and one, anemia, all of which responded to dosage reduction. There was a creatinine reduction within 6 months of drug commencement and maintenance of the lower creatinine levels at 1 year among patients who began EC-MPS for renal dysfunction. Serum low-density lipoprotein cholesterol and triglyceride levels were significantly lower among patients on EC-MPS than on MMF. In conclusion, EC-MPS appears to have a similar efficacy and safety profile as MMF in liver transplant patients. Hematological and gastrointestinal adverse events were infrequent; seldom had the drug to be discontinued.

Topics: Bacterial Infections; Female; Gastrointestinal Diseases; Humans; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Tablets, Enteric-Coated

The aim of this study was to investigate infectious complications in renal transplant recipients (RTRs) receiving mycophenolate mofetil (MMF) for prevention of acute transplant rejection. A group of RTRs (n = 47) receiving 1.0-2.0 g/day of MMF with cyclosporine A (CsA) and prednisolone to maintain immunosuppression was compared with a group (n = 47) taking triple immunosuppressive therapy including azathioprine. In both groups the etiology and incidence of infections were evaluated. During 2 years post-transplant, various infections developed in 72.3% of patients who received MMF and in 93.6% of those who received azathioprine. The incidence of viral infections was 53.2% in the MMF group and 59.6% in the azathioprine group and the incidence of bacterial infection was 55.3% and 70.2%, respectively There were two cases of active tuberculosis in the azathioprine group and one in the MMF group. MMF 1.0-2.0 g/day does not increase infection rates in RTRs compared with azathioprine.

Topics: Azathioprine; Bacterial Infections; Cyclosporine; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Prednisolone; Virus Diseases

Differences in the incidence, etiology, type, and outcome of infections occurring during the first 6 months after transplantation were evaluated in two consecutive cohorts of kidney recipients who received immunosuppressive regimens based on either azathioprine (plus antilymphocyte globulin, cyclosporine A, and prednisone) (ATG-AZA cohort) or mycophenolate-mofetil (plus cyclosporine A and prednisone) (MMF cohort). The overall incidence of infections in the two cohorts was similar (0.99+/-1.06 infections/patient in the MMF cohort and 1.04+/-0.99 in the ATG-AZA cohort, P=0.3), as was the incidence of bacterial and fungal infections. In patients who received mycophenolate, cytomegalovirus disease occurred at a higher incidence (0.3+/-0.54 vs. 0.1+/-0.34 episodes/patient, P=0.005) and affected the upper gastrointestinal tract more frequently (0.21+/-0.48 vs. 0.025+/-0.16 episodes of cytomegalovirus ulcerative esophagitis, gastritis, or duodenitis per patient; P=0.001). A nonsignificant trend toward a higher recipient survival for patients receiving mycophenolate was noted (100% vs. 95%, P=0.07). In multivariate analysis, the following factors were independently associated with a higher risk of cytomegalovirus disease: the serostatus R-/D+ (seronegative recipients who received a kidney from a seropositive donor) (RR=35.7 [95%CI, 7.4-166.7]), treatment with mycophenolate (RR=10.4 [95%CI, 2.7-38.4]), and the development of any episodes of acute rejection (RR=10.1 [95%CI, 2.5-41.6]). These data show that kidney recipients receiving mycophenolate have a higher incidence of cytomegalovirus disease, mainly affecting the upper gastrointestinal tract, compared to those receiving azathioprine-based immunosuppression.

Topics: Adult; Azathioprine; Bacterial Infections; Cohort Studies; Drug Therapy, Combination; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Mycoses; Opportunistic Infections; Prospective Studies; Treatment Outcome; Virus Diseases

In the past, enteric drainage or the omission of induction immunotherapy has been shown to be predictive of suboptimal outcomes of simultaneous pancreas-kidney (SPK) transplantation. We have reassessed the need for bladder drainage and induction immunotherapy to optimize the outcome of SPK transplantation.. One hundred consecutive recipients of SPK transplants who received mycophenolate mofetil and tacrolimus immunosuppression were studied. The first 50 recipients had bladder-drained pancreas allografts and received induction immunotherapy. The results were compared with the next 50 recipients who had enteric-drained pancreas allografts, which included a subgroup (n = 17 patients) who were randomized to receive no induction immunotherapy.. The 1-year actuarial patient, kidney, and pancreas survival rates in the bladder-drainage group were 98.0%, 94.0%, and 94.0%, respectively. The 1-year actuarial patient, kidney, and pancreas survival rates in the enteric-drainage group were 96.8%, 96.8%, and 89.4%, respectively. In the enteric-drainage group, the incidence of rejection at 1 year was 6.1% in recipients who received induction therapy versus 23.5% in recipients who did not receive induction therapy. The average number of readmissions per recipient was 1.8 in the bladder-drainage group versus 0.9 in the enteric-drainage group.. Primary enteric drainage of the pancreas allograft in recipients of SPK transplantation is the preferred surgical technique in the tacrolimus/mycophenolate mofetil era.

Topics: Adult; Bacterial Infections; Drainage; Female; Graft Rejection; Graft Survival; Humans; Hypertension, Renal; Immunosuppressive Agents; Incidence; Intestines; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Pancreas Transplantation; Patient Readmission; Postoperative Complications; Survival Analysis; Tacrolimus; Treatment Outcome; Urinary Bladder

Immunoglobulin replacement therapy is recommended in case of severe hypogammaglobulinemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the supposed increased risk of infection in case of hypogammaglobulinemia has not been confirmed in allo-HSCT. In this study, we assessed the relationship between the gamma globulin level and the risk of infection during the 100 days following the allo-HSCT.. We gathered the weekly laboratory tests from day 7 to day 100 of 76 allograft patients, giving a total of 1 044 tests. 130 infections were documented clinically, by imaging, or microbiologically.. Average gamma globulin levels between D-7 and D100 did not differ between patients with or without infection (642 ± 232 and 671 ± 246 mg/dL, respectively, P = .65). Gamma globulin level <400 mg/dl was not associated with the occurrence of infection between the test studied and the next one (aOR 1.33 [0.84-2.15], P = .24). The gamma globulin level was not predictive of bacterial or fungal infections (AUC 0.54 [95%CI: 0.47-0.61]) nor of viral reactivations (AUC 0.51 [95%CI: 0.43-0.60]).. This confirmed that the humoral deficiency is a minor part of the immune deficiency in the 100 days post-transplant. This questions the relevance of the indications of immunoglobulin substitution during this period.

Topics: Aged; Bacterial Infections; Cyclosporine; Female; gamma-Globulins; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulins, Intravenous; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Leukemia; Lymphoma; Male; Middle Aged; Mycophenolic Acid; Mycoses; Myeloablative Agonists; Myelodysplastic Syndromes; Opportunistic Infections; Prognosis; ROC Curve; Transplantation Conditioning; Transplantation, Homologous; Virus Activation

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited response to currently available therapies. Alveolar type II (ATII) cells act as progenitor cells in the adult lung, contributing to alveolar repair during pulmonary injury. However, in IPF, ATII cells die and are replaced by fibroblasts and myofibroblasts. In previous preclinical studies, we demonstrated that ATII-cell intratracheal transplantation was able to reduce pulmonary fibrosis. The main objective of this study was to investigate the safety and tolerability of ATII-cell intratracheal transplantation in patients with IPF.. We enrolled 16 patients with moderate and progressive IPF who underwent ATII-cell intratracheal transplantation through fiberoptic bronchoscopy. We evaluated the safety and tolerability of ATII-cell transplantation by assessing the emergent adverse side effects that appeared within 12 months. Moreover, pulmonary function, respiratory symptoms, and disease extent during 12 months of follow-up were evaluated.. No significant adverse events were associated with the ATII-cell intratracheal transplantation. After 12 months of follow-up, there was no deterioration in pulmonary function, respiratory symptoms, or disease extent.. Our results support the hypothesis that ATII-cell intratracheal transplantation is safe and well tolerated in patients with IPF. This study opens the door to designing a clinical trial to elucidate the potential beneficial effects of ATII-cell therapy in IPF.

Topics: Adrenal Cortex Hormones; Aged; Alveolar Epithelial Cells; Anti-Infective Agents; Bacterial Infections; Bronchoscopy; Cell Transplantation; Disease Progression; Female; Forced Expiratory Volume; Ganciclovir; Graft Rejection; Humans; Idiopathic Pulmonary Fibrosis; Immunosuppressive Agents; Leucovorin; Male; Middle Aged; Mycophenolic Acid; Mycoses; Nystatin; Pulmonary Diffusing Capacity; Tacrolimus; Trachea; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Valganciclovir; Virus Diseases; Vital Capacity; Walk Test

Leukopenia is a common manifestation of SLE. Addition of immunosuppressive therapy in a SLE patient who is already leukopenic is a clinical concern. It could worsen leukopenia, increase the risk of infection, or both. The aim of this study was to analyze the immediate effect of mycophenolate mofetil on the white blood cell count and the rate of infection in SLE patients. Two hundred and forty-four patients within the Hopkins Lupus Cohort who were newly started on mycophenolate mofetil were included in the study. The white blood cell count and interval infection history on the day mycophenolate mofetil was started were compared with the white blood cell count and interval infection history at the next visit. The study was based on 244 patients who began taking mycophenolate mofetil in the cohort. The study population included 47 % African Americans, 44 % Caucasians, and 9 % other ethnicities. There was a slight but not statistically significant increase in the white blood cell count (6.63 vs. 7.01), after starting mycophenolate mofetil. Patients with a baseline white blood cell count <3000/mm(3) did have a statistically significant increase in the white blood cell count after starting mycophenolate mofetil (2.57 vs. 5.13, P = 0.0047). We also found a statistically significant increase in the risk of bacterial infection (but not viral infection) after starting mycophenolate mofetil (4 vs. 9 %, P = 0.0036). Leukopenia does not worsen with mycophenolate mofetil. However, mycophenolate mofetil appears to slightly increase the rate of bacterial (but not viral) infection.

Topics: Adult; Aged; Bacterial Infections; Female; Humans; Immunosuppressive Agents; Leukocyte Count; Leukocytes; Leukopenia; Lupus Erythematosus, Systemic; Male; Middle Aged; Mycophenolic Acid; Virus Diseases

BACKGROUND Mycophenolic acid (MPA) prodrugs are anti-proliferative immunosuppressive agents commonly used after organ transplantation. Although they are generally well tolerated by patients, adverse effects may occur. It is postulated that MPA metabolites could also contribute to these adverse effects. MATERIAL AND METHODS The objective of this study was the assessment of concentrations of total MPA and its metabolites, phenyl glucuronide (MPAG), acyl glucuronide (AcMPAG) and glucoside (GluMPA), using liquid chromatography combined with mass spectrometry (LC/MS/MS) in two groups: kidney transplant recipients and liver transplant patients. Associations of MPA and its metabolites with adverse effects were analyzed. RESULTS The study group consisted of 211 recipients of liver or kidney transplants who received immunosuppressive therapy, including MPA prodrugs. Multivariant analysis showed a positive influence of MPA on gastroenterotoxicity in kidney transplant recipients. In liver patients, gastroenterotoxicity was associated with lower MPAG concentrations. A positive influence of AcMPAG on bacterial infections in liver transplant patients was observed. In liver transplant recipients, a positive influence of MPA and a negative influence of GluMPA levels on the PLT count were revealed. MPA and its metabolites did not influence the hemoglobin levels in both groups. There were no significant relationships among MPA, its metabolites and WBC counts. CONCLUSIONS In kidney transplant recipients, total MPA trough concentration is associated with gastroenterotoxicity and its monitoring could have important role in management of gastrointestinal complications. The quantification of AcMPAG in liver recipients receiving MPA may be helpful in avoiding bacterial infections. GluMPA seems to have a toxic effect on thrombopoiesis.

Topics: Adult; Bacterial Infections; Cyclosporine; Female; Glucosides; Glucuronides; Humans; Immunosuppressive Agents; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Tacrolimus; Transplant Recipients

Several studies have suggested an association between post-transplant immunoglobulin (Ig) levels and the development of infection in solid organ transplantation. We therefore conducted exploratory analyses of potential factors associated with bacterial infection/sepsis after living-donor liver transplantation (LDLT).. Blood samples from 177 recipients who received primary LDLT between September 1999 and November 2011 were available for study. Hypogammaglobulinemia was defined as having at least 1 IgG level <650 mg/dL within 7 days after LDLT. Risk factors for developing post-transplant bacterial infection and sepsis within 3 months after LDLT were analyzed.. Fifty (28.2%) recipients experienced bacterial infection within 3 months of LDLT. Eighty-four (47.5%) recipients had hypogammaglobulinemia, although no recipients had hypogammaglobulinemia before LDLT. Hypogammaglobulinemia, undergoing hepaticojejunostomy, and portal pressure at closure >15 mmHg were independent risk factors for developing bacterial infection within 3 months of LDLT (P < 0.0001 P = 0.0008, and P = 0.011, respectively). The odds ratio (OR) and confidence interval (CI) for hypogammaglobulinemia were 4.79 and 2.27-10.7, respectively. Twenty-four (13.6%) recipients developed bacterial sepsis within 3 months. Hypogammaglobulinemia, operative time >14 h, model for end-stage liver disease score >15, and no mycophenolate mofetil use were independent risk factors for developing bacterial sepsis (P = 0.009, P = 0.001, P = 0.003, and P = 0.005, respectively). The OR and CI for hypogammaglobulinemia were 3.83 and 1.38-12.0, respectively.. Hypogammaglobulinemia within 7 days of LDLT was a significant risk factor for post-transplant bacterial infection and sepsis.

Topics: Adult; Agammaglobulinemia; Anastomosis, Surgical; Bacterial Infections; End Stage Liver Disease; Female; Hepatic Duct, Common; Humans; Hypertension, Portal; Immunoglobulin G; Immunosuppressive Agents; Jejunum; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Operative Time; Retrospective Studies; Risk Factors; Sepsis; Severity of Illness Index; Time Factors

The role of therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) in kidney transplant recipients (KTRs) is not clear. We performed a prospective cohort study to evaluate the efficiency of MPA TDM in the Chinese population.. A total of 183 living-related KTRs were studied; 101 KTRs received controlled-dose mycophenolate mofetil (MMF) (the CD group), and 82 patients received fixed-dose MMF (the FD group). MPA exposure was measured at days 3, 7, 14, and 30 in the CD group, and at day 30 in the FD group. The primary endpoint was treatment failure (a composite of acute rejection, graft loss, death, or MMF discontinuation) at 12 months post transplantation.. In the CD group, with a starting MMF dose of 2 g/day, approximately 35% of patients had high MPA levels, which were >60 mg × h/L, and mean MPA levels were 59.17 mg × h/L and 61.38 mg × h/L for the CD and FD groups, respectively (P = 0.588). After adjusting MMF dose, MPA exposures in the CD group at day 30 were lower than those in the FD group at day 30 (54.06 vs. 61.38, P = 0.004). At month 12, the CD group had fewer infections (16.8% vs. 31.7%, P = 0.018) with no difference in treatment failure, acute rejection, diarrhea, or anemia.. KTRs can benefit from short-term TDM of MPA in reducing infection, without increasing acute rejection.

Topics: Adult; Area Under Curve; Bacterial Infections; China; Drug Monitoring; Female; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Longitudinal Studies; Male; Mycophenolic Acid; Mycoses; Prospective Studies; Survival Rate; Time Factors; Treatment Failure; Young Adult

To investigate the factors in association with colorectal disorders in adult renal transplant recipients.. A retrospective cohort study was carried out with clinical, microbiological and management data regarding diarrhea in 513 renal transplant recipients from Jan. 2007 to Dec. 2012.. Of the 513 patients, 118(23.00%) with no history of ulcerative colitis, were found to have diarrhea after kidney transplantation. In the 118 patients, diarrhea was probably caused by administration of immunosuppressive agents in 65 cases (55.08%), in 30 cases (25.42%) diarrhea was antibiotics associated, and in 23 cases (19.49%) it was due to infections, including bacterial, fungal and viral infections. Diarrhea occurred soon after transplantation in most cases. Of the 118 patients, the symptom of diarrhea occurred in the first 1 month in 84 cases (71.19%), and in the next 5 months in 16 cases (13.56%), and the other 18 cases (15.05%) occurred after 180 days after transplantation. Of the 118 patients, 84 cases (71.19%) were relieved or cured after proper diets, the symptomatic therapy or the adjust meat of the doses of immunosuppressive agents: 18 cases (15.25%) needed to use or adjust the antibiotics , 16 cases (13.56%) had to stop mycophenolate mofetil and convert to other drugs.. Immunosuppressive agents, antibiotics and infection are the common causes of diarrhea after kidney transplantation. The outcome is good with appropriate conservative management.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Child; Cyclosporine; Cytomegalovirus Infections; Diarrhea; Dose-Response Relationship, Drug; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Mycoses; Retrospective Studies; Tacrolimus; Young Adult

Current immunosuppressive therapies and protocols have led to significant improvements in early patient and graft survival rates following kidney transplantation. Whether induction therapies such as rabbit anti-thymocyte globulin (rATG) contribute to these improved results remains controversial. Full-dose rATG induction therapy (7-10 mg/kg) has been associated with increased morbidity, which may be especially true in a high-risk population such as the elderly. Therefore, we studied the efficacy and tolerability of a low-dose rATG induction strategy in 45 older recipients (>65 years) compared to 45 concurrently transplanted younger patients (<65 years). Both groups received a similar low-dose of rATG induction therapy (older: 2.96±1.29 vs younger: 3.2±2.11 mg/kg). All patients were maintained on a calcineurin inhibitor, mycophenolic acid, and low-dose prednisone (5 mg/d). To date, none of the older patients experienced acute rejection, whereas one younger patient had an acute rejection episode. Initial hospital stays were equal (older: 7.8±3.2 vs younger: 7.5±4.4 days, P=.35). Within the first 6 months, nine older patients required rehospitalization compared to 15 younger patients (P=.15). Bacterial infections in older and younger recipients were equal including wound (4 vs 0), urine (20 vs 15), lung (1 vs 1), and skin (0 vs 2), respectively. There were two BK viral infections in older patients, whereas there were three viral infections, two cytomegalovirus cases, and one Herpes zoster case in younger patients. Calculated 6-month glomerular filtration rate was equal in both groups (older: 55.7±18.5 vs younger: 52.7±18.5 mL/min). Three-year patient and graft survival rates were equivalent for older and younger patients (86.6% vs 97.6%, respectively). In conclusion, low-dose rATG induction therapy is safe and effective in patients older than 65. When compared to younger patients, low-dose rATG leads to equivalent graft survival and function without incurring excess morbidity in the older population.

Topics: Age Factors; Aged; Animals; Antilymphocyte Serum; Bacterial Infections; Calcineurin Inhibitors; Case-Control Studies; Female; Glomerular Filtration Rate; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Patient Readmission; Prednisone; Rabbits; Random Allocation; Retrospective Studies

Despite significant improvements in renal transplantation (RTX), certain basic issues remain unresolved such as the routine use of perioperative antibiotic prophylaxis (PAP). To address the need for PAP, we retrospectively evaluated the clinical course of 349 consecutive RTX patients who did not receive any PAP except for Bactrim. Of the 349 transplant recipients, 77% received induction therapy with low-dose rabbit antithymocyte globulin (rATG) and the others were treated with basiliximab. All patients received triple immunosuppression with tacrolimus, mycophenolic acid, and prednisone. Seven patients (2%) developed wound infections. Wound infections were more common in obese and older patients. All wound infections were superficial and responded well to wound drainage and outpatient antibiotic therapy. Six patients (1.7%) experienced a urinary tract infection (UTI) within the first postoperative month. UTIs were more common in the patient with ureteral stent compared to nonstented patients (11.4% vs 0.3%, P<.001). No patient or graft was lost due to perioperative bacterial infections (PBI). Our study shows that despite many predisposing factors, PBI are rare following RTX even in the absence of PAP. Therefore, in order to avoid emergence of multiantibiotic-resistant pathogens, excessive costs, and antibiotic-related adverse events, we suggest that PAP should be used only in selected circumstances such as in recipients older than 60 or when the body mass index is greater than 35.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Anti-Bacterial Agents; Antibodies, Monoclonal; Antilymphocyte Serum; Bacterial Infections; Basiliximab; Body Mass Index; Child; Child, Preschool; Drug Resistance, Bacterial; Female; Humans; Immunosuppressive Agents; Infant; Infant, Newborn; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Prednisone; Rabbits; Recombinant Fusion Proteins; Retrospective Studies; Tacrolimus; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Neutropenic episodes in kidney transplant patients are poorly characterized. In this retrospective study, neutropenia was experienced by 112/395 patients (28%) during the first year posttransplant. The only factor found to be significantly associated with the occurrence of neutropenia was combined tacrolimus-mycophenolate therapy (p < 0.001). Neutropenic patients experienced more bacterial infections (43% vs. 32%, p = 0.04). Grade of neutropenia correlated with the global risk of infection. Discontinuation of mycophenolic acid (MPA) due to neutropenia was associated with an increased incidence of acute rejection (odds ratios per day 1.11, 95% confidence intervals 1.02-1.22) but not with reduced renal function at 1 year. The time from onset of neutropenia to MPA discontinuation correlated with the duration of neutropenia. Granulocyte colony-stimulating factor (G-CSF) administration was safe and effective in severely neutropenic kidney graft recipients, with absolute neutrophil count >1000/microL achieved in a mean of 1.5+/-0.5 days. Neutropenia is an important and frequent laboratory finding that may exert a significant influence on outcomes in kidney transplantation. As well as leading to an increased incidence of infection, it is associated with a higher rate of allograft rejection if MPA is discontinued for >6 days (p = 0.02). G-CSF accelerates recovery of neutropenia and may be a good therapeutic alternative for severely neutropenic patients.

Topics: Adult; Aged; Bacterial Infections; Drug Therapy, Combination; Female; Graft Rejection; Granulocyte Colony-Stimulating Factor; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Neutropenia; Retrospective Studies; Risk Factors; Tacrolimus

Graft-versus-host-disease (GVHD) is a complication of solid organ transplantation, most commonly of the small bowel or liver. Herein, we have presented a case of GVHD in a 27-year-old man who underwent an human leukocyte antigen (HLA) minor mismatch renal transplantation from his father. After the procedure, the patient presented with a fever, skin rash, and watery diarrhea. An allograft kidney biopsy demonstrated no sign of rejection; however, anti-A antibody was detected in plasma and progressive anemia was attributed to hemolytic anemia owing to a passenger lymphocyte syndrome. From those findings, we suspected that the clinical symptoms were caused by acute GVHD. An endoscopic biopsy of the colon revealed apoptotic cells consistent with the disease. We found reports of only 5 other GVHD cases after kidney transplantation. Several risk factors are associated with GVHD, such as transfer of graft lymphocytes, donor HLA homozygosity, and a relationship between recipient immunogenicity and immunosuppression. In this case, detection led to early diagnosis of donor-derived GVHD due to passenger lymphocyte syndrome. It is important keep GVHD in mind and to understand its risk factors as the mortality rate is high.

Topics: Acute Disease; Adult; Anemia, Hemolytic; Anti-Bacterial Agents; Anti-Inflammatory Agents; Bacterial Infections; Female; Graft vs Host Disease; HLA Antigens; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Methylprednisolone Hemisuccinate; Mycophenolic Acid; Pancreas Transplantation; Reoperation; Treatment Outcome

Studies of renal transplantation utilizing trough plasma level monitoring of mycophenolic acid (MPA) have shown inconsistent associations with toxicity and rejection. In this study, 5600 12-h trough MPA samples from 121 renal transplant recipients immunosuppressed with mycophenolate mofetil (MMF) and tacrolimus in a steroid sparing protocol (steroids for 7 days only) were sequentially analyzed. Higher MPA levels were associated with lower hemoglobin concentrations and anemia (hemoglobin <10 g/dL). Similarly, higher MPA levels were associated with lower total white cell counts and an increased incidence of leucopenia (total white cell count <4.0 x 10(9)/L). Hypoalbuminemia and renal impairment were also associated with hemotoxicity. MMF-associated diarrhea and viral infection were associated with higher MPA levels. Conversely, biopsy-proven acute rejection within the first month post-transplantation was associated with lower MPA levels. Anti-CD25 antibody induction was also associated with reduced rejection rates. No association was seen between MPA levels and platelet count, thrombocytopenia or bacterial infection. An MPA level of 1.60 mg/L early post-transplantation best discriminated patients with and without rejection, and an MPA level of 2.75 mg/L best discriminated patients with and without toxicity later post-transplantation.

Topics: Adult; Bacterial Infections; Bone Marrow; Diarrhea; Dose-Response Relationship, Drug; Drug Monitoring; Female; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Leukocyte Count; Leukopenia; Male; Middle Aged; Monitoring, Physiologic; Mycophenolic Acid; Platelet Count; Tacrolimus; Thrombocytopenia; Virus Diseases

A drug regimen including a calcineurin inhibitor (cyclosporine or tacrolimus) and prednisone has been the mainstay of maintenance immunosuppression in our renal transplant recipients for more than 10 years. After the introduction of mycophenolate mofetil (MMF), a new, potent immunosuppressant that may reduce the incidence of late rejection in renal transplant recipients, the immunosuppressive protocol in some recipients was changed to an MMF-based regimen. We sought to ascertain whether the addition of MMF lead to greater susceptibility to infectious complications.. Between May 1991 and November 2002, all renal transplant recipients who received a two-drug regimen initially for more than 6 months were changed to an MMF-based regimen. The study includes patients with functional grafts for more than 6 months thereafter. Differences in the incidence, etiology, and outcome of infections were compared during the non-MMF versus the MMF periods.. Eighty patients of mean age of 38.6 years (range 13 to 69) included 43 men and 37 women. The mean daily MMF dose was 663 mg/patient (range 250 to 1500 mg). The mean follow-up time of non-MMF period and MMF periods were 3.4 and 2.1 years, respectively. The overall incidence of infections in the two periods was similar (0.2 infections/patient in the non-MMF period and 0.25 infections/patient in the MMF period, P = .57). No mortality was associated with these infectious complications. In conclusion, addition of MMF, a more potent immunosuppressive protocol, did not increase the incidence of infections in stable renal transplant recipients initially treated with a two-drug regimen.

Topics: Bacterial Infections; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Incidence; Infections; Kidney Transplantation; Mycophenolic Acid; Retrospective Studies; Taiwan; Virus Diseases