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Transplant-related hepatitis E virus (HEV) infection is a rarely recognized phenomenon with significant clinical importance given its potential to result in chronic hepatitis posttransplant.We retrospectively evaluated HEV diagnosis and treatment after liver, kidney, and heart transplant in a single center. We identified patients diagnosed with HEV by serologic testing and evaluated their treatment regimens.Fifteen transplant recipients (12 liver, 2 kidney, and 1 heart) presented with elevated liver enzymes and were positive for HEV IgM antibody. Liver enzymes normalized in 4 patients after being treated with ribavirin. One of the 4 patients had 2 recurrences with positive HEV RNA results following ribavirin treatment but recovered after 12 months of ribavirin therapy. After treatment with reduction in immunosuppression without antiviral treatment, 6 of 8 patients' liver enzymes normalized. One of these patients died of acute pancreatitis 2 months after testing positive for HEV IgM antibody.The potential for complications related to active HEV infections in transplant recipients necessitates prompt diagnosis and treatment to prevent irreversible damage. Diagnosis with HEV reverse transcriptase-polymerase chain reaction should follow a positive HEV IgM antibody test. This manuscript provides evidence that ribavirin antiviral therapy and reducing immunosuppression are effective treatments for HEV infections in liver, kidney, and heart transplant recipients, which has not been sufficiently investigated in the population of the United States. Larger multicenter studies are needed to confirm the risks and benefits of using ribavirin antiviral therapy as first-line therapy of HEV posttransplant.

There is an increased risk of potential drug–drug interactions (pDDIs) in critically ill patients based on the number of drugs received. The occurrence of pDDIs and clinical significance is not well described. The aim was to provide insight into important clinical issues and offer guidance on drug–drug interaction (DDI) surveillance through the performance of a systematic review. Five targeted objectives were developed, a priori, which guided study selection and data abstraction. Two independent reviewers extracted the definition, frequency, type, and clinical significance of pDDIs. A meta-analysis was performed to evaluate the proportion of patients exposed to a pDDI. Three data sources (PubMed, Embase, and Scopus) were utilized for the search to include studies that evaluated pDDIs in adult critically ill patients. Included studies in the systematic review and meta-analysis were required to be full text. A total of 39 studies met inclusion criteria. Definitions of pDDIs were diverse. Frequency of pDDIs varied by study, but was most commonly between one and five pDDIs per patient. Fifty-eight percent of patients were exposed to at least one pDDI during their intensive care unit admission. Types of pDDIs identified were numerous, with aspirin being the most common drug involved. As expected, not all pDDIs were clinically significant. Clinical significance was determined by varied definitions and sources. Improving the understanding of clinically significant pDDIs and alerts that clinicians encounter may guide better development of surveillance through clinical decision support and decrease alert fatigue.

Anti-factor Xa (anti-Xa) monitoring of unfractionated heparin (UFH) is associated with less time to achieve therapeutic anticoagulation compared to the activated partial thromboplastin time (aPTT). However, it is unknown whether clinical outcomes differ between these methods of monitoring. The aim of this research was to compare the rate of venous thrombosis and bleeding events in patients that received UFH monitored by anti-Xa compared to the aPTT. A retrospective review of electronic health records identified adult patients that received UFH given intravenously (IV) for ≥2 days, with either anti-Xa or aPTT monitoring at an academic tertiary care hospital. This was a pre/post study design conducted between January 1 to December 30, 2014 (aPTT), and January 1 to December 30, 2016 (anti-Xa). All UFH adjustments were based on institutional nomograms. The primary outcome was venous thrombosis and the secondary outcome was bleeding, both of which occurred between UFH administration and discharge from the index hospitalization. A total of 2500 patients were in the anti-Xa group and 2847 patients aPTT group. Venous thrombosis occurred in 10.2% vs 10.8% of patients in the anti-Xa and aPTT groups, respectively (P = .49). Bleeding occurred in 33.7% vs 33.6% of patients in the anti-Xa and aPTT groups, respectively (P = .94). Anti-Xa monitoring was not an independent predictor of either outcome in multivariate logistic regression analyses. Our study found no difference in clinical outcomes between anti-Xa and aPTT-based monitoring of UFH IV.

Background Standard dose ganciclovir (SD-GCV) for treatment of CMV infection/disease is 5 mg/kg every 12 hours, although higher doses (7.5–10 mg/kg every 12 hours) may be considered for resistant CMV. Literature on safety/efficacy of high dose GCV (HD-GCV) is limited. We sought to evaluate safety and clinical outcomes of SD-GCV vs HD-GCV strategies. Methods Retrospective single center study of adult SOT recipients with CMV viremia from 1/1/2017-1/31/2019 who received IV GCV therapy. Primary objective was to compare incidence of cytopenias between SD-GCV and HD-GCV. Secondary outcomes compared CMV viremia clearance, incidence of CMV disease and recurrent viremia within 30 days, granulocyte colony stimulating factor (G-CSF) use, and antiviral resistance testing rates. Results We evaluated 121 patients: 74 received SD-GCV, 47 received HD-GCV. Baseline characteristics were similar between groups. Most patients received a liver transplant (46% SD vs 36% HD) and had D+/R- CMV serostatus (55.4% SD vs 68% HD). Induction immunosuppression occurred in 75%, mostly with anti-thymocyte globulin. Median baseline CMV viral loads were similar (4620 IU/mL SD vs 7770 IU/mL HD, p=0.25). Incidence of cytopenias was similar between groups: leukopenia (43% SD vs 43% HD, p=0.96), neutropenia (15% SD vs 13% HD, p= 0.75), thrombocytopenia (24% SD vs 31% HD, p=0.62). HD-GCV did not significantly impact CMV clearance (HR: 0.79 [95% CI 0.52–1.21], p=0.27). There was no difference in incidence of CMV disease (35% SD vs 38% HD, p=0.72) or incidence of recurrent CMV viremia (15% SD vs 28% HD, p=0.098). G-CSF requirement was not different (23.7% SD vs 14.3% HD, p=0.295), however, patients on HD-GCV received more doses of G-CSF (median 2 SD vs 5 HD, p=0.001). More patients in HD-GCV group were tested for antiviral resistance: 15 (21%) SD vs 20 (43%) HD, p=0.01. Of these, there was no difference in rate of resistance detection (7/15 (47%) SD vs 11/20 (55%) HD, p=0.95). Conclusion Therapy with HD-GCV did not demonstrate increased incidence of cytopenias compared to SD-GCV, nor did we observe improved time to CMV clearance or incidence of CMV disease between groups. Opportunities exist for improving stewardship of antiviral resistance testing and use of G-CSF when considering HD-GCV therapy. Disclosures All Authors: No reported disclosures