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.

scholarly journals 572. Antiviral Toxicities Among Pediatric Solid Organ Transplant Recipients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S351-S351
Author(s):  
Kevin J Downes ◽  
Anna Sharova ◽  
Marina Mitrou ◽  
Molly Hayes ◽  
Despoina Galetaki ◽  
...  
Keyword(s):  
Medication Management ◽  
Organ Transplant ◽  
Kidney Injury ◽  
Solid Organ Transplant ◽  
Incidence Rates ◽  
First Year ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cmv Disease

Abstract Background Ganciclovir (GCV) and valganciclovir (VGCV) are used for prophylaxis (PPX) and treatment for CMV in pediatric solid organ transplant (SOT) recipients, but the frequency and impact of toxicities from these medications are not well described. Methods Retrospective cohort study of children undergoing SOT at Children’s Hospital of Philadelphia from Jan 2012 - Jun 2018. EMR were reviewed to identify laboratory-based toxicities between 15 days and 1 year post-transplant; medication management within 14 days of toxicity onset was recorded. Toxicities were defined as GCV or VGCV-associated if a patient was on the antiviral at toxicity onset. We defined acute kidney injury (AKI) as ≥50% change in creatinine (Cr) from 30 days prior, leukopenia as WBC < 3500/µL, neutropenia as ANC < 1000/µL, and thrombocytopenia as < 100K/µL. Incidence rates of toxicities on PPX and treatment were compared to rates during no antiviral using univariate Poisson regression. Results 285 children received 299 SOTs: 108 liver, 91 kidney, 69 heart, 31 lung. Nearly half (46%) of toxicities during the first year after transplant occurred while on GCV or VGCV PPX or treatment, but their use accounted for only 23% of all follow-up time. Receipt of VGCV and GCV PPX and treatment were associated with significantly higher incidence rates of toxicities compared to no antiviral (Fig 1). Of 259 GCV or VGCV-associated toxicities, 44% (n=113) were leukopenia, 26% (66) neutropenia, 26% (66) AKI, and 6% (15) thrombocytopenia (Table 1). Most recipients of VGCV PPX (64%) sustained at least one toxicity while on PPX. AKI during VGCV PPX led to stopping/dose-adjusting of VGCV in 43% and of immunosuppression in 57% of cases. Neutropenia during VGCV PPX resulted in stopping/dose-adjusting of VGCV in 63%, of immunosuppression in 36%, and of TMPX/SMX PPX in 36% of cases. During VGCV PPX, 81% of AKI was stage II/III (≥100% change in Cr) and 65% of neutropenia was severe (< 500/µL); 11% of both AKI (n=6) and neutropenia (n=7) during VGCV PPX resulted in hospitalization. Figure 1. Incidence Rates of Toxicities from Day 15 through 1 Year After Transplant Table 1. Antiviral Use and Toxicity 2 Weeks to 1 Year After Transplant Conclusion GCV and VGCV use was associated with significant renal and hematological toxicities in pediatric SOT recipients. While VGCV and GCV are effective at preventing CMV disease in pediatric SOT, clinicians should consider risk of toxicity when evaluating CMV prevention strategies. Disclosures Kevin J. Downes, MD, Merck, Inc. (Grant/Research Support)

scholarly journals 2646. Incidence of Myelosuppression Related to Valganciclovir Prophylaxis in Solid-Organ Transplant Recipients at High Risk of CMV Disease

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S925-S926
Author(s):  
Sara Belga ◽  
Cristina Hernandez ◽  
Dima Kabbani ◽  
Carlos Cervera
Keyword(s):  
Complete Blood Count ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
First Year ◽  
Solid Organ ◽  
Transplant Patients ◽  
Increased Risk ◽  
Cmv Disease ◽  
The Impact

Abstract Background Valganciclovir (VGCV) prophylaxis in solid-organ transplant patients (SOT) is limited by myelotoxicity. We aimed to analyze the impact of VGCV prophylaxis on myelotoxicity and risk factors for its occurrence. Methods Retrospective single-center cohort study of adult CMV-seronegative recipients transplanted between July 2005 and November 2017. CMV D+/R− recipients received 3 to 6 months of VGCV prophylaxis whereas CMV D-/R- received no VGCV. Definitions: leukopenia < 3.5 × 109/L, significant neutropenia < 1.0 × 109/L and significant thrombocytopenia < 50 × 109/L. Results A total of 363 SOT recipients were included, 169 (47%) CMV D+/R− and 194 (53%) CMV D−/R−, with a mean age of 49.5 years and 275 (76%) males; types of organ transplant: 133 (37%) liver, 181 (50%) kidney, 37 (10%) simultaneous kidney-pancreas and 12 (3%) other. Although there was no difference in the incidence of significant neutropenia or thrombocytopenia per transplant type, leukopenia in the first year was more common in liver transplant patients (P < 0.001). New onset leukopenia post-SOT, significant neutropenia (Figure 1) and significant thrombocytopenia in the first year were more common in patients receiving VGCV: 116 D+/R− (69%) vs. 52 D−/R− (31%), P < 0.001; 86 (91%) vs. 9 (9%), P < 0.001; 8 (80%) vs. 2 (20%), P = 0.050; respectively. G-CSF was used more frequently in patients receiving prophylaxis (60% CMV D+/R− vs. 10% CMV D−/R−, P < 0.001). Significant neutropenia had no impact on long-term mortality adjusted by age and transplant type (HR 1.1, 95% CI 0.6–2.1, P = 0.709). Significant neutropenia led to decrease immunosuppression in 90% of patients (vs. 46%, P < 0.001) and was associated with increased risk of rejection (HR 8.5, P < 0.001). In multivariate analysis for significant neutropenia in the first year, VGCV prophylaxis was the only predictor of this outcome after adjusting for confounders (HR 15.1, 95% CI 7.5–30.1, P < 0.001). Conclusion VGCV prophylaxis increased the risk of significant neutropenia by 15-fold post-SOT. No other clinical variables were useful to predict this complication. Therefore, complete blood count monitoring is still needed for all SOT recipients receiving VGCV prophylaxis. Disclosures All authors: No reported disclosures.

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 &lt; 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

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.

scholarly journals Does Post-Transplant Cytomegalovirus Increase the Risk of Invasive Aspergillosis in Solid Organ Transplant Recipients? A Systematic Review and Meta-Analysis

2021 ◽  
Vol 7 (5) ◽  
pp. 327
Author(s):  
Nipat Chuleerarux ◽  
Achitpol Thongkam ◽  
Kasama Manothummetha ◽  
Saman Nematollahi ◽  
Veronica Dioverti-Prono ◽  
...  
Keyword(s):  
Systematic Review ◽  
Invasive Aspergillosis ◽  
Meta Analysis ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Effect Estimate ◽  
Solid Organ ◽  
Post Transplant ◽  
Cmv Disease ◽  
The Impact

Background: Cytomegalovirus (CMV) and invasive aspergillosis (IA) cause high morbidity and mortality in solid organ transplant (SOT) recipients. There are conflicting data with respect to the impact of CMV on IA development in SOT recipients. Methods: A literature search was conducted from existence through to 2 April 2021 using MEDLINE, Embase, and ISI Web of Science databases. This review contained observational studies including cross-sectional, prospective cohort, retrospective cohort, and case-control studies that reported SOT recipients with post-transplant CMV (exposure) and without post-transplant CMV (non-exposure) who developed or did not develop subsequent IA. A random-effects model was used to calculate the pooled effect estimate. Results: A total of 16 studies were included for systematic review and meta-analysis. There were 5437 SOT patients included in the study, with 449 SOT recipients developing post-transplant IA. Post-transplant CMV significantly increased the risk of subsequent IA with pORs of 3.31 (2.34, 4.69), I2 = 30%. Subgroup analyses showed that CMV increased the risk of IA development regardless of the study period (before and after 2003), types of organ transplantation (intra-thoracic and intra-abdominal transplantation), and timing after transplant (early vs. late IA development). Further analyses by CMV definitions showed CMV disease/syndrome increased the risk of IA development, but asymptomatic CMV viremia/infection did not increase the risk of IA. Conclusions: Post-transplant CMV, particularly CMV disease/syndrome, significantly increased the risks of IA, which highlights the importance of CMV prevention strategies in SOT recipients. Further studies are needed to understand the impact of programmatic fungal surveillance or antifungal prophylaxis to prevent this fungal-after-viral phenomenon.

scholarly journals Discordance of SHEA/IDSA Clostridium difficile Disease Severity Scale in Solid Organ Transplant Patients

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S383-S383 ◽  
Author(s):  
Tiffany Lee ◽  
Christopher McCoy ◽  
Carolyn D Alonso ◽  
Graham M Snyder ◽  
Christin Rogers ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Research Support ◽  
Transplant Patients ◽  
Cell Counts ◽  
Immunocompromised Status ◽  
White Blood Cell Counts ◽  
Healthcare Epidemiology

Abstract Background Solid organ transplant (SOT) patients are at high risk for Clostridium difficile infections (CDI) due to chronic immunosuppression and a propensity to receive antimicrobials. Management of CDI in SOT patients poses unique challenges as this population has disease-altered clinical and laboratory parameters. The objective of this study was to assess concordance between various CDI severity scales and the Society for Healthcare Epidemiology of America/Infectious Diseases Society of America (SHEA/IDSA) guidelines. Methods This retrospective study included all SOT recipients with a first CDI episode following transplant and time-matched (2:1) to non-SOT patients experiencing first CDI episodes between 2008 and 2016. The primary endpoint was concordance rates of CDI episodes considered mild-moderate or severe/severe-complicated in published CDI scales compared with the SHEA/IDSA guidelines. We also sought to compare the distribution of CDI severity across all scales between SOT and non-SOT patients. Results Overall, 32 SOT patients and 64 non-SOT patients were included. The SOT group had significantly higher leukopenia rates at CDI diagnosis; however, the magnitude of serum creatinine change did not differ between groups. According to the SHEA/IDSA scale, CDI episodes in SOT recipients were categorized as mild-moderate and severe/severe-complicated in 23 (72%) and 9 (28%) patients, respectively. Overall concordance rates among SHEA/IDSA guidelines and other scales ranged from 28% to 72%. Concordance rates were highest for mild-moderate CDI with Belmares and for severe/severe-complicated CDI with ESCMID (Table 1). No scale evenly categorized SOT and non-SOT patients across all severities (Figure 1). Conclusion Severity scales with heavy emphasis on white blood cell counts may not adequately categorize SOT patients. Immunocompromised status may need to be considered on its own when categorizing CDI severity and prescribing therapy. Disclosures C. D. Alonso, Merck: Grant Investigator and Scientific Advisor, Research grant sanofi pasteur: Investigator and Scientific Advisor, Research support GSK: Investigator, Research support; E. B. Hirsch, Merck: Grant Investigator, Grant recipient The Medicines Company: Speaker’s Bureau, Speaker honorarium

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.

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