scholarly journals Herpes Zoster in Solid Organ Transplantation: Incidence and Risk Factors

2021 ◽  
Vol 12 ◽  
Author(s):  
Marcia M. L. Kho ◽  
Stefan Roest ◽  
Dominique M. Bovée ◽  
Herold J. Metselaar ◽  
Rogier A. S. Hoek ◽  
...  
Keyword(s):  
Risk Factors ◽  
Herpes Zoster ◽  
Multivariable Analysis ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Clinical Signs ◽  
Significant Risk ◽  
Solid Organ ◽  
Disseminated Disease ◽  
Cmv Prophylaxis

BackgroundStudies on herpes zoster (HZ) incidence in solid organ transplant (SOT) recipients report widely varying numbers. We investigated HZ incidence, severity, and risk factors in recipients of four different SOTs, with a follow-up time of 6–14 years.MethodsRecords of 1,033 transplant recipients after first heart (HTx: n = 211), lung (LuTx: n = 121), liver (LiTx: n = 258) and kidney (KTx: n = 443) transplantation between 2000 and 2014 were analyzed for VZV-PCR, clinical signs of HZ, and complications.ResultsHZ was diagnosed in 108 of 1,033 patients (10.5%): 36 HTx, 17 LuTx, 15 LiTx, and 40 KTx recipients. Overall HZ incidence rate after HTx (30.7 cases/1,000 person–years (PY)), LuTx (38.8 cases/1,000 PY), LiTx (22.7 cases/1,000 PY) and KTx (14.5 cases/1,000 PY) was significantly higher than in the general 50–70 year population. Multivariable analysis demonstrated age ≥50 years at transplantation (p = 0.038, RR 1.536), type of organ transplant (overall p = 0.002; LuTx p = 0.393; RR 1.314; LiTx p = 0.011, RR 0.444; KTx p = 0.034, RR 0.575), CMV prophylaxis (p = 0.043, RR 0.631) and type of anti-rejection therapy (overall p = 0.020; methylprednisolone p = 0.008, RR 0.475; r-ATG p = 0.64, RR1.194) as significant risk factors. Complications occurred in 33 of 108 (31%) patients (39% of HTx, 47% of LuTx, 20% of LiTx, 20% of KTx): post-herpetic neuralgia, disseminated disease, and cranial nerve involvement.ConclusionHZ incidence and severity in SOT recipients are most pronounced after heart and lung transplantation, in older patients, and when CMV prophylaxis is lacking.

scholarly journals Incidence and Risk Factors Associated with Fatal Graft Vs Host Disease after Solid Organ Transplantation in United Network of Organ Transplant Database

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4067-4067
Author(s):  
Pavan Tenneti ◽  
Jiaxian He ◽  
Peter Lalli ◽  
Pranav Tenneti ◽  
Michael R. Grunwald ◽  
...  
Keyword(s):  
Risk Factors ◽  
Organ Transplantation ◽  
Cause Of Death ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ ◽  
Cell Transplant ◽  
Abo Incompatibility ◽  
And Gender ◽  
High Level

Abstract INTRODUCTION Graft vs host disease (GVHD) is a rare complication after solid organ transplantation ( ̴ 1-2% with liver and ̴ 5.6% with intestines), but is associated with high mortality (70-80%). In contrast to GVHD following hemopoietic stem cell transplant, bone marrow infiltration by donor T lymphocytes leading to cytopenia ( ̴ 80%) is a common manifestation of GVHD after solid organ transplantation (Murali et. al., 100(12), Transplantation, January 2016). The risk factors associated with GVHD occurring after solid organ transplantation have not been well characterized, but single institution studies have suggested donor/recipient (D/R) HLA mismatch, ABO incompatibility and gender mismatch playing important roles. However, some studies have identified that similarities in HLA type which permit mismatches unrecognized by the recipient as a common mechanism preventing rejection of donor lymphocytes, which then can cause GVHD in the recipient. In order to evaluate potential risk factors, we reviewed the transplant data of patients in whom GVHD was listed as the cause of death from United Network of Organ transplant database (UNOS), the database that contains all US organ transplant data. METHODS From the UNOS database we obtained information of patients that underwent liver or intestinal transplantation between 1987-2020 in the US. The patients for whom GVHD was reported as the cause of death were identified. Baseline D/R and transplant variables were collected. Patient or transplant related characteristics were presented via descriptive statistics. Corresponding P-values were determined using Chi-square test for categorical variables and two-sample t-test for continuous variables. The incidence of mortality caused by GVHD was estimated using the cumulative incidence method, accounting for non-GVHD related death as a competing risk. All statistical tests were two sided, and a P-value < 0.05 was considered significant. RESULTS Of a total of 179,355 patients that underwent liver transplantation, 216 (0.1%) patients had GVHD identified as the primary cause of death (GVHD group). The HLA mismatch information was available in 86,434 patients (48.2%). HLA mismatch was grouped into low level (0-3) and high level (4-6). Low level HLA mismatch was 24.6% in the GVHD group compared to 16.2% in patients that are alive or died of non-GVHD related causes (non-GVHD group). High level mismatch was 75.4% in GVHD group and 83.8% in the non-GVHD group (P=0.013). Other risk factors including gender mismatch (40.3% vs 42.5%, P=0.536), ABO incompatibility between D/R (0.5% vs 1.4%, P=0.42) and use of live donors (1.9% vs 4.3%, p= 0.09) were similar between the two groups. Patients in the GVHD group were older with median age of recipient being 59 years compared to 53 years in the non-GVHD (P<0.001). Graft failure was more common in the GVHD group compared to non-GVHD group (33.8% vs 17.1%, P<0.001). Of a total of 3,153 patients that underwent intestinal transplantation, 20 (0.6%) patients had GVHD identified as the primary cause of death (GVHD group). The HLA mismatch information was available in 2859 patients (90.6%).The high-level HLA mismatch (83.3% vs 84.7%, P=0.749), gender mismatch (40% vs 47.1%, P=0.655) and ABO incompatibility (0% vs 0.2%, P=0.757) between D/R were similar between the GVHD group and non-GVHD group among intestinal transplant patients. Conclusions In patients that undergo hematopoietic stem cell transplant, HLA and gender mismatch between D/R have been recognized as risk factors for GVHD. Based on the largest analysis of solid organ transplant database, traditionally considered GVHD risk factors like HLA and gender mismatch between D/R do not appear to be significantly associated with severe GVHD leading to death. Recipient age and graft failure are significantly associated with GVHD related deaths in liver transplant patients. These findings suggest that other risk factors for severe GVHD leading to death after solid organ transplant than those previously reported in single institution studies should be examined and underscore the need for additional studies. Figure 1 Figure 1. Disclosures Grunwald: Med Learning Group: Other; Agios: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; Janssen: Research Funding; Amgen: Consultancy; Pfizer: Consultancy; PRIME: Other; PER: Other; Karius: Consultancy; Sierra Oncology: Consultancy; Blueprint Medicines: Consultancy; Incyte: Consultancy, Research Funding; AbbVie: Consultancy; Bristol Myers Squibb: Consultancy; Stemline: Consultancy; Gilead: Consultancy; Cardinal Health: Consultancy; Trovagene: Consultancy; MDEdge: Other. Copelan: Amgen: Consultancy.

scholarly journals Coccidioidomycosis After Solid Organ Transplantation: A Population-Based Study

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S75-S76 ◽  
Author(s):  
Ige George ◽  
Carlos Santos
Keyword(s):  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Population Level ◽  
Population Based ◽  
Solid Organ ◽  
Endemic Region ◽  
Billing Data ◽  
Level Data ◽  
Disseminated Disease

Abstract Background Coccidioidomycosis is an invasive fungal infection in solid organ transplantation (SOT) recipients with an incidence of 1.4–6.9% in endemic regions. There are no population-level data describing the incidence and outcomes of coccidioidomycosis in SOT recipients. Methods We assembled a large cohort of adult SOT recipients using ICD-9-CM billing data from the California State Inpatient Databases from 2004 to 2011. Demographics, comorbidities, coccidioidomycosis coded during hospitalization and inpatient death were identified. We used Cox proportional hazard multivariate analyses to identify risk factors for coccidioidomycosis and death. Results 20,602 SOT recipients were identified during the study period (median follow-up time = 1507 days). Eighty-seven patients (0.42%) with coccidioidomycosis were identified of whom 17 (20%) were coded with progressive/disseminated disease. Median time to diagnosis was 164 days (IQR 16–844) from transplantation. Fifty-one of 87 (58%) of these infections were diagnosed within the first year posttransplant and 29/87 (33.3%) were identified within the first month. Twenty-one of 87 (24%) of patients with coccidioidomycosis died compared with 1928/18587 (9.4%) of patients without coccidioidomycosis (P < 0.001). Coccidioidomycosis was independently associated with death (HR, 3.1; 95% CI, 2.0–4.4), after adjusting for age, type of transplantation, transplant failure/rejection, and other comorbidities (Table) (Figure). Conclusion Coccidioidomycosis resulting in hospitalization is rare in an endemic region in the current era of screening and prophylactic antifungal therapy. Preventing infection in solid organ transplant recipients is imperative because overall mortality remains high. Disclosures All authors: No reported disclosures.

Fosfomycin tromethamine for the Treatment of Cystitis in Abdominal Solid Organ Transplant Recipients With Renal Dysfunction

2017 ◽  
Vol 51 (9) ◽  
pp. 751-756 ◽  
Author(s):  
Luiza Kerstenetzky ◽  
Margaret R. Jorgenson ◽  
Jillian L. Descourouez ◽  
Glen Leverson ◽  
Warren E. Rose ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Dysfunction ◽  
Normal Renal Function ◽  
Treatment Success ◽  
Multivariable Analysis ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Significant Difference

Background: Urinary tract infection (UTI) after abdominal solid organ transplantation (SOT) is associated with significant morbidity and mortality. Fosfomycin tromethamine (FOS), a uroselective antibiotic, is FDA approved for uncomplicated UTIs in women and is used off-label for complicated UTIs and prostatitis in men. Literature supporting the use of FOS in the SOT population is limited, and efficacy is questioned in the setting of renal dysfunction. Objective: To evaluate the success of FOS for the treatment of cystitis in SOT patients with renal dysfunction. Methods: This was a single-center, retrospective study using medical records. SOT recipients receiving at least 1 dose of FOS for treatment of cystitis between January 1, 2009, and April 30, 2015, were included. Treatment outcomes were analyzed with respect to renal function. Results: A total of 76 courses of FOS were identified in 64 patients. The renal dysfunction arm (creatinine clearance [CrCl] < 40 mL/min) included 33 patients with 39 FOS courses; the normal renal function arm (CrCl ≥ 40 mL/min) included 31 patients with 37 FOS courses. Mean CrCl was 23.3 ± 9.7 mL/min for the renal-dysfunction group and 65 ± 29.3 mL/min for the normal renal function group ( P < 0.01). No significant difference in treatment success was noted between CrCl <40 mL/min and CrCl ≥40 mL/min (31 [80%] vs 34 [92%], P = 0.12) in a unilateral analysis. After adjusting for confounders in a multivariable analysis, there was no difference in the risk of failure between CrCl <40 mL/min and CrCl ≥40 mL/min groups ( P = 0.70). Conclusion: FOS appears to be successful for the treatment of cystitis in SOT recipients in the setting of renal dysfunction.

scholarly journals A Combined HLA Molecular Mismatch and Expression Analysis for Evaluating HLA-DPB1 de novo Donor-Specific Antibody Risk in Pediatric Solid Organ Transplantation: Implications for Solid Organ & Hematopoietic Stem Cell Transplantation

2020 ◽  
Author(s):  
Mengkai Shieh ◽  
Tristan J. Hayeck ◽  
Anh Dinh ◽  
Jamie L. Duke ◽  
Nilesh Chitnis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Organ Transplantation ◽  
Cell Transplantation ◽  
Specific Antibody ◽  
De Novo ◽  
Strong Association ◽  
Multivariable Analysis ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Hematopoietic Stem

ABSTRACTBackgroundHLA molecular mismatch (MM) has been shown to be a risk factor for de novo donor-specific antibody (dnDSA) development in solid organ transplantation (SOT). HLA expression differences have also been associated with adverse outcomes in hematopoietic cell transplantation. We sought to study both MM and expression in assessing dnDSA risk.MethodsOne-hundred-and-three HLA-DP-mismatched SOT pairs were retrospectively analysed. MM was computed using amino acids (aa), eplets and, supplementarily, Grantham/Epstein scores. DPB1 alleles were classified as rs9277534-A (low-expression) or -G (high-expression)–linked. To determine the associations between risk factors and dnDSA, logistic regression, linkage disequilibrium (LD) and population-based analyses were performed.ResultsA high-risk AA:GX (recipient:donor) expression combination (X=A or G) demonstrated strong association with DP-dnDSA (p=0.001). MM was also associated with DP-dnDSA when evaluated by itself (eplet_p=0.007, aa_p=0.003, Grantham_p=0.005, Epstein_p=0.004). When attempting to determine the relative individual effects of the risk factors in multivariable analysis, only AA:GX expression status retained a strong association (RR=18.6, p=0.007 with eplet; RR=15.8, p=0.02 with aa), while MM was no longer significant (eplet_p=0.56, aa_p=0.51). Importantly, these risk factors are correlated, due to LD between the expression-tagging SNP and polymorphisms along HLA-DPB1.ConclusionsThe MM and expression risk factors each appear to be strong predictors of DP-dnDSA and to possess clinical utility; however, the two risk factors are closely correlated. These metrics may represent distinct ways of characterizing a common overlapping dnDSA risk profile, but they are not independent. Further, we demonstrate the importance and detailed implications of LD effects in risk assessment of dnDSA and possibly transplantation overall.

scholarly journals Risk Factors for Failure of Primary (Val)ganciclovir Prophylaxis Against Cytomegalovirus Infection and Disease in Solid Organ Transplant Recipients

2019 ◽  
Vol 6 (6) ◽  
Author(s):  
Mark P Khurana ◽  
Isabelle P Lodding ◽  
Amanda Mocroft ◽  
Søren S Sørensen ◽  
Michael Perch ◽  
...  
Keyword(s):  
Risk Factors ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Primary Prophylaxis ◽  
Solid Organ ◽  
Post Transplantation ◽  
Cox Models ◽  
Optimal Dosing ◽  
Increased Risk ◽  
Accurate Dose

Abstract Background Rates and risk factors for cytomegalovirus (CMV) prophylaxis breakthrough and discontinuation were investigated, given uncertainty regarding optimal dosing for CMV primary (val)ganciclovir prophylaxis after solid organ transplantation (SOT). Methods Recipients transplanted from 2012 to 2016 and initiated on primary prophylaxis were followed until 90 days post-transplantation. A (val)ganciclovir prophylaxis score for each patient per day was calculated during the follow-up time (FUT; score of 100 corresponding to manufacturers’ recommended dose for a given estimated glomerular filtration rate [eGFR]). Cox models were used to estimate hazard ratios (HRs), adjusted for relevant risk factors. Results Of 585 SOTs (311 kidney, 117 liver, 106 lung, 51 heart) included, 38/585 (6.5%) experienced prophylaxis breakthrough and 35/585 (6.0%) discontinued prophylaxis for other reasons. CMV IgG donor+/receipient- mismatch (adjusted HR [aHR], 5.37; 95% confidence interval [CI], 2.63 to 10.98; P &lt; 0.001) and increasing % FUT with a prophylaxis score &lt;90 (aHR, 1.16; 95% CI, 1.04 to 1.29; P = .01 per 10% longer FUT w/ score &lt;90) were associated with an increased risk of breakthrough. Lung recipients were at a significantly increased risk of premature prophylaxis discontinuation (aHR, 20.2 vs kidney; 95% CI, 3.34 to 121.9; P = .001), mainly due to liver or myelotoxicity. Conclusions Recipients of eGFR-adjusted prophylaxis doses below those recommended by manufacturers were at an increased risk of prophylaxis breakthrough, emphasizing the importance of accurate dose adjustment according to the latest eGFR and the need for novel, less toxic agents.

scholarly journals Solid Organ Transplantation (SOT) and Data Mining: Bloodstream Infections (BSI) Have a Significant Impact on One-Year Survival, and qSOFA ≥ 2 Predicts 30-Day Mortality

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S10-S10
Author(s):  
Terrence Liu ◽  
Donglu Xie ◽  
Beverley Adams-Huet ◽  
Jade Le ◽  
Christina Yek ◽  
...  
Keyword(s):  
Risk Factors ◽  
Data Mining ◽  
Cumulative Incidence ◽  
Multivariable Analysis ◽  
Solid Organ Transplantation ◽  
Common Source ◽  
Solid Organ ◽  
Risk Of Death ◽  
Increased Risk ◽  
Mining Tools

Abstract Background We created a retrospective and prospective database of SOT recipients using innovative data mining tools. This study describing the epidemiology of BSI in SOT serves as a proof of concept of such techniques in clinical research. Methods The design of the study was a retrospective, single-center, cohort study. Data mining tools were used to extract information from the electronic medical record and merged it with data from the SRTR (Figure 1). First SOT from January 1, 2010 to December 31, 2015 were included. Charts of subjects with positive blood cultures were manually reviewed and adjudicated using CDC/NHSN and SCCM/ESICM criteria. The 1-year cumulative incidence was calculated using the Kaplan–Meier method. Cox proportional hazards models were used to identify risk factors for BSI and 1-year mortality. BSI was analyzed as a time-dependent covariate in the mortality model. Fisher’s exact test and chi-square were used to identify risk factors for 30-day mortality and MDRO. Results A total of 917 SOT recipients met inclusion criteria. Seventy-five patients experienced at least one BSI. The cumulative incidence was 8.4% (95% CI 6.8–10.4) (Figure 2). The onset of the first BSI episode was: 30 episodes (40%) &lt;1 month, 33 (44%) 1–6 months, and 12 (16%) &gt;6 months. The most common pathogens were Klebsiella sp. (16%), Vancomycin-resistant E. faecium (12%), E. coli (12%), CoNS (12%), and Candida sp. (9.3%). Nineteen isolates (25%) were identified as MDRO; the risk of MDRO was highest &lt;1 month compared with 1–6 and &gt;6 months (44.8 vs. 12.1 vs. 16.7; P = 0.01). The most common source of BSI was CLABSI (29%) (Figure 3). In multivariable analysis, the risk of BSI was associated with organ type (HR [95% CI] = Multiorgan 3.5 [1.1–11.6], liver 2.5 [1.1–5.4], heart 2.4 [1.1–5.1]) and acquisition of a BSI was associated with a higher 1-year mortality (HR = 8.7 [5.1–14.7]). In univariable analysis, a polymicrobial BSI (14.7 vs. 57.1%; P = 0.02), qSOFA ≥ 2 (0.0 vs. 25.5%; P = 0.02) and septic shock (3.9 vs. 52.2%; P &lt; 0.001) were associated with an increased risk of death at 30 days. Conclusion A BSI significantly affects the 1-year survival of SOT recipients. A qSOFA ≥ 2 can be used to identify patients at risk for death. Additionally, this study illustrates the potential of data mining tools to study infectious complications. Disclosures All authors: No reported disclosures.

scholarly journals Risk Factors for Extended-Spectrum β-lactamase–Producing Enterobacterales Bloodstream Infection Among Solid-Organ Transplant Recipients

2020 ◽  
Author(s):  
Judith A Anesi ◽  
Ebbing Lautenbach ◽  
Pranita D Tamma ◽  
Kerri A Thom ◽  
Emily A Blumberg ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariable Analysis ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Johns Hopkins Hospital ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Organ Transplant Recipients ◽  
Extended Spectrum ◽  
Solid Organ Transplant Recipients

Abstract Background Approximately 40% of all Enterobacterales (EB) bloodstream infections (BSIs) among solid organ transplant recipients (SOTRs) are due to extended-spectrum β-lactamase (ESBL)–producing organisms, but risk factors for such infections remain ill defined in this population. We sought to determine the risk factors for ESBL-EB BSIs among SOTRs. Methods A multicenter case-control study was performed. All SOTRs with an EB BSI at the Hospital of the University of Pennsylvania and University of Maryland Medical Center between 1 January 2007 and 30 June 2018 and at The Johns Hopkins Hospital between 1 January 2005 and 31 December 2015 were included. Cases were those with an ESBL-EB BSI. Controls were those with a non–ESBL-EB BSI. Multivariable logistic regression was performed to determine risk factors for ESBL-EB BSI. Results There were 988 episodes of EB BSI, of which 395 (40%) were due to an ESBL-EB. On multivariable analysis, the independent risk factors for ESBL-EB BSI included: ESBL-EB on prior culture (aOR, 12.75; 95% CI, 3.23–50.33; P &lt; .001), a corticosteroid-containing immunosuppression regimen (aOR 1.30; 95% CI 1.03–1.65; P = .030), acute rejection treated with corticosteroids (aOR 1.18; 95% CI 1.16–1.19; P &lt; .001), and exposure to third-generation cephalosporins (aOR 1.95; 95% CI 1.48–2.57; P &lt; .001), echinocandins (aOR 1.61; 95% CI 1.08–2.40; P = .020), and trimethoprim-sulfamethoxazole (aOR 1.35; 95% CI 1.10–1.64; P = .003). Conclusions We identified several novel risk factors that are uniquely important to the SOTR population, including exposure to trimethoprim-sulfamethoxazole and corticosteroid-containing immunosuppressive regimens. Further studies exploring these associations and testing interventions aimed at these modifiable risk factors among SOTRs are needed.

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.

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