Infections In Solid Organ Transplant Recipients Research Articles

An exploratory analysis of C-X-C motif chemokine ligand 10 as a new biomarker of asymptomatic Leishmania infantum infection in solid-organ transplant recipients

Sensitive and less laborious assays are needed to detect asymptomatic Leishmania among solid organ transplant (SOT) recipients. Using SLA-stimulated plasma from SOT recipients living where an outbreak of Leishmania infantum occurred, we examined potential biomarkers to identify asymptomatic Leishmania infections. Concentrations of cytokines/chemokines in plasma from whole blood stimulated with specific Leishmania antigen (SLA) were compared against infection status as determined by a currently used cell proliferation assay. Twenty-six percent (13/50) of the SOT recipients had a cell proliferation assay (CPA) indicating asymptomatic infection, and showed higher processed plasma C-X-C motif chemokine ligand 10 (CXCL10 or IP-10) concentrations than did non-infected subjects (median 2272.0 pg/ml [IQR 1570-2772] vs. 18.2 pg/ml [IQR 1-150.1]; p<0.0001). CXCL10 showed a sensitivity of 93% and a specificity of 95% compared to CPA. In addition, we demonstrated that the number of asymptomatic infections detected using CXCL10, decreased with distance from a park at the center of the mentioned outbreak. CXCL10 in plasma from SLA-stimulated blood could be a robust biomarker of asymptomatic L. infantum infection in solid organ transplant recipients.

Epidemiology and outcomes of medically attended and microbiologically confirmed bacterial foodborne infections in solid organ transplant recipients

Food‐safety measures are recommended to solid organ transplant (SOT) recipients. However, the burden of foodborne infections in SOT recipients has not been established. We describe the epidemiology and outcomes of bacterial foodborne infections in a nationwide cohort including 4405 SOT recipients in Switzerland between 2008 and 2018. Participants were prospectively followed for a median of 4.2 years with systematic collection of data on infections, and patient and graft‐related outcomes. We identified 151 episodes of microbiologically confirmed bacterial foodborne infections occurring in median 1.6 years (IQR 0.58–3.40) after transplantation (131 [88%] Campylobacter spp. and 15 [10%] non‐typhoidal Salmonella). The cumulative incidence of bacterial foodborne infections was 4% (95% CI 3.4–4.8). Standardized incidence rates were 7.4 (95% CI 6.2–8.7) and 4.6 (95% CI 2.6–7.5) for Campylobacter and Salmonella infections, respectively. Invasive infection was more common with Salmonella (33.3% [5/15]) compared to Campylobacter (3.2% [4/125]; p = .001). Hospital and ICU admission rates were 47.7% (69/145) and 4.1% (6/145), respectively. A composite endpoint of acute rejection, graft loss, or death occurred within 30 days in 3.3% (5/151) of cases. In conclusion, in our cohort bacterial foodborne infections were late post‐transplant infections and were associated with significant morbidity, supporting the need for implementation of food‐safety recommendations.

Occurrence of Severe SARS-CoV-2 Infection in Fully Vaccinated Solid Organ Transplant Recipients

The present study presents the clinical outcome of SARS-CoV-2 disease in relation to the humoral response in fully vaccinated solid organ transplant (SOT) recipients. Our patient cohort consists of 455 SOT recipients, vaccinated with one of the 2 approved mRNA vaccines. The antibody response was measured 1 month after the second dose, and previously infected patients have been excluded. Of the 449 remaining patients, 15 (3.34%) tested positive, using SARS-CoV-2 polymerase chain reaction. Their mean age was 43.7 ±14.4 years, and median time from transplantation was 7.8 years (1.2-30.2). Eleven patients (73.3%) had been vaccinated with BNT162b2 and 4 (26.7%) with the mRNA1273 vaccine. At the time of infection 9 (60%) patients had a negative (<50 AU/mL) antibody titer, and 6 (40%) had a positive one (>50 AU/mL). Median antibody titer, 27.4± 14.0 days after the second dose, measured at 13 AU/mL (0-7480 AU/mL). Renal function did not appear to be affected by the disease. Τhe mean estimated glomerular filtration rate at diagnosis was 48 ± 15 mL/min, and when in a 29-day (1-101) median follow-up was 53.9± 20.9 mL/min. Of the 15 patients, 7 had mild symptoms and were not hospitalized, and of the remaining 8 (53.3%) who needed hospitalization 7 had severe disease and 2 of them expired. The study confirms the variable and often severe course of coronavirus 2019 infection in SOT recipients, even after their full vaccination, highlighting the need to vaccinate their close relatives and to accelerate the implementation of the booster dose of vaccine.

COVID-19 in Solid Organ Transplant Recipient: Exploring Cumulative Incidence, Seroprevalence and Risk Factors for Disease Severity.

Simple SummaryIt is still uncertain whether recipients of solid organ transplant (SOT) are at increased risk of SARS-CoV-2 infection and/or poor outcomes due to COVID-19 in comparison to the general population. In this study, we report the cumulative incidence and outcomes of SARS-CoV-2 infection in a cohort of 291 SOT recipients. The COVID-19 cumulative incidence in SOT recipients resulted slightly higher compared to that of age-matched population during the study period. Moreover, the SARS-CoV-2 antibody frequency was around 2.6-fold higher than the incidence of cases who tested positive for SARS-CoV-2 RT-PCR, suggesting that the number of SOT recipients infected with SARS-CoV-2 is likely higher than described. In symptomatic recipients, kidney transplant was associated with a higher risk of developing moderate/critical disease, while common risk factors, including age and comorbidities, resulted less relevant for COVID-19 severity. Due to the high estimated crude mortality, symptomatic SOT recipients should be considered at high risk in case of SARS-CoV-2 infection.Background: Solid organ transplant (SOT) recipients may be at increased risk for severe disease and mortality from COVID-19 because of immunosuppression and prolonged end-stage organ disease. As a transplant center serving a diverse patient population, we report the cumulative incidence and outcomes of SARS-CoV-2 infection in our cohort of SOT recipients. Methods: We prospectively included in this observational study SOT recipients with a functioning kidney (n = 201), pancreas ± kidney (n = 66) or islet transplant (n = 24), attending outpatient regular follow-up at the San Raffaele Hospital from February 2020 to April 2021. Antibodies to SARS-CoV-2 were tested in all patients by a luciferase immunoprecipitation system assay. Results: Of the 291 SOT recipients, 30 (10.3%) tested positive for SARS-CoV-2 during the study period and prevalence was not different among different transplants. The SARS-CoV-2 antibody frequency was around 2.6-fold higher than the incidence of cases who tested positive for SARS-CoV-2 RT-PCR. As for the WHO COVID-19 severity classification, 19 (63.3%) SOT recipients were mild, nine (30%) were moderate, and two were critical and died yielding a crude mortality rate in our patient population of 6.7%. Kidney transplant (OR 12.9 (1.1–150) p = 0.041) was associated with an increased risk for moderate/critical disease, while statin therapy (OR 0.116 (0.015–0.926) p = 0.042) and pancreas/islet transplant (OR 0.077 (0.007–0.906) p = 0.041) were protective. Conclusions: The incidence of SARS-CoV-2 infection in SOT recipients may be higher than previously described. Due to the relative high crude mortality, symptomatic SOT recipients must be considered at high risk in case of SARS-CoV-2 infection.

545. A Retrospective Review of 30-day Mortalities in Solid-Organ Transplant Recipients (SOT) versus Non-Transplant Patients (NTP) Receiving Remdesivir (REM) and Dexamethasone (DEX) for COVID-19 Pneumonia

BackgroundTreating COVID-19 infection in SOT is challenging due to long-term use of immunosuppressive agents. REM is the only FDA-approved anti-viral for SARS-COV-2 infection. DEX showed decrease in mortality in the Recovery Trial. COVID-19 treatment guidelines for SOT patients are the same as NTP despite limited literature on those outcomes. Our primary objective was to determine if 30-day mortality was different between SOT and NTP matched cohorts using these 2 drugs. The secondary objectives included comparisons of length of stay (LOS), days on mechanical ventilation (DMV), and the use of other treatment modalities.MethodsWe retrospectively collected data for hospitalized SOT and NTP, 18 years and older, with pcr-confirmed SARS-CoV-2 infection receiving REM and DEX from May 1, 2020, to October 10, 2020, at Mayo Clinic Florida. IRB approval was obtained. Descriptive statistics were used to analyze the data. Continuous variables were summarized as mean (standard deviation) or median (range) where appropriate, while categorical variables were reported as frequency (percentage).ResultsOf 80 patients who met the inclusion criteria, 28 were SOT, and 52 were NTP. The SOT cohort was subcategorized below:CharacteristicsNumber of SOT (n = 28)Transplant TypeKidney n (%)15 (53.7)Lung n (%)3 (10.7)Liver n (%)2 (7.1)Heart n (%)6 (21.4)Multi-organ n (%)2 (7.1)SOT patients were significantly younger than NTP (p < .001). Further, SOT patients had significantly longer LOS (p = 0.043) and more COVID-19 modalities (75% vs. 36.5%, p = 0.002) compared to NTP. Among the 28 SOT patients, 2 of them died within 30 days of admission, and among the 52 NTP patients, 7 of them died within 30 days. The 30-d survival estimate for SOT group is 92.9% (95% CI: 83.8% - 100.0%) and for NTP group is 86.5% (95% CI: 77.7% - 96.3%). The log-rank test was not significant between the groups (p=0.37), but the NTP has a worse survival curve from the figure below.SOT-NTP Survival Curve ConclusionSOT group was younger, had longer LOS, and more COVID-related modalities. The 30-d survival estimate for SOT group is 92.9% and for NTP group is 86.5%, but the survival curve for NTP was worse likely secondary to age. Use of REM & DEX in SOT recipients is a valid recommendation.Disclosures Claudia R. Libertin, MD, Gilead (Grant/Research Support)

111. Assessment of Empiric Management Practices of Common Infections in Solid Organ Transplant Recipients at a Canadian Tertiary Care Centre - A Retrospective Cohort Study

BackgroundPost-transplant infections remain a leading cause of morbidity and mortality in solid organ transplant recipients (SOTR). Standardized antimicrobial treatment guidelines for infectious syndromes may contribute to improved clinical care. Our study seeks to assess the rate of therapeutic compliance with local standard guidelines in the treatment of common infections in SOTR, and their associated outcomes.MethodsConsecutive adult SOTR admitted to the transplant floor from January–May 2020 for treatment of an infectious syndrome of interest were reviewed for study inclusion. Patients were followed until discharge or for 30 days following the date of diagnosis, whichever was shorter. Data was extracted from electronic medical records.Results475 SOTR were admitted to the transplant floor, of which 156 patients (33%) were admitted with infectious syndromes. Guidelines were applicable to 117 patients, constituting the following 122 syndromes: 51 pneumonias; 34 urinary tract infections (UTI); 22 bacteremias and 15 intra-abdominal infections (Fig. 1). Intra-abdominal infections occurred earliest at a median time of 9 months post-transplant followed by bacteremias, pneumonias, and UTIs (medians 10, 38 and 54 months respectively) (Table 1). 47% of patients were empirically treated with a regimen compliant with guidelines and 66% were provided compliant tailored therapies. Non-compliance with empiric management guidelines resulted in a significantly higher proportion of patients requiring ICU transfer when compared to compliance (25% vs. 9%; P = .02) (Table 2). Non-compliance with tailoring protocols resulted in an increased overall length of stay (medians 11 days vs. 8 days; P = .04). Within 30 days of discharge, no differences in readmission, development of Clostridium difficile infection, rejection, graft loss or death were observed between patients receiving compliant or non-compliant regimens.Figure 1. Study Flow Diagram Table 1. Baseline Characteristics of Patient Cohort Table 2. Outcomes of compliant vs. non-compliant treatment in patients receiving antimicrobial therapy for an infectious syndrome ConclusionNon-compliance with locally developed antimicrobial management guidelines resulted in a higher proportion of patients being transferred to the ICU and an increased length of stay in our cohort, highlighting the benefits of adherence. Future studies will assess long-term outcomes associated with compliance to infection management guidelines.Disclosures All Authors: No reported disclosures

Clinical Features of SARS-CoV-2 Infection in Patients Undergoing Solid-Organ Transplant: Baskent University Experience.

The clinical features and treatment approaches, outcomes, and mortality predictors of COVID-19 in solid-organ transplant recipients have not been well defined. This study investigated the clinical features of COVID-19 infection in solid-organ transplant recipients at our center in Turkey. Our study included 23 solidorgan transplant recipients and 336 nontransplant individuals (143 previously healthy and 193 patients with at least 1 comorbidity) who were hospitalized due to COVID-19 disease in our hospital between March 2020 and January 2021. Demographic, clinical, and laboratory data of patients were compared. We used SPSS version 20.0 for statistical analysis. All groups were compared using chi-square and Mann-Whitney U tests. P <.05 was considered statistically significant. Mean age of solid-organ transplant recipients was 49.8 ± 13.7 years (78.3% men, 21.7% women). Among the 23 recipients, 17 (73.9%) were kidney and 6 (26.1%) were liver transplant recipients. Among nontransplant individuals, 88.7% (n = 298) had mild/moderate disease and 11.3% (n = 38) had severe disease. Among transplant recipients, 78.3% (n = 18) had mild/moderate disease and 21.7% (n = 5) had severe disease (P = .224). Transplant recipients had greater requirements for nasal oxygen (P = .005) and noninvasive mechanical ventilation (P = .003) and had longer length of intensive care unit stay (P = .030) than nontransplant individuals. No difference was found between the 2 groups in terms of mortality (P = .439). However, a subgroup analysis showed increased mortality in transplant recipients versus previously healthy patients with COVID-19 (P <.05). Secondary infections were major causes of mortality in transplant recipients. COVID-19 infection resulted in higher mortality in solid-organ transplant recipients versus that shown in healthy patients. More attention on secondary infections is needed in transplant recipients to reduce mortality.

An Observational Prospective Cohort Study of Incidence and Outcome of Streptococcus pneumoniae and Hemophilus influenzae Infections in Adult Solid Organ Transplant Recipients.

Background: Streptococcus pneumoniae (S. pneumoniae) and Hemophilus influenzae (H. influenzae) are among the main vaccine-preventable bacterial infections in immunocompromised individuals including solid organ transplant (SOT) recipients. There is a lack of information about incidence and outcomes of these infections in SOT recipients. Methods: We determined the incidence of S. pneumoniae and H. influenzae, the related hospitalization, and 30- and 180-days mortality in a large cohort of 1182 adult SOT recipients. We calculated 95% confidence intervals (CI) of incidence rate (IR) using Byar’s approximation to the Poisson distribution. Results: The overall IR of S. pneumoniae and H. influenzae were 1086 (95% CI, 796–1448) and 1293 (95% CI, 974–1687) per 100,000 person-years of follow-up (PYFU), respectively. The IR of invasive infections were 76 (95% CI, 21–202) and 25 (95% CI, 2.3–118) per 100,000 PYFU, respectively. Hospital admission was required in >50%, 30-days mortality was 0, and 180-days mortality was 8.8% and 4.5% after S. pneumoniae and H. influenzae infections, respectively. Conclusions: The IR of invasive S. pneumoniae and H. influenzae infections in SOT recipients were much higher than reports from the general population in Denmark. Furthermore, a large proportion of infected SOT recipients were hospitalized. These findings highlight the need for further studies to assess uptake and immunogenicity of vaccines against S. pneumoniae and H. influenzae in SOT recipients.

Infections in the solid-organ transplant recipients

The advancement in the field of transplant has led to the increasing number of solid-organ transplant recipients (SOTRs). This success leads to novel confronts in communicable infections, which are compound by the emergence of newly contagious and antimicrobial drugs resistant microorganisms. The prevention of infections is a cornerstone of any modern solid organ transplantation program. Understanding the fundamentals of these infections with early detection is crucial for improving the outcomes of such patients and lowers the probable extra complications. The probability of critical infections in SOTRs is established by relations between the patient’s epidemiological exposures and the net condition of immune repression. A timeline was formed to build up a discrepancy diagnosis of infection in SORTs. The improvement in screening, the investigations including imaging and molecular techniques and prophylactic intervention protocols, has made it promising to limit the penalty of infections and act towards better patient endurance. Pre-transplant screening of the prospective organ donor and recipient provides a chance to evaluate the viability and wellbeing of transplantation, to decide the prophylaxis and protective approaches developed post-transplant, to find out and entirely treat active infection in the possible recipient proceeding to transplant, to renovate the vaccination condition of the potential recipient.

Hepatitis E in solid organ transplant recipients: A systematic review and meta-analysis.

BACKGROUNDHepatitis E virus (HEV) infection is underdiagnosed due to the use of serological assays with low sensitivity. Although most patients with HEV recover completely, HEV infection among patients with pre-existing chronic liver disease and organ-transplant recipients on immunosuppressive therapy can result in decompensated liver disease and death.AIMTo demonstrate the prevalence of HEV infection in solid organ transplant (SOT) recipients. METHODSWe searched Ovid MEDLINE, EMBASE, and the Cochrane Library for eligible articles through October 2020. The inclusion criteria consisted of adult patients with history of SOT. HEV infection is confirmed by either HEV-immunoglobulin G, HEV-immunoglobulin M, or HEV RNA assay.RESULTSOf 563 citations, a total of 22 studies (n = 4557) were included in this meta-analysis. The pooled estimated prevalence of HEV infection in SOT patients was 20.2% [95% confidence interval (CI): 14.9-26.8]. The pooled estimated prevalence of HEV infection for each organ transplant was as follows: liver (27.2%; 95%CI: 20.0-35.8), kidney (12.8%; 95%CI: 9.3-17.3), heart (12.8%; 95%CI: 9.3-17.3), and lung (5.6%; 95%CI: 1.6-17.9). Comparison across organ transplants demonstrated statistical significance (Q = 16.721, P = 0.002). The subgroup analyses showed that the prevalence of HEV infection among SOT recipients was significantly higher in middle-income countries compared to high-income countries. The pooled estimated prevalence of de novo HEV infection was 5.1% (95%CI: 2.6-9.6) and the pooled estimated prevalence of acute HEV infection was 4.3% (95%CI: 1.9-9.4).CONCLUSIONHEV infection is common in SOT recipients, particularly in middle-income countries. The prevalence of HEV infection in lung transplant recipients is considerably less common than other organ transplants. More studies examining the clinical impacts of HEV infection in SOT recipients, such as graft failure, rejection, and mortality are warranted.

#76: Epidemiology of Cytomegalovirus (CMV) in Pediatric Solid-Organ Transplant Recipients (SOTR) at Texas Children’s Hospital (TCH)

Abstract Background Despite the widespread use of prevention strategies, CMV remains a common opportunistic infection in SOTR. Contemporary data regarding CMV in pediatric SOTR are limited. We sought to determine the frequency of and risk factors for CMV infection and disease in a large single-center cohort of pediatric SOTR. Methods A retrospective cohort study of patients &amp;lt;22 years of age who received lung, heart, liver, kidney, or multi-organ transplants at TCH between 2010 and 2018 was completed. Universal CMV prophylaxis was used based on risk status (Figure 1). The primary outcome was quantifiable CMV DNAemia. Associations with CMV DNAemia were measured using Fisher exact, Kruskal–Wallis, and multivariate logistic regression. Survival analysis and time to CMV infection were assessed using Kaplan–Meier plots. Results Among 788 SOTR, 132 (17%) had quantifiable CMV DNAemia; this included 20/105 (19%) lung, 69/290 (24%) liver, 28/178 (16%) heart, 2/15 (13%) multi-organ, and 13/200 (7%) kidney recipients. Fifty-one (6%) SOTR had CMV DNAemia while on antiviral prophylaxis. Post-prophylaxis, 69 (9%) SOTR had CMV reactivation and 12 (2%) had primary infection. The median time to quantifiable DNAemia for patients that developed CMV was 290 days post-transplant for lung, 162 for liver, 186 for heart, and 294 for kidney (P &amp;lt; 0.01), reflecting differences in prophylaxis strategies. High-risk CMV status (D+/R– for heart, liver, kidney, and D+ and/or R+ for lung) was associated with CMV DNAemia (P &amp;lt; 0.01). Type of organ transplanted also showed an association with CMV DNAemia (P = 0.02) with liver transplant recipients more being more likely to have a positive CMV PCR. DNAemia was not associated with age at transplantation, type of organ, or the use of induction immunosuppression. There was no difference in survival during the study follow-up period (1–9 yr) for SOTR with vs. without DNAemia (P = 0.48). Overall, 22/788 (3%) SOTR had CMV disease, 3 (3%) lung, 4 (2%) heart, 8 (3%) liver, 1 (6%) multi-organ, and 6 (3%) kidney recipients. Twenty had CMV syndrome and 2 had tissue invasive disease. Median (range) maximum viral loads were 27700 IU/mL (233-3912694) for SOTR with vs. 900 IU/mL (26-112000) for SOTR without CMV disease (P &amp;lt; 0.01). Conclusion This large contemporary cohort of pediatric SOTR on universal prophylaxis demonstrates low overall rates of CMV DNAemia and CMV disease. High-risk CMV status remains associated with CMV DNAemia, suggesting that further interventions targeting this group may be warranted.

Central nervous system infections after solid organ transplantation

Significant advances to our understanding of several neuroinfectious complications after a solid organ transplant (SOT) have occurred in the last few years. Here, we review the central nervous system (CNS) infections that are relevant to SOT via a syndromic approach with a particular emphasis on recent updates in the field. A few key studies have advanced our understanding of the epidemiology and clinical characteristics of several CNS infections in SOT recipients. Risk factors for poor prognosis and protective effects of standard posttransplant prophylactic strategies have been better elucidated. Newer diagnostic modalities which have broad clinical applications like metagenomic next-generation sequencing, as well as those that help us better understand esoteric concepts of disease pathogenesis have been studied. Finally, several studies have provided newer insights into the treatment of these diseases. Recent findings reflect the steady progress in our understanding of CNS infections post SOT. They provide several avenues for improvement in the prevention, early recognition, and therapeutic outcomes of these diseases.

Tedizolid vs Linezolid for the Treatment of Nontuberculous Mycobacteria Infections in Solid Organ Transplant Recipients

BackgroundTreatment options for nontuberculous mycobacteria (NTM) infections are limited by the pathogen’s intrinsic resistance profile and toxicities. Tedizolid and linezolid display in vitro activity against NTM species. However, safety data and treatment outcomes are limited in the solid organ transplant (SOT) population.MethodsThis was a single-center retrospective cohort study of adult SOT recipients receiving linezolid or tedizolid for an NTM infection from January 1, 2010, to August 31, 2019. The primary outcome compared the hematologic safety profiles of tedizolid vs linezolid. We also described nonhematological adverse drug events (ADEs) and therapy discontinuation rates. In an exploratory analysis, we assessed symptomatic microbiologic and clinical outcomes in those receiving tedizolid or linezolid for at least 4 weeks.ResultsTwenty-four patients were included (15 tedizolid, 9 linezolid). No differences were identified comparing the effects of tedizolid vs linezolid on platelet counts, absolute neutrophil counts (ANCs), and hemoglobin over 7 weeks using mixed-effects analysis of variance models. ANC was significantly decreased in both groups after 7 weeks of therapy (P = .04). Approximately 20% of patients in each arm discontinued therapy due to an ADE. Seven of 12 (58%) and 2 of 3 (67%) patients were cured or clinically cured with tedizolid- and linezolid-containing regimens, respectively.ConclusionsThis study suggests no significant safety benefit of tedizolid over linezolid for the treatment of NTM infections in SOT recipients. Tedizolid or linezolid-containing regimens demonstrated a potential benefit in symptomatic and microbiologic improvement. Larger cohorts are needed to further delineate the comparative role of linezolid and tedizolid for the treatment of NTM infections in SOT recipients.

Inpatient COVID-19 outcomes in solid organ transplant recipients compared to non-solid organ transplant patients: A retrospective cohort.

Immunosuppression and comorbidities might place solid organ transplant (SOT) recipients at higher risk from COVID-19, as suggested by recent case series. We compared 45 SOT vs. 2427 non-SOT patients who were admitted with COVID-19 to our health-care system (March 1, 2020 - August 21, 2020), evaluating hospital length-of-stay and inpatient mortality using competing-risks regression. We compared trajectories of WHO COVID-19 severity scale using mixed-effects ordinal logistic regression, adjusting for severity score at admission. SOT and non-SOT patients had comparable age, sex, and race, but SOT recipients were more likely to have diabetes (60% vs. 34%, p<.001), hypertension (69% vs. 44%, p=.001), HIV (7% vs. 1.4%, p=.024), and peripheral vascular disorders (19% vs. 8%, p=.018). There were no statistically significant differences between SOT and non-SOT in maximum illness severity score (p=.13), length-of-stay (sHR: 0.9 1.11.4 , p=.5), or mortality (sHR: 0.1 0.41.6 , p=.19), although the severity score on admission was slightly lower for SOT (median [IQR] 3 [3, 4]) than for non-SOT (median [IQR] 4 [3-4]) (p=.042) Despite a higher risk profile, SOT recipients had a faster decline in disease severity over time (OR = 0.76 0.810.86 , p<.001) compared with non-SOT patients. These findings have implications for transplant decision-making during the COVID-19 pandemic, and insights about the impact of SARS-CoV-2 on immunosuppressed patients.

Incidence and outcome of SARS-CoV-2 infection on solid organ transplantation recipients: A nationwide population-based study.

Since February 21 2020, when the Italian National Institute of Health (Istituto Superiore di Sanità-ISS) reported the first autochthonous case of infection, a dedicated surveillance system for SARS-CoV-2-positive (COVID+) cases has been created in Italy. These data were cross-referenced with those inside the Information Transplant System in order to assess the cumulative incidence (CI) and the outcome of SARS-COV-2 infection in solid organ transplant recipients (SOTRs) who are assumed to be most at risk. We compared our results with those of COVID+ nontransplanted patients (Non-SOTRs) with follow-up through September 30, 2020. The CI of SARS-CoV-2 infection in SOTRs was 1.02%, higher than in COVID+ Non-SOTRs (0.4%, p<.05) with a greater risk in the Lombardy region (2.89%). The CI by type of organ transplant was higher for heart (CI 1.57%, incidence rate ratio [IRR] 1.36) and lower for liver (CI 0.63%, IRR 0.54). The 60-day CI of mortality was 30.6%, twice as much that of COVID+ Non-SOTRs (15.4%) with a 60-day gender and age adjusted odds ratio (adjusted-OR) of 3.83 for COVID+ SOTRs (95% confidence interval [3.03-4.85]). The lowest 60-day adjusted-OR was observed in liver SOTRs (OR 0.46, 95% confidence interval [0.25-0.86]). More detailed studies on disease management and evolution will be necessary in these patients at greater risk of COVID-19.

1096. Linezolid versus Tedizolid for the Treatment of Nontuberculous Mycobacteria in Solid Organ Transplant Recipients: An Assessment of Safety

BackgroundTreatment options for nontuberculous mycobacteria (NTM) infections are limited by the long-term tolerability of antimicrobials. The oxazolidinones, linezolid and tedizolid, display in vitro activity against many NTM species and demonstrate excellent oral bioavailability. This study compares the hematologic safety profile of linezolid versus tedizolid for the treatment of NTM in solid organ transplant (SOT) recipients.MethodsThis retrospective cohort study included adult SOT recipients who received linezolid or tedizolid as part of a multi-drug regimen to treat NTM between January 1, 2010 to August 31, 2019. The primary endpoint was the hematologic effects of linezolid versus tedizolid from therapy initiation to week seven. This time frame was chosen based on the median duration of therapy. A mixed-effects ANOVA model was used to assess the effects of linezolid and tedizolid on platelet counts (PLT), absolute neutrophil counts (ANC), and hemoglobin (Hgb) across time. Subjects were treated as a random effect. The secondary analysis described the proportion of adverse effects and discontinuation.ResultsTwenty-four patients were included in the analysis (9 linezolid, 15 tedizolid). Mycobacterium abscessus abscessus was the most common isolate, and pulmonary was the most common site of infection (Table 1). The median duration of therapy was 24 days (range 3 to 164 days) and 48 days (range 11 to 571 days) for linezolid and tedizolid, respectively. All patients in the linezolid group received 600 mg daily or less for the majority of treatment duration. In the mixed-effects ANOVA, the ANC decreased in both groups after seven weeks of therapy (p=0.04). Otherwise, no significant effects for week, treatment group, or interaction between week and treatment group were found (Figure 1). Thrombocytopenia and neutropenia were common in both groups, and around one-fifth of patients in each group discontinued the medication due to adverse effects (Table 2).Table 1. Baseline characteristics of solid organ transplant recipients who received linezolid or tedizolid as part of a multi-drug regimen to treat nontuberculous mycobacteria infections between January 1, 2010 to August 31, 2019 at UT Southwestern Medical Center. Table 2. Adverse drug events and discontinuation of therapy over seven weeks of therapy. Figure 1. Effects of linezolid versus tedizolid during the initial seven weeks of therapy using a mixed-effects ANOVA model, (a) platelet counts, (b) absolute neutrophil counts, and (c) hemoglobin. ConclusionNon-significant statistical differences were found comparing the effects of linezolid versus tedizolid for PLT, ANC, and Hgb using mixed-effects ANOVA models. Larger cohort studies are required to compare the hematologic adverse effect profile of the oxazolidinones for the treatment of NTM infections in SOT recipients.Disclosures All Authors: No reported disclosures

Outcomes of COVID-19 in Solid Organ Transplants

The novel coronavirus disease 2019 (COVID-19) is a global pandemic affecting millions of people worldwide. Solid organ transplant (SOT) recipients are probably at higher risk of severe infection and associated complications from COVID-19. Data on clinical outcomes of COVID-19 infection in SOT recipients are limited. Using the TriNetX database, patients with laboratory-confirmed COVID-19 from January 20, 2020, to July 7, 2020, were included in the study. We compared clinical outcomes comprising hospitalization, need for critical care services, intubation, and mortality among SOT recipients and patients without SOT. Of 30,573 laboratory-confirmed COVID-19 patients, 288 had SOT. Patients with SOT were more likely to be hospitalized (37.2% vs. 12.2%; p < 0.0001), needed critical care services (6.9% vs. 2.3%; p < 0.0001), needed intubation (7.9% vs. 2.0%; p < 0.0001), and had a higher 30-day mortality (11.1% vs. 3.8%; p < 0.0001). Patients in the transplant group were older (55.4 vs. 47.6 years; p < 0.0001) and had a higher prevalence of medical co-morbidities. SOT recipients are at significant risk of adverse COVID-19 related outcomes, including hospitalization, need for critical care services, and 30-day mortality, likely due to multiple co-morbid conditions.

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

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.

Update on Nocardia infections in solid-organ transplantation.

Nocardia is a ubiquitous pathogen associated with life-threatening opportunistic infections. Organ transplant recipients are uniquely predisposed to Nocardia infections due to their iatrogenic cell-mediated immune deficit necessary to maintain allograft function. This review aims to address recent updates in the epidemiology, clinical presentation, diagnostics, treatment, and outcomes of Nocardia infections in solid-organ transplant recipients. The incidence of Nocardia infection depends on multiple patient and environmental factors. Among transplant recipients, lung recipients are most commonly affected. Species identification and antimicrobial susceptibility testing are critical for optimizing therapy as substantial variation occurs among and within Nocardia spp. This has been increasingly accomplished through advances in molecular methods leading to improved accuracy and wider accessibility to testing. There are emerging data applying novel therapeutics and short course therapy that may offer alternative management approaches for transplant associated nocardiosis to minimize drug toxicity and intolerance. Further prospective, multicenter studies are needed to better characterize the epidemiology of Nocardia in transplant recipients, as well as evaluate the impact of diagnostic advancements and new treatment strategies.

Between fear and courage: Attitudes, beliefs, and behavior of liver transplantation recipients and waiting list candidates during the COVID-19 pandemic.

Patients with chronic liver disease and patients after solid organ transplantation (SOT) are vulnerable to severe coronavirus disease 2019 (COVID‐19). We evaluated fears, attitudes, and opinions associated with COVID‐19 in 365 SOT recipients (95% liver, 5% pancreas/kidney), 112 SOT candidates, and 394 immediate household contacts in 2 German transplant centers. Seven (1.5%) patients and 10 (2.5%) controls had contact with confirmed COVID‐19 cases. Fear of infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was expressed by 65% of SOT recipients and by 55% of SOT candidates. SOT recipients had higher levels of fear of infection and more often wore personal protective gear than household controls. Female sex, steroid treatment, and using the local newspaper as a primary source of information were independently associated with expressed fear of infection in SOT recipients. Younger age and more recent transplantation correlated with concerns about severe COVID‐19 expressed by patients and with concerns about worse medical care expressed by household controls. One third of the patients expressed fear that immunosuppression could worsen COVID‐19 but only 15% used the transplantation center as a source of information. These data show that fears associated with the SARS‐CoV‐2 pandemic are frequently expressed but measures to prevent infection are regularly followed by patients before and after SOT.