scholarly journals 1079. The Risk of Cytomegalovirus (CMV) Infection and Recurrence Among Solid Organ Transplant Recipients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S567-S568
Author(s):  
Joanne Reekie ◽  
Mark P Khurana ◽  
Isabelle P Lodding ◽  
Christina Ekenberg ◽  
Finn Gustafsson ◽  
...  
Keyword(s):  
High Risk ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Older Age ◽  
First Year ◽  
Solid Organ ◽  
Cmv Infection ◽  
Factors Associated ◽  
Stopping Treatment ◽  
Cmv Prophylaxis

Abstract Background Solid organ transplant (SOT) recipients are at a high risk of developing cytomegalovirus (CMV) post-transplant (tx) with many experiencing a recurrence shortly after clearing the first episode. We aimed to identify risk factors associated with CMV infection and recurrence. Methods SOT recipients (≥ 18 years) transplanted between 2011-2016 were investigated for factors associated with CMV infection within 1 year from baseline and recurrent CMV within 6 months of stopping CMV treatment for the first infection using cumulative incidence curves and Cox proportional hazards models. Baseline was defined as either tx date or date of stopping CMV prophylaxis for those initiating CMV prophylaxis within 7 days of tx. Individuals with breakthrough CMV while on prophylaxis were excluded (n=29). Figure 1 Risk of CMV infection in 755 SOT recipients in the first year from baseline, stratified by CMV serostatus. Baseline was defined either the date of transplant (n=285) or stopping CMV prophylaxis (n=470). Figure 2 Factors associated with CMV infection in the first year from baseline. Baseline was defined either the date of transplant (n=285) or stopping CMV prophylaxis (n=470). Results We included 755 SOT recipients, 173(23%) developed CMV infection within one year of baseline with CMV disease present at diagnosis in 17% of the cases. The risk of CMV infection was lower in patients with low (aHR 0.19, 95%CI 0.12-0.29) and intermediate (aHR 0.26, 95%CI 0.18-0.36) risk CMV IgG serostatus compared to high risk (Figure1). Liver and lung tx, female sex, older age and year of tx were also associated with an increased risk of CMV infection (Figure 2). Among the 470 (62%) patients who received CMV prophylaxis those who received < 85 days had a higher risk of CMV infection than those receiving ≥ 85 days (aHR 1.80, 95%CI 1.19-2.72). 99 recipients were investigated for recurrent CMV; 40 (40%) experienced relapse within 6 months of stopping treatment for their first infection. The risk of recurrent CMV was significantly lower in those with low (aHR 0.20, 95%CI 0.06-0.74) and intermediate risk serostatus (aHR 0.40, 95%CI 0.19-0.84) (Figure 3). Older age (aHR 1.23 per 5 years older, 95%CI 1.06-1.44) was also significantly associated with recurrent CMV infection (Figure 4). Figure 3 Risk of recurrent CMV infection in the 6 months following clearance and stopping of treatment for the first CMV infection (N=99), stratified by CMV serostatus at the time of transplant Figure 4 Factors associated with recurrent CMV infection within 6 months of stopping treatment for the first CMV infection Conclusion Recurrent CMV infection remains a significant complication among SOT recipients, especially in those with high risk CMV IgG serostatus. These findings highlight the necessity to successfully treat and monitor this subgroup following their first infection. Novel medical interventions and strategies to prevent CMV infection are of particular importance to this high risk group. Disclosures All Authors: No reported disclosures

scholarly journals 1744. CMV Infection and Management Among Pediatric Solid-Organ Transplant Recipients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S639-S639
Author(s):  
Anna Sharova ◽  
Despoina M Galetaki ◽  
Molly Hayes ◽  
Lauren Gianchetti ◽  
Laura A Vella ◽  
...  
Keyword(s):  
Organ Transplant ◽  
Solid Organ Transplant ◽  
First Year ◽  
Invasive Infection ◽  
Solid Organ ◽  
Cmv Infection ◽  
Research Support ◽  
Free Survival ◽  
Medium Risk ◽  
Cmv Disease

Abstract Background Our institution provides universal CMV prophylaxis (PPX) for all high (D+/R-) and medium risk (R+) solid-organ transplant (SOT) recipients. We sought to evaluate this practice by assessing CMV infection and disease within the first year of SOT. Methods Retrospective cohort study of all children undergoing first SOT at Children’s Hospital of Philadelphia from January 2012 to October 2017. We identified recipients with CMV infection (detection of CMV DNA in body fluid/tissue with or without symptoms) and disease (symptomatic or tissue-invasive infection) in the first year after SOT. We calculated the rate of CMV infection and compared CMV-free survival based on SOT type and CMV risk using log-rank tests. Results 244 children received 246 SOTs: 90 liver, 70 kidney, 59 heart, 27 lung. In total, 39 children (16%) had 49 CMV infections in the first year after SOT, including 29% of high (n = 21/72) and 23% of medium risk recipients (n = 16/69). The fraction of each organ type with CMV infection was similar (Figure 1, P = 0.33). Among high and medium risk recipients, all of whom received PPX, the incidence rate of CMV infection in the first year post-SOT was similar: 10.1 vs. 7.8/10,000 days (P = 0.22). There were no differences in CMV-free survival by organ (Figure 2, log-rank P = 0.25) or between high and medium risk recipients (Figure 3, log-rank P = 0.46). In total, 22% (n = 10/45) of CMV infections in high/medium risk patients occurred while on PPX; half were in the setting of reduced PPX dosing or within 2 weeks of SOT. Of the 35 CMV infections post-PPX, the median time to detection of CMV after PPX was 39 days (IQR 28–98). There were 11 cases (6 high, 5 medium risk) of CMV disease: 6 CMV syndrome, 2 hepatitis, 2 pneumonitis, 1 GI disease. Valganciclovir was more often used for treatment of asymptomatic infections than for CMV disease (79% vs. 33%, P = 0.03). All-cause mortality in the first year post-SOT was similar among those with and without CMV infections (7.7 vs. 6.3%, P = 0.76) and among those with and without CMV disease (9.1 vs. 5.2%, P = 0.57). Conclusion CMV infection was common in high and medium risk SOT recipients in the first year following SOT, and most infections occurred off of PPX. Our data suggest that the highest risk period for CMV infection is in the first months after PPX, and that monitoring may be most useful after PPX has been stopped or when PPX doses are reduced. Disclosures Kevin J. Downes, MD, Merck: Grant/Research Support, Research Grant; Pfizer: Grant/Research Support.

Cytomegalovirus in Solid Organ Transplant Recipients: Clinical Updates, Challenges and Future Directions

2020 ◽  
Vol 26 (28) ◽  
pp. 3497-3506
Author(s):  
Raymund R. Razonable
Keyword(s):  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cmv Infection ◽  
Future Directions ◽  
Prevention And Treatment ◽  
Solid Organ Transplant Recipients

Cytomegalovirus is the classic opportunistic infection after solid organ transplantation. This review will discuss updates and future directions in the diagnosis, prevention and treatment of CMV infection in solid organ transplant recipients. Antiviral prophylaxis and pre-emptive therapy are the mainstays of CMV prevention, but they should not be mutually exclusive and each strategy should be considered depending on a specific situation. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is emphasized as a major factor that should pave the way for an individualized approach to prevention. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management, and strategies for managing drug-resistant CMV infection are enumerated. There is increasing use of CMV-specific cell-mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, and their potential role in optimizing CMV prevention and treatment efforts is discussed.

scholarly journals Hepatitis E Virus Quasispecies and the Outcome of Acute Hepatitis E in Solid-Organ Transplant Patients

2012 ◽  
Vol 86 (18) ◽  
pp. 10006-10014 ◽  
Author(s):  
Sebastien Lhomme ◽  
Florence Abravanel ◽  
Martine Dubois ◽  
Karine Sandres-Saune ◽  
Lionel Rostaing ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Acute Hepatitis ◽  
Hepatitis E Virus ◽  
Organ Transplant ◽  
Hepatitis E ◽  
Solid Organ Transplant ◽  
First Year ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Serum Concentrations

Hepatitis E virus (HEV) infections are responsible for chronic hepatitis in immunocompromised patients, and this can evolve to cirrhosis. Like all RNA viruses, HEV exists as a mixture of heterogeneous viruses defining quasispecies. The relationship between the genetic heterogeneity described as a quasispecies, cytokine secretion, and the outcome of acute hepatitis in immunocompromised patients remains to be elucidated. We cloned and sequenced the region encoding the M and P capsid domains of HEV from eight solid-organ transplant (SOT) patients with acute HEV infection who subsequently cleared the virus and from eight SOT patients whose infection became chronic. We analyzed the cytokines and chemokines in the sera of these SOT patients by multianalyte profiling. The nucleotide sequence entropy and genetic distances were greater in patients whose infections became chronic. A lowerKa/Ksratio was associated with the persistence of HEV. The patients who developed chronic infection had lower serum concentrations of interleukin-1 (IL-1) receptor antagonist and soluble IL-2 receptor. Increased concentrations of the chemokines implicated in leukocyte recruitment to the liver were associated with persistent infection. Those patients with chronic HEV infection and progressing liver fibrosis had less quasispecies diversification during the first year than patients without liver fibrosis progression. Great quasispecies heterogeneity, a weak inflammatory response, and high serum concentrations of the chemokines involved in leukocyte recruitment to the liver in the acute phase were associated with persistent HEV infection. Slow quasispecies diversification during the first year was associated with rapidly developing liver fibrosis.

Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Solid-organ Transplant Recipients on Continuous Veno-venous Hemodialysis

2020 ◽  
Author(s):  
Andrew S Jarrell ◽  
Jessica R Crow ◽  
Sara E Strout ◽  
Rachel M Kruer ◽  
Lindsey P Toman ◽  
...  
Keyword(s):  
Organ Transplant ◽  
Population Based ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Open Label ◽  
Intravenous Ganciclovir ◽  
Trough Concentrations ◽  
Average Body Mass ◽  
Bilateral Lung ◽  
Cmv Prophylaxis

Abstract Background Optimal valganciclovir dosing for cytomegalovirus (CMV) prophylaxis in solid-organ transplant (SOT) patients on continuous veno-venous hemodialysis (CVVHD) is not known. Ganciclovir trough concentrations ≥0.60 μg/mL have been suggested for CMV prophylaxis. This study was conducted to determine if valganciclovir 450 mg enterally every 24 hours achieves ganciclovir trough concentrations ≥0.60 μg/mL in patients on CVVHD. Methods This single-center, prospective, open-label, pharmacokinetic study included adult SOT patients admitted to an intensive care unit from March 2018 to June 2019 on CVVHD. All patients were receiving valganciclovir 450 mg enterally every 24 hours for CMV prophylaxis prior to enrollment. Each patient had a peak and trough sample drawn at steady state. Results Ten SOT patients were included in the study (6 liver, 1 simultaneous liver-kidney, 2 bilateral lung, 1 heart). The mean ± SD age was 51.8 ± 14.0 years, and average body mass index was 27 ± 6.9 kg/m2. Ganciclovir trough concentrations ranged from 0.31 to 3.16 μg/mL, and 80% of participants have trough concentrations ≥0.60 μg/mL. No patients had documented neutropenia while on valganciclovir and CVVHD; 60% of patients had significant thrombocytopenia. Conclusions Valganciclovir 450 mg enterally every 24 hours achieved ganciclovir trough concentrations ≥0.60 μg/mL in most patients on CVVHD, similar to those reported with intravenous ganciclovir for prophylaxis in this population. Based on these data, valganciclovir may require dosing every 24 hours to achieve concentrations equivalent to ganciclovir. Neutropenia did not occur in the study period. Thrombocytopenia was common and likely multifactorial.

scholarly journals The Impact of Culturing the Organ Preservation Fluid on Solid Organ Transplantation: A Prospective Multicenter Cohort Study

2019 ◽  
Vol 6 (6) ◽  
Author(s):  
I Oriol ◽  
N Sabe ◽  
J Càmara ◽  
D Berbel ◽  
M A Ballesteros ◽  
...  
Keyword(s):  
High Risk ◽  
Antibiotic Therapy ◽  
Graft Rejection ◽  
Graft Loss ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Preemptive Therapy ◽  
Solid Organ ◽  
Risk Culture ◽  
Culture Positive

Abstract Background We analyzed the prevalence, etiology, and risk factors of culture-positive preservation fluid and their impact on the management of solid organ transplant recipients. Methods From July 2015 to March 2017, 622 episodes of adult solid organ transplants at 7 university hospitals in Spain were prospectively included in the study. Results The prevalence of culture-positive preservation fluid was 62.5% (389/622). Nevertheless, in only 25.2% (98/389) of the cases were the isolates considered “high risk” for pathogenicity. After applying a multivariate regression analysis, advanced donor age was the main associated factor for having culture-positive preservation fluid for high-risk microorganisms. Preemptive antibiotic therapy was given to 19.8% (77/389) of the cases. The incidence rate of preservation fluid–related infection was 1.3% (5 recipients); none of these patients had received preemptive therapy. Solid organ transplant (SOT) recipients with high-risk culture-positive preservation fluid receiving preemptive antibiotic therapy presented both a lower cumulative incidence of infection and a lower rate of acute rejection and graft loss compared with those who did not have high-risk culture-positive preservation fluid. After adjusting for age, sex, type of transplant, and prior graft rejection, preemptive antibiotic therapy remained a significant protective factor for 90-day infection. Conclusions The routine culture of preservation fluid may be considered a tool that provides information about the contamination of the transplanted organ. Preemptive therapy for SOT recipients with high-risk culture-positive preservation fluid may be useful to avoid preservation fluid–related infections and improve the outcomes of infection, graft loss, and graft rejection in transplant patients.

scholarly journals Hepatitis E Virus Infection Among Solid Organ Transplant Recipients at a North American Transplant Center

2016 ◽  
Vol 3 (1) ◽  
Author(s):  
Paul K. Sue ◽  
Nora Pisanic ◽  
Christopher D. Heaney ◽  
Michael Forman ◽  
Alexandra Valsamakis ◽  
...  
Keyword(s):  
Risk Factors ◽  
North America ◽  
Hepatitis E Virus ◽  
Organ Transplant ◽  
Hepatitis E ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Factors Associated ◽  
Solid Organ Transplant Recipients

Abstract Background.  Autochthonous hepatitis E virus (HEV) infection has been reported in over 200 solid organ transplant (SOT) recipients since 2006, yet little is known about the burden of HEV among SOT recipients in North America. We performed a retrospective, cross-sectional study to investigate the prevalence and risk factors associated with HEV infection among SOT recipients at our institution. Methods.  Children and adults (n = 311) who received allografts between 1988 and 2012 at the Johns Hopkins Hospital were assessed for evidence of HEV infection by testing posttransplantation serum samples for HEV antibody by enzyme immunoassay and HEV RNA by reverse transcription quantitative polymerase chain reaction. Individuals with evidence of posttransplant HEV infection (presence of anti-HEV immunoglobulin [Ig]M antibody, anti-HEV IgG seroconversion, or HEV RNA) were compared with individuals without evidence of infection and assessed for risk factors associated with infection. Results.  Twelve individuals (4%) developed posttransplant HEV infection. Posttransplant HEV infection was associated with an increased risk for graft rejection (odds ratio, 14.2; P = .03). No individuals developed chronic infection. Conclusions.  Solid organ transplant recipients in the United States are at risk for posttransplant HEV infection. Further studies are needed to characterize environmental risk factors and the risk of HEV infection after SOT in North America.

New Strategies for Prevention and Therapy of Cytomegalovirus Infection and Disease in Solid-Organ Transplant Recipients

2000 ◽  
Vol 13 (1) ◽  
pp. 83-121 ◽  
Author(s):  
Irene G. Sia ◽  
Robin Patel
Keyword(s):  
Antiviral Agents ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Cmv Infection ◽  
Human Organ ◽  
Preventative Measures ◽  
Daunting Task ◽  
History Of ◽  
Antiviral Chemotherapy

SUMMARY In the past three decades since the inception of human organ transplantation, cytomegalovirus (CMV) has gained increasing clinical import because it is a common pathogen in the immunocompromised transplant recipient. Patients may suffer from severe manifestations of this infection along with the threat of potential fatality. Additionally, the dynamic evolution of immunosuppressive and antiviral agents has brought forth changes in the natural history of CMV infection and disease. Transplant physicians now face the daunting task of recognizing and managing the changing spectrum of CMV infection and its consequences in the organ recipient. For the microbiology laboratory, the emphasis has been geared toward the development of more sophisticated detection assays, including methods to detect emerging antiviral resistance. The discovery of novel antiviral chemotherapy is an important theme of clinical research. Investigations have also focused on preventative measures for CMV disease in the solid-organ transplant population. In all, while much has been achieved in the overall management of CMV infection, the current understanding of CMV pathogenesis and therapy still leaves much to be learned before success can be claimed.

Cardiac Complications Following Allogeneic Bone Marrow Transplantation: Evaluation of Risk Factors, Outcomes and Enhanced Screening for At Risk Populations.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3070-3070
Author(s):  
Michael Henry ◽  
Rong Guo ◽  
Mala Parthasarathy ◽  
John Lopez ◽  
Patrick Stiff
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
High Risk ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Low Risk ◽  
Solid Organ ◽  
Cardiac Events ◽  
Post Transplant ◽  
Risk Patients

Abstract Abstract 3070 Life-threatening cardiac events following allogeneic bone marrow transplants (BMT) are not uncommon at 5–12.5% of patients. While BMT programs perform screening EKGs and ejection fraction measurements, solid organ transplant centers follow a risk stratification screening algorithm to assess for coronary artery disease (CAD) which includes stress tests and as indicated, angiography in those with 2 or more risk factors. It is currently unknown whether this algorithm should be applied in the BMT setting. Methods: We performed a retrospective review of 296 patients who underwent allogeneic BMT at Loyola University Medical Center 2007–2011, to assess cardiac events using the solid organ transplant advanced screening criteria: age over 60 or over 40 with peripheral vascular disease or diabetes and then divided patients into low risk (one CV risk factor) and high risk groups (greater than one CV risk factor). Risk factors included age, hypertension, diabetes, smoking, family history of CAD, and obesity according to the Framingham risk assessment score for CAD. Cardiac events during the first year post-transplant were recorded including CHF, myocardial infarction (MI), and symptomatic arrhythmias. One hundred day and 1-year Kaplan-Meier survival for high and low risk patients were determined and curves compared by log-rank tests. A multivariate analysis of the various prognostic factors was performed using the Cox regression model. Results: Of the 296 total allografts, 116 patients (39%) fit the solid organ transplant criteria for advanced screening; 62% were male (n = 72) and the mean age was 60.6 (range 40–72). Graft source was evenly distributed between siblings (42%), unrelated (39%) and cord blood (28%). Acute myeloid leukemia was the most common indication for BMT at 40%, followed by MDS (21%), non-Hodgkin lymphoma (16%), and CLL (10%). Of the 116, 21 were considered low risk (1 risk factor), while 95 were high risk (2+ risk factors). Low risk and high risk groups did not differ in disease type (p = 0.43), graft source (p = 0.81), or graft type (p = 0.54). Surprisingly, both high and low risk patients had a similar incidence of cardiac events of 36% and 48%, respectively. This correlated to comparable 100-day and 1 year survival rates. To determine the importance of cardiac complications on outcome and whether there were other risk factors for complications we analyzed those with a complication. Forty-four cardiac events occurred in the first year after transplant in 38 (33%) patients. Cardiac events included arrhythmias (n = 33), new onset CHF (n = 6), and MI (n = 5). Median time to event was 16 days post-transplant. Symptomatic arrhythmias included atrial fibrillation (n = 27, 82%), supraventricular tachycardia (n = 5, 15%) and sustained ventricular tachycardia (n =1, 3%). Median age for patients with cardiac events was 62.7 years, compared to 59.6 for patients who experienced no cardiac events (hazard ratio estimate: 1.076; p = 0.02). As compared to patients with no post-transplant cardiac events, both the 100 day and 1 year survival rates of patients with cardiac events were lower with one year survival of 21% vs. 63% (p < 0.0001). Evaluating risk factors, 3 were significant: donor source with MUD donors the highest hazard (p = 0.04); age, with cardiac events occurring at a rate twice as high in patients greater than age 60 (n = 27, 36.5% vs. n = 6, 19.4%), and with all five cases of myocardial infarction and 5/6 new CHF diagnoses occurring in patients aged 60 or greater; and patients with a history of atrial fibrillation demonstrated a higher probability of developing a cardiac event post-transplant (p = 0.02). Conclusions: In this analysis, we saw a much higher incidence of post-BMT cardiac events (33%) than previously reported, although we focused only on at risk patients using the solid organ screening algorithm (pts > 40 with significant risk factors or all pts > 60). As mortality rates at 100 day and 1 year are higher for patients who suffer a post-BMT cardiac event, and only graft source, age and prior atrial fibrillation marked patients at a very high risk, this data indicates that it is appropriate to investigate prospectively the solid organ transplant algorithm in all allogeneic BMT patients > age 40, with low cardiac risk or any patient > 60 with stress tests and as indicated, cardiac catheterization. Whether this will decrease events and thereby improve survival remains to be determined by prospective studies. Disclosures: No relevant conflicts of interest to declare.

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