Infection In Heart Transplantation Research Articles

A Clinical Model to Predict the Occurrence of Select High-risk Infections in the First Year Following Heart Transplantation.

Invasive infection remains a dangerous complication of heart transplantation (HT). No objectively defined set of clinical risk factors has been established to reliably predict infection in HT. The aim of this study was to develop a clinical prediction model for use at 1 mo post-HT to predict serious infection by 1 y. A retrospective cohort study of HT recipients (2000-2018) was performed. The composite endpoint included cytomegalovirus (CMV), herpes simplex or varicella zoster virus infection, blood stream infection, invasive fungal, or nocardial infection occurring 1 mo to 1 y post-HT. A least absolute shrinkage and selection operator regression model was constructed using 10 candidate variables. A concordance statistic, calibration curve, and mean calibration error were calculated. A scoring system was derived for ease of clinical application. Three hundred seventy-five patients were analyzed; 93 patients experienced an outcome event. All variables remained in the final model: aged 55 y or above, history of diabetes, need for renal replacement therapy in first month, CMV risk derived from donor and recipient serology, use of induction and/or early lymphodepleting therapy in the first month, use of trimethoprim-sulfamethoxazole prophylaxis at 1 mo, lymphocyte count under 0.75 × 103cells/µL at 1 mo, and inpatient status at 1 mo. Good discrimination (C-index 0.80) and calibration (mean absolute calibration error 3.6%) were demonstrated. This model synthesizes multiple highly relevant clinical parameters, available at 1 mo post-HT, into a unified, objective, and clinically useful prediction tool for occurrence of serious infection by 1 y post-HT.

Epidemiology, management, and clinical outcomes of extrapulmonary Mycobacterium abscessus complex infections in heart transplant and ventricular assist device recipients

Nontuberculous mycobacteria are emerging pathogens, yet data on the epidemiology and management of extrapulmonary nontuberculous mycobacteria infections in orthotopic heart transplantation (OHT) and ventricular assist device (VAD) recipients are scarce. We retrospectively reviewed records of OHT and VAD recipients who underwent cardiac surgery at our hospital and developed Mycobacterium abscessus complex (MABC) infection from 2013 to 2016 during a hospital outbreak of MABC linked to heater-cooler units. We analyzed patient characteristics, medical and surgical management, and long-term outcomes. Ten OHT patients and 7 patients with VAD developed extrapulmonary M. abscessus subspecies abscessus infection. The median time from presumed inoculation during cardiac surgery to the first positive culture was 106 days in OHT and 29 days in VAD recipients. The most common sites of positive cultures were blood (n = 12), sternum/mediastinum (n = 8), and the VAD driveline exit site (n = 7). The 14 patients diagnosed when alive received combination antimicrobial therapy for a median of 21 weeks, developed 28 antibiotic-related adverse events, and underwent 27 surgeries. Only 8 (47%) patients survived longer than 12 weeks after diagnosis, including 2 patients with VAD who experienced long-term survival after an explantation of infected VADs and OHT. Despite aggressive medical and surgical management, OHT and VAD patients with MABC infection experienced substantial morbidity and mortality.

Post-transplant absolute lymphocyte count predicts early cytomegalovirus infection after heart transplantation

Immunosuppressive therapy can decrease rejection episodes and increase the risk of severe and fatal infections in heart transplantation (HT) recipients. Immunosuppressive therapy can also decrease the absolute lymphocyte count (ALC), but the relationship between early post-transplant ALC and early cytomegalovirus (CMV) infection is largely unknown, especially in HT. We retrospectively analyzed 58 HT recipients who tested positive for CMV IgG antibody and received basiliximab induction therapy. We collected preoperative and 2-month postoperative data on ALC and CMV load. The CMV load > 1200 IU/mL was used as the cutoff value to define early CMV infection. Post-transplant lymphopenia was defined as an ALC of < 500 cells/μL at postoperative day (POD) #7. On POD #7, 29 (50.0%) patients had post-transplant lymphopenia and 29 (50.0%) patients did not. The incidence of CMV infection within 1 or 2 months of HT was higher in the post-transplant lymphopenia group than in the non-lymphopenia group (82.8% vs. 48.3%, P = 0.013; 89.7% vs. 65.5%, P = 0.028, respectively). ALC < 500 cells/μL on POD #7 was an independent risk factor for early CMV infection within 1 month of HT (odds ratio, 4.14; 95% confidence interval, 1.16–14.77; P = 0.029). A low ALC after HT was associated with a high risk of early CMV infection. Post-transplant ALC monitoring is simple and inexpensive and can help identify patients at high risk of early CMV infection.

A case series of novel coronavirus infection in heart transplantation from 2 centers in the pandemic area in the North of Italy

BackgroundLittle is known about the coronavirus SARS-CoV-2 disease (COVID-19) in solid organ transplanted patients. We here report a series of heart transplanted patients with COVID-19 from two centers of Italy.MethodsAll heart transplanted patients of Transplant Centers of Bergamo and Torino with a microbiologically confirmed SARS-CoV-2 infection were enrolled. Data collection included clinical presentation, laboratory and radiological findings, treatment and outcome. Follow-up was performed by visit or phone.ResultsFrom February to March 2020 twenty-six heart transplanted patients (age 62±12 years; 77% males; time from transplant 10±10 years; 69% with comorbidities) had a microbiologically confirmed COVID-19. The most frequent symptom was fever, followed by cough. Seventeen patients had a pneumonia, 8 of them severe pneumonia. Seven patients died (27%) and 17 (65%) were hospitalized. Discontinuation of immunosuppression was associated with death (71 vs 21%, p=0.02). Conversely, all patients receiving steroids survived (p<0.001). Patients who received heart transplantation during COVID-19 outbreak survived and no acute graft rejection occurred. Patients who died were older than survivors, had a longer time from transplant and a worse clinical presentation at diagnosis.The current regimen enabled the prolonged survival and function of orthotopic cardiac xenografts in altogether 6 of 8 baboons, of which 4 were now added. These results exceed the threshold set by the Advisory Board of the International Society for Heart and Lung Transplantation.ConclusionsCOVID-19 has a significant impact on long term heart transplanted patients. Conversely, SARS-CoV-2 infection seems to have a limited influence on more recent transplants. Our experience may suggest that heart transplantation programs can be maintained even during the pandemic phase if specific and tailored paths to prevent and to limit virus transmission are provided.

Monitoring cell-mediated immunity during immunosuppression reduction in heart transplant recipients with severe systemic infections.

Treatment for severe systemic infections in heart transplantation is reduction in immunosuppression while treating the infection. An assay that measures adenosine triphosphate production in activated lymphocytes (ImmuKnow® ) objectively monitors cellular immunity of transplant recipients. In this study, we used ImmuKnow® to adjust immunosuppression in heart transplant recipients with severe systemic infections. Heart transplant recipients were followed with ImmuKnow® at the time of biopsy and diagnosis of systemic infection. Patients who developed an infection were monitored by ImmuKnow® assay with adjustments in immunosuppression based upon the results of the assay. Maintenance immunosuppression was reinstituted when the ImmuKnow® increased to >225ng/mL of ATP. Two or more ImmuKnow® assays were performed in 80 patients. Thirteen patients developed severe systemic infections. ImmuKnow® mean value at the time of diagnosis of infection was 109±49.2ng/mL. Reduction in immunosuppression and treatment of infection resulted in normalization of ImmuKnow® level, resolution of infection, and no episodes of rebound rejection. Heart transplant recipients with severe systemic infections presented with a decreased ImmuKnow® , suggesting over immunosuppression. ImmuKnow® can be used as an objective measurement in withdrawing immunosuppression in heart transplant recipients with severe systemic infections.

Contraceptive vaccination for mares and its effects on cyclicity and estrous behavior

New biomarkers are necessary to improve detection of the risk of infection in heart transplantation. We performed a multicenter study to evaluate humoral immunity profiles that could better enable us to identify heart recipients at risk of severe infections.We prospectively analyzed 170 adult heart recipients at 8 centers in Spain. Study points were before transplantation and 7 and 30 days after transplantation. Immune parameters included IgG, IgM, IgA and complement factors C3 and C4, and titers of specific antibody to pneumococcal polysaccharide antigens (anti-PPS) and to cytomegalovirus (CMV). To evaluate potential immunologic mechanisms leading to IgG hypogammaglobulinemia, before heart transplantation we assessed serum B-cell activating factor (BAFF) levels using enzyme-linked immunoassay. The clinical follow-up period lasted 6 months. Clinical outcome was need for intravenous anti-microbials for therapy of infection.During follow-up, 53 patients (31.2%) developed at least 1 severe infection. We confirmed that IgG hypogammaglobulinemia at Day 7 (defined as IgG <600 mg/dl) is a risk factor for infection in general, bacterial infections in particular, and CMV disease. At Day 7 after transplantation, the combination of IgG <600 mg/dl + C3 <80 mg/dl was more strongly associated with the outcome (adjusted odds ratio 7.40; 95% confidence interval 1.48 to 37.03; p = 0.014). We found that quantification of anti-CMV antibody titers and lower anti-PPS antibody concentrations were independent predictors of CMV disease and bacterial infections, respectively. Higher pre-transplant BAFF levels were a risk factor of acute cellular rejection.Early immunologic monitoring of humoral immunity profiles proved useful for the identification of heart recipients who are at risk of severe infection.

Cytomegalovirus infection in heart transplantation: A single center experience.

Cytomegalovirus (CMV) infection remains a major complication after heart transplantation with varying prophylaxis strategies employed. We sought to determine the impact of valganciclovir (VGC) duration on the epidemiology of CMV infections after heart transplantation. We performed a prospective cohort study of CMV donor (D) or recipient (R) seropositive heart transplant recipients from 2005 to 2012 who completed VGC prophylaxis, ranging from 3 to 12months according to serostatus and induction immunosuppression. Univariate and multivariate logistic regression was performed. Among 159 heart transplant recipients during the study period, 130 (82%) were eligible for VGC prophylaxis. CMV D/R serostatus was as follows: 24% D+/R-, 30% D+/R+, and 29% D-/R+. 65% and 21% received basiliximab and thymoglobulin induction, respectively, followed by maintenance tacrolimus, mycophenolate mofetil, and prednisone. Twenty-one (16%) recipients suffered CMV infection. There was no association with comorbidities including diabetes mellitus, chronic kidney disease, or mechanical assist devices, nor were there associations with rejection, treatments of rejection, or mortality. When VGC prophylaxis duration was stratified by ≤6 vs ≥12months, time from heart transplantation to CMV infection was delayed (median 247 vs 452days, P=.002) but there was no difference in days from VGC discontinuation to onset of CMV infection (median 72 vs 83days, P=.31). CMV infection occurred most frequently within 6-16weeks of VGC cessation, and 95% of infections occurred during the 6months post-prophylaxis period. Relative to ≤6months, ≥12months of VGC did not reduce incidence of CMV infection and only delayed time to onset. 95% of CMV infection occurs within 6months after cessation of VGC.

Evaluation of humoral immunity profiles to identify heart recipients at risk for development of severe infections: A multicenter prospective study

New biomarkers are necessary to improve detection of the risk of infection in heart transplantation. We performed a multicenter study to evaluate humoral immunity profiles that could better enable us to identify heart recipients at risk of severe infections. We prospectively analyzed 170 adult heart recipients at 8 centers in Spain. Study points were before transplantation and 7 and 30 days after transplantation. Immune parameters included IgG, IgM, IgA and complement factors C3 and C4, and titers of specific antibody to pneumococcal polysaccharide antigens (anti-PPS) and to cytomegalovirus (CMV). To evaluate potential immunologic mechanisms leading to IgG hypogammaglobulinemia, before heart transplantation we assessed serum B-cell activating factor (BAFF) levels using enzyme-linked immunoassay. The clinical follow-up period lasted 6 months. Clinical outcome was need for intravenous anti-microbials for therapy of infection. During follow-up, 53 patients (31.2%) developed at least 1 severe infection. We confirmed that IgG hypogammaglobulinemia at Day 7 (defined as IgG <600 mg/dl) is a risk factor for infection in general, bacterial infections in particular, and CMV disease. At Day 7 after transplantation, the combination of IgG <600 mg/dl + C3 <80 mg/dl was more strongly associated with the outcome (adjusted odds ratio 7.40; 95% confidence interval 1.48 to 37.03; p = 0.014). We found that quantification of anti-CMV antibody titers and lower anti-PPS antibody concentrations were independent predictors of CMV disease and bacterial infections, respectively. Higher pre-transplant BAFF levels were a risk factor of acute cellular rejection. Early immunologic monitoring of humoral immunity profiles proved useful for the identification of heart recipients who are at risk of severe infection.

(774) - CD38+DR+ Expression on Peripheral Monocytes and TLR2 Expression on Plasmocytoid Dendritic Cells May Be Early Markers for Severe Infection in Heart Transplantation

(774) - CD38+DR+ Expression on Peripheral Monocytes and TLR2 Expression on Plasmocytoid Dendritic Cells May Be Early Markers for Severe Infection in Heart Transplantation

(18) - Does the Calcineurin Inhibitor Have Influence on Cytomegalovirus Infection in Heart Transplantation?

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in heart transplant (HTx). Our aim was to analyze the rate of CMV infection in HTx patients receiving treatment with cyclosporine (CsA) or tacrolimus (Tac).

Does the calcineurin inhibitor have influence on cytomegalovirus infection in heart transplantation?

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in heart transplant (HTx). Our aim was to analyze the rate of CMV infection in HTx patients receiving treatment with cyclosporine (CsA) or tacrolimus (Tac). Ninety-five patients were randomized to receive either CsA (53.7%) or Tac (46.3%). We performed prophylaxis with valganciclovir in patients with the highest risk of CMV infection. We considered CMV infection as an increased viral load or the presence of CMV in histological samples. We analyzed baseline characteristics, CMV infection, and other complications. Event-free rates were calculated using the Kaplan-Meier method. There were no significant differences in baseline characteristics between both groups. CMV infection was detected in 31.6% of patients (in 66.7% due to asymptomatic replication). The group treated with Tac had a lower rate of CMV infection (15.9% vs. 45.1%, p=0.002) and longer CMV infection-free survival time (1440 vs. 899d, p=0.001). No differences were observed in the complications analyzed in both groups. The independent risk factors for infection identified in the multivariate analysis were treatment with CsA and bacterial infections. This was the first study to demonstrate a lower rate of CMV infection in patients treated with Tac vs. those treated with CsA after HTx.

66 Donor-Derived Infections in Heart Transplantation

66 Donor-Derived Infections in Heart Transplantation

Sustained virologic response with ribavirin in chronic hepatitis E virus infection in heart transplantation

Hepatitis E virus (HEV) is an emerging problem amongst transplant recipients. We report a patient with chronic HEV hepatitis after a heart transplant. The patient received a 3-month course of oral ribavirin (17 mg/kg/day). HEV RNA became undetectable in the serum after 1 month of treatment and remained undetectable in serum and stool samples until the last follow-up, 2 months after completion of ribavirin therapy. The values of liver function indicators returned to normal reference ranges. The main ribavirin-induced side effect was a significant but well-tolerated anemia. We confirmed that ribavirin may induce a sustained virologic response (4 months after ribavirin cessation) in heart transplant patients with chronic HEV infection. Liver cytolysis is rather common in patients after heart transplantation. Rapid evolution to liver fibrosis lesions and available anti-viral therapy highlight the need to look for HEV infection in heart transplant recipients with unexplained hepatitis.

Surgical wound complications after heart transplantation

Surgical wound complications are more frequent in patients undergoing heart transplantation than in other heart surgery patients. This is probably attributed to the presence of additional risk factors in these patients, such as immunosuppression, mechanical support through assist devices and generally poor health. Analyses of wound infections in heart transplantation are based on smaller patient population than those for general heart surgery, and the reported incidences vary largely. The identification of specific risk factors in heart transplant recipients to date is mainly based on retrospective case-control studies in small patient cohorts, the results are controversial, and the comparability of data is limited because of the lack of application of consistent definitions. The impact of immunosuppression and especially immunosuppression with mammalian target of rapamycin (mTOR) inhibitors on the development of surgical wound complications has been widely discussed following reports of increased occurrence with sirolimus. However, nonheart-transplant specific risk factors should also be considered to develop risk profiles and treatment algorithms for individual patients. Data on surgical wound complications in general heart surgery patients and in heart transplant recipients are compared, the impact of modern immunosuppression reviewed, and areas for further investigation discussed.

Incisional surgical infection in heart transplantation

Incisional surgical site infections (ISSIs) are common bacterial infections in heart transplantation (HT). The purpose of this study was to determine the incidence, etiology, timing, and risk factors for ISSIs. A prospective study was performed, which included all heart transplants carried out in the participating hospitals (pertaining to the Spanish National Hospital Network RESITRA) between August 2003 and February 2005. A population of 292 consecutive patients was included (84.9% males). The definition of ISSI used in the study was based on the Centers for Disease Control criteria. Seventeen episodes of ISSIs were recorded in 14 patients (4.8%; confidence interval [CI] 95% 2.7-7.7%). The median time from transplant to ISSI was 14 days (range 3-75). Two patients (14%) died; fatality was related to ISSI (mediastinitis) in 1 patient (7%). Coagulase-negative staphylococci (7 cases), methicillin-resistant Staphylococcus aureus (3 cases), Proteus mirabilis, extended-spectrum beta-lactamase-producing Escherichia coli, Candida albicans, and Candida glabrata, 1 case each, were the isolated pathogens. The duration of extracorporeal circulation was longer in patients with ISSI, although the difference did not reach statistical significance. Antibiotic prophylaxis with ciprofloxacin alone (odds ratio, 15.8; 95% CI, 1.2-216.9) was independently associated with the development of ISSI. ISSIs in HT are frequently caused by resistant bacteria and Candida, but are associated with good prognosis.

Variations in the Frequency and Type of Infections in Heart Transplantation According to the Immunosuppression Regimen

Objective To evaluate the frequency of infection according to the immunosuppressive regimens used in our center. Materials and methods From 259 consecutive heart transplants we excluded pediatric cases, retransplants, combined transplants (lung and kidney) and immunosuppressive regimens with fewer than 10 cases. The six groups analyzed were: (1) OKT3 (7 days) + cyclosporine (CsA) + mycophenolate mofetil (MMF) + steroids (S); (2) OKT3 (7 days) + CsA + azathioprine (AZA) + S; (3) OKT3 (10 days) + CsA + MMF + S; (4) OKT3 (10 days) + CsA + AZA + S; (5) interleukin-2 (IL-2) antagonists + CsA + MMF + S; (6) IL-2 antagonists + tacrolimus + MMF + S. Infection was considered significant when it causal hospital admission or prolonged hospitalization. Results With a total mean follow-up of 54 ± 43 months, the total percentage of infection-free patients at the end of follow-up was 45.5%. Infection-free survival was lower among patients administered induction with OKT3 antibodies for 10 days, combined with cyclosporine, either with MMF (10%, group 3) or with azathioprine (27%, group 4), compared to those given IL-2 antagonists (particularly in combination with tacrolimus and MMF—69.2%, group 6). Conclusions The results of this study showed that infection was frequent in heart transplantation. Furthermore, induction therapy with OKT3 monoclonal antibodies was associated with an important number of infections (particularly viral infections). Comparison of the treatment groups showed that the regimen associated with fever infections included an IL-2 receptor antagonist with tacrolimus, MMF, and S.

Successful Treatment of Hepatitis B Virus Infection With Lamivudine After Heart Transplantation

Patients with hepatitis B virus (HBV) infection have a higher morbidity and mortality after heart transplantation (HT). HBV infection is endemic in Taiwan. We studied the effect of lamivudine treatment of HBV infection after HT. From July 1987 to July 2005, 252 patients underwent HT. All recipients and donors underwent routine screening of hepatitis B surface antigen (HBsAg), hepatitis B e antigen, antibody to hepatitis B surface antigen, antibody to hepatitis B core antigen, antibody to hepatitis B e antigen, and an alanine aminotransferase (ALT) level before HT. When ALT was two times greater than the upper limit of normal or serum bilirubin was higher than 3 mg/dL in HBsAg-positive patients, HBV-DNA were checked by a branched DNA assay or polymerase chain reaction. When HVB-DNA was greater than 100,000 copies/mL, lamivudine (100 mg per day) was prescribed indefinitely. There were 14 patients under lamivudine treatment after HT, among whom, none suffered severe adverse reactions from lamivudine. Four patients died: one due to end-stage cirrhosis while awaiting liver transplantation at 14 months after HT. Two died of sudden death at 54 months and 138 months after HT. Another died of diffuse B cell lymphoma at 62 months after HT. All the survivors have normal ALT and undetectable HBV-DNA after lamivudine treatment. But the YMDD mutant was detected in two patients. With successful treatment of HBV infection in HT, it is not necessary to exclude HBV infection patients from HT.

IgG monitoring to identify the risk for development of infection in heart transplant recipients

Infectious complication represents a significant source of morbidity and mortality in heart transplant recipients. To assess humoral immunity markers that can predict the development of infection, 38 consecutive recipients of heart transplants performed at a single center were prospectively studied. Induction therapy included daclizumab. Immunoglobulin (IgG, IgA, IgM) and complement factors (C3, C4, and factor B) were performed by nephelometry in peripheral blood samples obtained before transplantation, and 7 days and 1 month after transplantation. During a mean follow-up of 16.9 months, 13 patients had at least one episode of infection (34.2%). Eight of these were cytomegalovirus (CMV) infections treated with intravenous ganciclovir, 2 were bacterial pneumonia, 1 patient had bacterial septicemia, 1 patient had urinary tract infection, and 1 patient had pulmonary nocardiosis. No significant association was found between infection and age, sex, immunosuppression, CMV serostatus of donor and recipient, or treated rejection episodes. Pre-transplant IgG (below median value=1140 mg/dL; relative risk [RR] 3.69; 95% confidence interval [CI] 1.01-13.54; P=0.04) and post-transplant IgG levels at day 7 (below median value=679 mg/dL; RR 11.21; CI 1.04-89.48; P=0.022) were associated with an increase in the risk for developing infections. Early monitoring of immunoglobulin levels might help to identify the risk for developing infection in heart transplantation.

Role of Immunosuppressive Regimen on the Incidence and Characteristics of Cytomegalovirus Infection in Heart Transplantation: A Single-Center Experience With Preemptive Therapy

Objective This retrospective single-center report sought to evaluate the relation of immunosuppressive regimen with the incidence and characteristics of cytomegalovirus (CMV) infection from 1999 to 2003. Patients and methods Immunosuppression consisted of cyclosporine microemulsion (Neoral), azathioprine (AZA), and prednisolone associated with either thymoglobulin or ATG high-dosage induction from 1999 to 2000 (AZA, 64 patients [AZA-Thymo = 38 patients and AZA-ATG 26 patients]), or cyclosporine microemulsion (Neoral), mycophenolate mofetil (MMF), and prednisolone with low-dose thymoglobulin induction from 2001 onward (n = 52 patients). Ganciclovir preemptive therapy was guided by pp65 antigenemia monitoring without CMV prophylaxis. Results The study groups were homogeneous with respect to major perioperative risk factors. Comparing the two AZA subgroups no difference emerged as to percentage of pp65 antigenemia-positive, preemptively treated patients reflecting CMV disease incidence and relapses. AZA-Thymo patient showed significantly shorter time to first positive pp65-antigenemia and higher viral load (AZA-Thymo vs AZA-ATG, P = .004 and P = .009). The two subgroups did not differ with regard to incidence of rejection, superinfection, and graft coronary disease. By shifting from AZA to MMF no difference emerged as to incidence and characteristics of CMV infections, but there was a significant reduction in acute rejection and superinfection (AZA vs MMF P = .001 and P = .008). Conclusions The distinct immunological properties of thymoglobulin versus ATG significantly altered the pattern of CMV expression. MMF with reduced-dose induction did not engender a higher CMV morbidity.

Everolimus is associated with a reduced incidence of CMV infection in heart transplantation

Everolimus is a novel proliferation inhibitor under development for the prevention of rejection in organ transplantation.Purpose: This abstract reports on the 12-month incidence of cytomegalovirus (CMV) infection in the phase 3 heart transplantation study.Methods: Patients (N=634) were randomized to either everolimus 1.5 mg/day (N=209), everolimus 3 mg/day (N=211) or AZA 1–3 mg/kg/day (N=214), with a regimen of cyclosporine (CsA,Neoral), corticosteroids and statins. Laboratory evidence of CMV was determined by antigenemia or PCR. The CMV infection was defined as CMV syndrome (fever for at least 2 days, neutropenia, leukopenia and viral syndrome); or CMV disease (systemic disease with organ involvement); or only laboratory evidence of CMV. CMV prophylaxis was administered in 75% of the patients.Results: Donor/Recipient (D/R) CMV serostatus was evenly distributed across all groups with the high risk group (D+/R-) incidence being 17.2%, 22.7% and 17.3%. Mean duration of CMV prophylaxis was 141, 126 and 110 days in everolimus 1.5 mg, 3 mg and AZA groups respectively (p=ns). The overall incidence of CMV infection was 7.7%, 7.6% and 21.5 % in the everolimus 1.5 mg, 3 mg and AZA groups respectively (p=0.0001). The incidence of CMV syndrome was 1.9% (4 cases), 3.3% (7) and 4.6% (10), and CMV disease was 1.9% (4 cases), 2.3% (5) and 6.5% (14) in everolimus 1.5 mg, 3 mg and AZA groups respectively (p=ns).Conclusions: The incidence of CMV infection was lower in the everolimus groups compared to AZA treated patients and CMV disease was numerically higher in the AZA group. This finding may be of particular significance given the potential role of CMV infection in the development of chronic rejection.