Background Patients with reported beta lactam antibiotic allergies (BLA) are more likely to receive broad-spectrum antibiotics and experience adverse outcomes. Data describing antibiotic allergies among solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients are limited. Methods We reviewed records of adult SOT or allogeneic HCT recipients from 1/1/2013-12/31/2017 to characterize reported antibiotic allergies at time of transplant. Inpatient antibiotic use was examined for 100 days post-transplant. Incidence rate ratios (IRR) comparing antibiotic use in BLA and non-BLA groups were calculated using multivariable negative binomial models for two metrics: days of therapy (DOT)/1000 inpatient days and percentage of antibiotic exposure days. Results Among 2153 SOT (65%) and HCT (35%) recipients, 634 (29%) reported any antibiotic allergy and 347 (16%) reported BLA. Inpatient antibiotics were administered to 2020 (94%) patients during the first 100 days post-transplant; average antibiotic exposure was 41% of inpatient days (Interquartile range (IQR) 16.7%, 62.5%). BLA patients had significantly higher DOT for vancomycin (IRR 1.4; 95% confidence interval (CI) [1.2, 1.7]; p<0.001), clindamycin (IRR 7.6; 95% CI [2.2, 32.4]; p=0.001), aztreonam in HCT (IRR 9.7; 95% CI [3.3, 35.0]; p<0.001), and fluoroquinolones in SOT (IRR 2.9; 95% CI [2.1, 4.0]; p<0.001); these findings were consistent when using percentage of antibiotic exposure days. Conclusions Transplant recipients are frequently exposed to antibiotics and have a high prevalence of reported antibiotic allergies. Reported BLA was associated with greater use of beta lactam antibiotic alternatives. Pre-transplant antibiotic allergy evaluation may optimize antibiotic use in this population.

BK polyomavirus (BKPyV) has been associated with hemorrhagic cystitis (HC) after allogeneic hematopoietic cell transplantation (HCT), but the natural history of HC and factors associated with the clinical course are incompletely understood. We retrospectively analyzed allogeneic HCT patients transplanted from 2007-2017 who presented after platelet engraftment or after day 28 post-HCT with BKPyV-associated HC (BKPyV-HC), which was defined as a positive urine BKPyV PCR, ≥1 plasma BKPyV viral load result, and macroscopic hematuria (Bedi grade ≥2). Factors associated with resolution of macroscopic hematuria and resolution of all cystitis symptoms within 90 days after HC diagnosis were investigated in multivariable models. In 128 patients with BKPyV-HC, the median times from diagnosis to resolution of all symptoms, macroscopic hematuria, and urinary clots (present in 55% [71/128]) were 24 days (15-44), 17 days (10-30), and 14 days (5-26), respectively. Ninety percent of patients had BKPyV viremia at the onset of HC with a median viral load of 1850 copies/mL (interquartile range, 240-8550). In multivariable models, high plasma viral load (≥10 000 copies/mL) and cytopenias at the beginning of BKPyV-HC were significantly associated with longer macroscopic hematuria and cystitis symptoms. Use of cidofovir was not associated with shorter duration of illness. In conclusion, BKPyV-HC after allogeneic HCT is characterized by prolonged and severe symptoms and requires improved management strategies. High-grade viremia and cytopenias were associated with a longer duration of BKPyV-associated HC. Accurate descriptions of disease and factors associated with prolonged recovery will inform end points of future clinical trials.

To expand the available donor pool, many organ procurement organizations and transplant programs have begun to consider severe acute respiratory syndrome coronavirus (SARS-CoV-2) nucleic acid test positive candidates. 1 It is becoming increasingly clear that not all donors with a positive nucleic acid amplification test for SARS-CoV-2 are contagious, and some of these organs can be transplanted with careful selection. 2,3 Data from 31 kidney transplants from living donors with resolved COVID-19 in India showed the safety of this approach. 4 However, it is unknown whether kidneys from donors with active COVID-19 can also be safely transplanted. 3,5 Beyond the "active" infection designation, it is clinically possible to risk stratify donors with COVID-19 based on additional parameters such as clinical history and radiologic or laboratory findings. Here we present a case and 210-day outcome of a successful kidney transplantation from otherwise medically suitable SARS-CoV-2 PCR-positive deceased donors.

Until recently, available drugs for cytomegalovirus (CMV) prevention and treatment in transplant patients included (val)ganciclovir, foscarnet, and cidofovir. Use of these drugs is limited by toxicity and the development of resistance. The 2017 approval of letermovir for prevention of CMV after stem cell transplant marked the first approval of an anti-CMV agent since 2003. The role of letermovir in treatment of established CMV infection or disease remains largely unstudied, although early reports suggest that a low barrier to resistance will likely limit efficacy as primary therapy for patients with refractory or resistant disease. The investigational agent maribavir has shown promise as pre-emptive treatment; in patients with refractory or resistant disease the emergence of resistance while on treatment has been observed and ongoing studies will define efficacy in this population. Both agents have unique mechanisms of action limiting cross resistance, and neither exhibit myelotoxicity or nephrotoxicity.

Cytomegalovirus (CMV) reactivation has been described in adults with critical illness caused by diverse etiologies, especially severe sepsis, and observational studies have linked CMV reactivation with worse clinical outcomes in this setting. In this study, we review observational clinical data linking development of CMV reactivation with worse outcomes in patients in the intensive care unit, discuss potential biologically plausible mechanisms for a causal association, and summarize results of initial interventional trials that examined the effects of CMV prevention. These data, taken together, highlight the need for a randomized, placebo-controlled efficacy trial (1) to definitively determine whether prevention of CMV reactivation improves clinical outcomes of patients with critical illness and (2) to define the underlying mechanism(s).

Introduction BK Polyomavirus (BKPyV) infection and BK Polyomavirus nephropathy (BKPyVAN) are important causes of allograft dysfunction and premature allograft loss in renal transplant recipients. Results and Discussion Controlled clinical trials to evaluate new agents for prevention and treatment are needed but are hampered by the lack of outcome measures that accurately assess the effect of the intervention, are clinically-relevant, and are acceptable from a regulatory perspective. To facilitate consistent endpoints in clinical trials and to support clinical research and drug development, definitions of BKPyV infection and disease have been developed by the BK Disease Definitions Working group of the Transplantation Associated Virus Infection Forum with the Forum for Collaborative Research, which consists of scientists, clinicians, regulators, and industry representatives. Conclusion These definitions refine established principles of “proven” BKPyV disease and introduce a “probable” disease category that could be used in clinical trials to prevent or treat BKPyVAN in renal transplant recipients.

A significant proportion of BKPyVAN is late-onset, especially among SPK recipients, and supports a longer duration of BKPyV monitoring for SPK recipients than recommended in some guidelines.

Among solid organ transplant recipients, donor cytomegalovirus (CMV) seropositive (D+) and recipient seronegative (R−) status are associated with an increased risk of graft loss and mortality after kidney or lung transplantation. Whether a similar relationship exists among liver transplant recipients (LTR) is unknown. We assessed graft loss and mortality among adult LTRs from January 1, 2010, to March 14, 2020, in the Organ Procurement and Transplantation Network database. We used multivariable mixed Cox proportional hazards regression to analyze the association of donor and recipient CMV serostatus group with graft loss and mortality, with donor seronegative (D−) and recipient seronegative (R−) as the reference group. Among 54,078 LTRs, the proportion of D−R−, D− and recipient seropositive (R+), D+R−, and D+R+ was 13.4%, 22.5%, 22%, and 42%, respectively. By unadjusted Kaplan-Meier survival curve estimates, survival by the end of follow-up was 73.3%, 73.5%, 70.1%, and 69.7%, among the D−R−, D−R+, D+R−, and D+R+ groups, respectively. By multivariable Cox regression, the CMV D+R− serogroup, but not other serogroups, was independently associated with increased risks of graft loss (adjusted hazard ratio [aHR], 1.13; 95% confidence interval [CI], 1.05-1.22) and mortality (aHR, 1.13; 95% CI, 1.05-1.22). The magnitude of the association of the CMV D+R− serostatus group with mortality was similar when the Cox regression analysis was restricted to the first year after transplant and beyond the first year after transplant: aHR, 1.13 (95% CI, 1.01-1.27) and aHR, 1.13 (95% CI, 1.02-1.25), respectively. Even in an era of CMV preventive strategies, CMV D+R− serogroup status remains independently associated with increased graft loss and mortality in adult LTRs. Factors in addition to direct CMV-associated short-term mortality are likely, and studies to define the underlying mechanism(s) are warranted.