A 48-year-old man had erythema without warmth over his right ankle and dorsomedial foot, with nontender, nonpalpable purpura over the foot dorsum and scattered petechiae over the right lower leg 6 weeks after immobilization for an ankle fracture; temperature was 38.2°C (100.8°F) and the erythema faded when he elevated his leg above heart level. What is the diagnosis and what would you do next?
Background BK viremia in renal transplant recipients increases risk of BK virus-associated nephropathy (BKVAN), posing a threat to allograft function. Up to 30% of all renal transplant recipients develop BK viremia and 1-10% will develop BKVAN. With no effective antiviral, the mainstay of therapy to prevent BKVAN is immunosuppression reduction (IR). Case series showed potential efficacy of using intravenous immunoglobulins (IVIG) to treat BK viremia. However, a randomized placebo-controlled study is needed. Methods A multicenter prospective double-blinded randomized placebo-controlled proof-of-concept study was conducted at three transplant institutions. 14 adult renal transplant recipients diagnosed with BK viremia were randomized (1:1) to receive IVIG and IR versus placebo and IR and were followed for 12 months, with the primary endpoint defined as resolution of BK viremia by month 3. Samples were collected at 1, 2, 3, 6, and 12 months for viral load quantification and immunological assays. Results At enrollment, clinical characteristics of the IVIG group (n = 5) were similar to the control group (n = 9), except that a larger number of participants in the control group had delayed graft function (0% vs. 77.8%, p = 0.02) and a higher baseline BK viral load (11300 vs 99300 copies/mL, p = 0.04). At 3 months, 2 out of 5 patients in the treatment group and 4 out of 9 patients in the control group cleared their viremia (40% vs 44.4%, RR 0.89, 95% CI 0.21 – 3.35, p > 0.99). Patients who received IVIG and IR had reduction in viral load at 6 months only (11300 vs 141 copies/mL, p = 0.008). Those who received IR alone had continued reduction in viral load starting at 2 months (99300 vs 4700, 1542, 906, 278 copies/mL; p < 0.05). No participant progressed to BKVAN. Immunological profiles of each participant will be correlated to the viral load. Serum BK viral loads were higher in the placebo group than the IVIG group at enrollment, but not significantly different between the two groups at any of the follow-up time points. The dotted line represents threshold of viremia clearance at less than 1000 copies/mL. * p = 0.04. Bar – median (Mann-Whitney between group comparisons). Median serum BK viral loads of the IVIG group decreased at the 6 months follow-up time point. The dotted line represents threshold of viremia clearance at less than 1000 copies/mL. ** p = 0.008 (Mann-Whitney comparing enrollment to each follow-up time point). Median serum BK viral loads of the placebo group continued to decrease at each follow-up time point. The dotted line represents threshold of viremia clearance at less than 1000 copies/mL. * p = 0.04; ** p = 0.006; *** p = 0.0008, 0.0003 (Mann-Whitney comparing enrollment to each follow-up time point). Conclusion This proof-of-concept study illustrates that a clinical trial of IVIG versus placebo for the treatment of BK viremia in renal transplant recipients is feasible. IVIG may not be more effective than IR alone; its immunosuppressive effect may even limit BK clearance. A larger sample is needed to attenuate baseline differences between groups and to provide a higher level of evidence on IVIG therapy in BK viremia. Disclosures All Authors: No reported disclosures.
Background Bloodstream infections (BSIs) account for 18% of bacterial infections in the first year after solid organ transplantation (SOT). Enterococcus is an important cause of nosocomial BSI, accounting for up to 20% of BSIs in this population, with Vancomycin-resistant enterococcus (VRE) posing a particular risk. This study aims to characterize the epidemiology and outcomes of enterococcal BSIs in abdominal SOTs. Methods A retrospective, single-center, case-control study of adult abdominal organ transplant (kidney transplant (KT), liver transplant (LT), simultaneous liver-kidney transplant (SLK), pancreas transplant, or simultaneous pancreas-kidney transplant) recipients between 01/01/2016 - 07/30/2021 was conducted at Beth Israel Deaconess Medical Center. Subjects were identified and reviewed using the Organ Transplant Tracking Record, their online medical record, and Vigilanz. Subjects with an enterococcal BSI within the first 6 months post-transplant were compared to those with non-enterococcal BSIs in the same period. Results We identified 26 subjects with enterococcal BSIs and 28 controls with non-enterococcal BSIs (n = 54; 10.2%). Cases were mostly LT recipients (n = 20; 77%) with a median MELD at transplant of 33 (range 14 - 43). Controls included 8 LT recipients (29%), 14 KT recipients (50%), and 6 SLK recipients (21.4%). Groups differed significantly (all p< 0.05) by factors including perioperative transfusion requirements, need for reoperation, and number of interventions post-transplant. Most cases (n = 16; 62%) and 11 controls (39%) had received antibiotics within the month prior to transplant. Cases had a median time of 25.5 days to infection and controls 100.5 days (p < 0.0001) (Figure 1). There were no differences in 1-year mortality (Figure 2) between the groups. E. faecium was the predominant species of Enterococcus (n = 23; 88.5%), with a majority (91.3%) of the isolates being VRE. The VRE rate was 80.8% among cases, 38.9% among all BSIs, and 4.0% among all transplants. Table 1:Demographic, Surgical, Hospitalization, and Antimicrobial Data. Baseline demographic and clinical characteristics of enterococcal BSI cases and non-enterococcal BSI controls are compared, along with transplant characteristics, transfusion requirements, surgical risk factors, hospitalization data, outcomes, and antibiotic exposures. Microbiological and resistance data are also presented. Enterococcal BSIs had lower odds of being a kidney transplant and having CKD or CKD on RRT; they had higher odds of being a liver transplant and having prior immunosuppression, steroid induction alone, reoperations, and macrolide exposure. Enterococcal BSIs had lower KDPIs, higher transfusion requirements, lower cold ischemia times, more procedures, and a shorter time to BSI (Chi-square and Fischer exact tests for categorical variables; Mann-Whitney tests for continuous variables). **Liver and simultaneous liver-kidney transplants; ***Kidney and simultaneous liver-kidney transplants; ****Reoperation within two weeks of primary closure; *****Biopsy proven acute antibody or cellular rejection within 6 months of transplant; ******ERCP stenting compared to IR stenting, among those with biliary complication. BSI – bloodstream infection; CKD – chronic kidney disease; HIV – human immunodeficiency virus; MELD – model of end stage liver disease; KDPI – kidney donor profile index; CMV – cytomegalovirus; pRBC – packed red blood cells; ERCP – endoscopic retrograde cholangiopancreatography; RRT – renal replacement therapy. Figure 1:Time to Bloodstream InfectionProbability of BSI-free survival illustrated, with enterococcal BSIs occurring significantly earlier than non-enterococcal BSIs post-transplantation (Kaplan-Meier survival analysis). BSI – bloodstream infection.Figure 2:MortalityProbability of survival, without significant difference between enterococcal and non-enterococcal BSIs. Data censored at one year of follow-up. BSI – bloodstream infection. Conclusion In our abdominal organ SOTs, enterococcal BSIs occurred early among LT recipients. The high incidence of VRE among E. faecium isolates in this population warrants further investigation into the optimal approach to empiric antimicrobials for bacteremia in the early post-transplant period. Disclosures Carolyn D. Alonso, MD, Cidara Therapeutics: Advisor/Consultant|Merck: Advisor/Consultant.
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