A hypervirulent (hvKp) pathotype is undergoing global dissemination. In contrast to the usual health care-associated epidemiology of classical (cKp) infections, hvKp causes tissue-invasive infections in otherwise healthy individuals from the community, often involving multiple sites. An accurate test to identify hvKp strains is needed for improved patient care and epidemiologic studies. To fill this knowledge gap, clinical criteria or random blood isolates from North American and United Kingdom strain collections were used to assemble hvKp-rich ( = 85) and cKp-rich ( = 90) strain cohorts, respectively. The isolates were then assessed for multiple candidate biomarkers hypothesized to accurately differentiate the two cohorts. The genes ,, , plasmid-borne gene ( ), and all demonstrated >0.95 diagnostic accuracy for identifying strains in the hvKp-rich cohort. Next, to validate this epidemiological analysis, all strains were assessed experimentally in a murine sepsis model. ,, ,, and were all associated with a hazard ratio of>25 for severe illness or death, additionally supporting their utility for identifying hvKp strains. Quantitative siderophore production of ≥30 μg/ml also strongly predicted strains as members of the hvKp-rich cohort (accuracy, 0.96) and exhibited a hazard ratio of 31.7 for severe illness or death. The string test, a widely used marker for hvKp strains, performed less well, achieving an accuracy of only 0.90. Last, using the most accurate biomarkers to define hvKp, prevalence studies were performed on two Western strain collections. These data strongly support the utility of several laboratory markers for identifying hvKp strains with a high degree of accuracy.
Despite clinical and laboratory screening of potential donors for transmissible disease, unexpected transmission of disease from donor to recipient remains an inherent risk of organ transplantation. The Disease Transmission Advisory Committee (DTAC) was created to review and classify reports of potential disease transmission and use this information to inform national policy and improve patient safety. From January 1, 2008 to December 31, 2017, the DTAC received 2185 reports; 335 (15%) were classified as a proven/probable donor transmission event. Infections were transmitted most commonly (67%), followed by malignancies (29%), and other disease processes (6%). Forty‐six percent of recipients receiving organs from a donor that transmitted disease to at least 1 recipient developed a donor‐derived disease (DDD). Sixty‐seven percent of recipients developed symptoms of DDD within 30 days of transplantation, and all bacterial infections were recognized within 45 days. Graft loss or death occurred in about one third of recipients with DDD, with higher rates associated with malignancy transmission and parasitic and fungal diseases. Unexpected DDD was rare, occurring in 0.18% of all transplant recipients. These findings will help focus future efforts to recognize and prevent DDD.
Mortality among patients hospitalized for COVID‐19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID‐19, we compared 28‐day mortality between early 2020 (March 1, 2020–June 19, 2020) and late 2020 (June 20, 2020–December 31, 2020). Multivariable logistic regression was used to assess comorbidity‐adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (
p
< .001). Crude 28‐day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46–0.98,
p
= .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%],
p
< .001 and 50/571 [8.8%] vs. 213/402 [52.2%],
p
< .001, respectively), and the use of hydroxychloroquine and IL‐6/IL‐6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%],
p
< .001 and 73/571 [12.8%] vs. 5/402 [1.2%],
p
< .001, respectively). Mortality among SOTR hospitalized for COVID‐19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study.
Transplant programs in the United States are encouraged to implement a monitoring program for heart transplant recipients with Chagas disease. Our experience using a preemptive approach of monitoring for Chagas disease reactivation was effective at identifying reactivation before symptoms developed.
Lung transplant recipients (LTR) with coronavirus disease 2019 (COVID‐19) may have higher mortality than non‐lung solid organ transplant recipients (SOTR), but direct comparisons are limited. Risk factors for mortality specifically in LTR have not been explored. We performed a multicenter cohort study of adult SOTR with COVID‐19 to compare mortality by 28 days between hospitalized LTR and non‐lung SOTR. Multivariable logistic regression models were used to assess comorbidity‐adjusted mortality among LTR vs. non‐lung SOTR and to determine risk factors for death in LTR. Of 1,616 SOTR with COVID‐19, 1,081 (66%) were hospitalized including 120/159 (75%) LTR and 961/1457 (66%) non‐lung SOTR (p = .02). Mortality was higher among LTR compared to non‐lung SOTR (24% vs. 16%, respectively, p = .032), and lung transplant was independently associated with death after adjusting for age and comorbidities (aOR 1.7, 95% CI 1.0–2.6, p = .04). Among LTR, chronic lung allograft dysfunction (aOR 3.3, 95% CI 1.0–11.3, p = .05) was the only independent risk factor for mortality and age >65 years, heart failure and obesity were not independently associated with death. Among SOTR hospitalized for COVID‐19, LTR had higher mortality than non‐lung SOTR. In LTR, chronic allograft dysfunction was independently associated with mortality.
On April 2021, the United States Organ Procurement and Transplantation Executive Committee approved the "lower respiratory SARS-CoV-2 testing for lung donors" emergency policy upon recommendation from the Ad Hoc Disease Transmission Advisory Committee. This policy requires that all lung donors be tested for SARS-CoV-2 in a lower respiratory specimen by nucleic acid test (NAT) and that the results be available before the lungs are transplanted. The overarching goal of the emergency policy was to minimize the risk of donor-derived COVID-19 to lung recipients. However, an unintended consequence of the policy was the emergence of a new population of potential donors: the SARS-CoV-2 lower respiratory tract (LRT) NAT positive donor. We describe the use of two SARS-CoV-2 LRT NAT positive liver donors without a known history of COVID-19 infection with adequate short-term outcomes. The recipients did not have a prior history of COVID-19, nor did they receive monoclonal antibodies post-transplantation; one was unvaccinated. If the safety and long-term outcomes from SARS-CoV-2 LRT NAT positive donors are confirmed in larger studies, this strategy represents a promising way to increase the pool for organ donation.
Background: Few options are available for cytomegalovirus (CMV) treatment in transplant recipients resistant, refractory, or intolerant to approved agents. Letermovir (LET) is approved for prophylaxis in hematopoietic cell transplant (HCT) recipients, but little is known about efficacy in CMV infection. We conducted an observational study to determine the patterns of use and outcome of LET treatment of CMV infection in transplant recipients.Methods: Patients who received LET for treatment of CMV infection were identified at 13 transplant centers. Demographic and outcome data were collected.Results: Twenty-seven solid organ and 21 HCT recipients (one dual) from 13 medical centers were included. Forty-five of 47 (94%) were treated with other agents prior to LET, and 57% had a history of prior CMV disease. Seventy-seven percent were intolerant to other antivirals; 32% were started on LET because of resistance concerns. Among 37 patients with viral load < 1000 international units (IU)/ml at LET initiation, two experienced >1 log rise in viral load by week 12, and no deaths were attributed to
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