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Background: Cell‐free next‐generation sequencing (cfNGS) may have a unique role in the diagnosis of infectious complications in immunocompromised hosts. The rapid turnaround time and non‐invasive nature make it a promising supplement to standard of care. Methods: This retrospective, observational single‐center study at a tertiary care medical center in Virginia investigated the use of cfNGS in clinical practice. Patients over age 18 years with cfNGS performed for any indication were included. The primary outcome was detection of bacteria and/or fungi on cfNGS. The secondary outcomes were concordance, and abundance of fungal and bacterial organism concentration detected over time from symptom onset, and clinical impact. Results: Thirty‐six patients (92% immunosuppressed) were identified and included. Twenty‐one (58%) tests detected one to five organisms (14/21 bacteria, 8/21 fungi, and 6/21 viruses). The clinical impact of cfNGS was positive in 52.8% of cases, negative in 2.8%, and negligible in 44.4%. Positive tests prompted therapy changes in 12 of 21 patients; six of 20 bacteria and seven of eight fungi identified were considered clinically pathogenic. Three bacteria identifications and six fungi identifications prompted targeted treatment. When fungal species were not identified by cNFGS, antifungal de‐escalation occurred in seven patients. Conclusion: cfNGS assisted in critical management changes, including initiation of treatment for identified organisms and antimicrobial de‐escalation. Its non‐invasive nature and rapid turnaround time make this an important adjunct to standard of care testing that may assist in providing earlier, targeted therapy, especially when opportunistic pathogens remain high on the differential diagnosis. [ABSTRACT FROM AUTHOR]

The viral load in a patient's SARS-CoV-2 PCR test can be approximately quantified using the cycle threshold (Ct) value. Although this patient was at a higher risk given recent active infection with low Ct and ongoing disease present, he successfully underwent DDLT given his high risk for mortality due to cirrhosis. For patients with lower Ct values or recent active disease, preoperative monoclonal antibody and perioperative remdesivir may assist in reducing risk for COVID-19 progression in the early posttransplant setting although more studies are needed to determine this. [Extracted from the article]

Triazole antifungal drugs may rarely cause serious allergic reactions including angioedema. No standardized tests are available to predict cross-reactivity within the azole class and little guiding information exists on whether to change therapy within the class or to another class after a serious allergic reaction. Herein we report the first successful use, to our knowledge, of graded isavuconazole introduction for treatment of aspergillosis in a liver transplant recipient with severe voriconazole allergy. [ABSTRACT FROM AUTHOR]

Background Transplant infectious diseases (TID) is a growing area of expertise within infectious diseases (ID), but TID training is not standardized. Previous surveys of fellows identified opportunities to improve TID education resources but did not explore didactic, clinical, and nonclinical experiences comprehensively. Methods The American Society of Transplantation ID Community of Practice surveyed adult and pediatric fellows in US-based general ID or dedicated TID training programs to explore their didactic exposure, clinical experiences, and non–direct patient care activities in TID. Results A total of 234 fellows initiated the survey, and 195 (83%) (190 general ID and 19 TID fellows, including 125 adult, 76 pediatric, and 8 combined adult-pediatric fellows) completed the entire survey. More than half of the fellows described receiving no formal curricular content on most foundational topics in transplant medicine. Almost all respondents (>90%) had some inpatient TID experience, but for >60% of fellows this was <12 weeks annually. Clinical exposure varied by fellow and patient type—in an average month rotating on an inpatient TID service, more than half of adult fellows had evaluated ≥10 kidney, liver, or hematopoietic stem cell transplant recipients but <10 heart, lung, pancreas, or intestinal recipients; pediatric fellows saw <10 of all patient types. Nearly half (46%) of general ID fellows had not spent any time in the dedicated TID clinic at their program. Few fellows had participated in protocol development, organ selection meetings, or donor evaluations. Conclusions This survey highlights important gaps in TID training. Given the increasing need for TID specialists, updated curricula and educational resources are needed. [ABSTRACT FROM AUTHOR]

Background: Post‐COVID‐19 cholangiopathy is an emerging cholestatic liver disease observed in patients recovering from severe COVID‐19 infection. Its prognosis is poor, necessitating liver transplantation in some cases. This study aimed to investigate the outcomes of liver transplantation for post‐COVID‐19 cholangiopathy. Methods: Seven patients who underwent liver transplantation for post‐COVID‐19 cholangiopathy at three institutions between 2020 and 2022 were included in this retrospective multi‐center case series. Results: At the time of initial COVID‐19 infection, all patients developed acute respiratory distress syndrome, and six patients (86%) required ICU admission. Median time intervals from the initial COVID‐19 diagnosis to the diagnosis of post‐COVID‐19 cholangiopathy and liver transplantation were 4 and 12 months, respectively. Four patients underwent living donor liver transplantation, and three patients underwent deceased donor liver transplantation. The median MELD score was 22 (range, 10–38). No significant intraoperative complications were observed. The median ICU and hospital stays were 2.5 and 12.5 days, respectively. One patient died due to respiratory failure 5 months after liver transplantation. Currently, the patient and graft survival rate is 86% at a median follow‐up of 11 months. Conclusions: Liver transplantation is a viable option for patients with post‐COVID‐19 cholangiopathy with acceptable outcome. Timely identification of this disease and appropriate management, including evaluation for liver transplantation, are essential. [ABSTRACT FROM AUTHOR]

Nocardia species represent a well‐recognized yet uncommon cause of opportunistic infections in humans. It most frequently presents as a pulmonary infection with or without central nervous system involvement. It is a very rare cause of spinal abscesses, with only 26 cases reported in the literature. Here we report a 49‐year‐old man with a history of renal transplantation who presented with low back pain and was diagnosed with epidural and paraspinal abscesses due to Nocardia cyriacigeorgica that was successfully treated with antimicrobial therapy alone. In addition to the case reported here, we also conducted a systematic review of the existing literature regarding spinal abscesses due to Nocardia species and examined the success of the various treatments utilized. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a disorder of immune regulation, manifested by fever, pancytopenia, hyperferritiniemia, hypertriglyceridemia, and extensive hemophagocytosis involving the bone marrow and spleen. HLH can occur in adults with an underlying hematopoietic malignancy, or with systemic infections. HLH following hematopoietic stem cell transplantation (HSCT) is unusual, and the diagnosis may be challenging particularly because the diagnostic criteria in the HLH‐2004 guidelines overlap with common post‐transplant complications such as engraftment syndrome, graft‐vs‐host disease, and infections. HLH is commonly triggered by viral, bacterial and, less commonly, parasitic infections. Following HSCT, patients with latent Toxoplasma infection may develop systemic disease secondary to reactivation, and rarely this may lead to a HLH physiology, with a very high mortality rate. Herein we describe the successful management of disseminated toxoplasmosis associated with life‐threatening HLH using tocilizumab and antimicrobial therapy. [ABSTRACT FROM AUTHOR]

Background: Reports that septic shock incidence is rising and mortality rates declining may be confounded by improving recognition of sepsis and changing coding practices. We compared trends in septic shock incidence and mortality in academic hospitals using clinical vs claims data.Methods: We identified all patients with concurrent blood cultures, antibiotics, and vasopressors for ≥ two consecutive days, and all patients with International Classification of Diseases, 9th edition (ICD-9) codes for septic shock, at 27 academic hospitals from 2005 to 2014. We compared annual incidence and mortality trends. We reviewed 967 records from three hospitals to estimate the accuracy of each method.Results: Of 6.5 million adult hospitalizations, 99,312 (1.5%) were flagged by clinical criteria, 82,350 (1.3%) by ICD-9 codes, and 44,651 (0.7%) by both. Sensitivity for clinical criteria was higher than claims (74.8% vs 48.3%; P < .01), whereas positive predictive value was comparable (83% vs 89%; P = .23). Septic shock incidence, based on clinical criteria, rose from 12.8 to 18.6 cases per 1,000 hospitalizations (average, 4.9% increase/y; 95% CI, 4.0%-5.9%), while mortality declined from 54.9% to 50.7% (average, 0.6% decline/y; 95% CI, 0.4%-0.8%). In contrast, septic shock incidence, based on ICD-9 codes, increased from 6.7 to 19.3 per 1,000 hospitalizations (19.8% increase/y; 95% CI, 16.6%-20.9%), while mortality decreased from 48.3% to 39.3% (1.2% decline/y; 95% CI, 0.9%-1.6%).Conclusions: A clinical surveillance definition based on concurrent vasopressors, blood cultures, and antibiotics accurately identifies septic shock hospitalizations and suggests that the incidence of patients receiving treatment for septic shock has risen and mortality rates have fallen, but less dramatically than estimated on the basis of ICD-9 codes. [ABSTRACT FROM AUTHOR]

Background Invasive fungal infections (IFI) are life-threatening complications of prolonged neutropenia in hematologic cancer or after hematopoietic stem cell transplantation (HSCT). Guidelines recommend mold prophylaxis (ppx) for patients at high risk of IFI. Patients receiving ppx with new signs of infection are often escalated to Liposomal Amphotericin B (L-AmB) for concerns of breakthrough mold infections. We describe the impact of implementing voriconazole (VZL) ppx in cancer patients. Methods We performed a quasi-experimental study of all adult patients prescribed L-AmB for ≥1 dose in Cancer Center at the University of Maryland Medical Center. VZL ppx was implemented for patients with hematologic cancer with anticipated prolonged neutropenia (≥ 7 days) in 4/2017. HSCT patients routinely received posaconazole ppx for ≥ 1 year during study period. Comparisons were made pre (November 2015–June 2017) and post (July 2017–December 2018) implementation of VZL ppx allowing for 3-month wash-in period. Cancer center-specific L-AmB days of therapy (DOT) per 1,000 patient-days (PD) were compared using segmented regression and Student t -test. Comparison of patient characteristics, mortality, nephrotoxicity and hospital length of stay (LOS) among patients receiving L-AmB in pre vs. post periods was done using Χ 2 and Student t -test. Results There were 87 (24 pre, 63 post) unique patients included in the analysis, translating to a total of 17.6 L-AmB DOT per 1,000 PD for the study period. Mean L-AmB utilization in cancer center was 9.9 and 24.4 DOT per 1,000 PD (P = 0.0037) for pre and post-implementation, respectively. There was an average 16% increase of L-Amb quarterly (P = 0.93). Among patients receiving L-AmB, most had acute myelogenous leukemia (63% vs. 60%) with lung source (71% vs. 73%, P = 0.8). More patients had proven IFI pre-implementation (42% vs. 29%, P = 0.3). Nephrotoxicity (46% vs. 48%, P = 0.9), median LOS (17 vs. 28, P = 0.4) and inpatient mortality (30 % vs. 38%, p = 0.5) all increased without statistical significance. Conclusion After implementation of VZL ppx there was a significant increase in L-AmB use, and associated non-significant increases in LOS, mortality and nephrotoxicity for those receiving L-AmB. Larger, robust longitudinal studies are needed to better understand the implications of VZL ppx on this population. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]