Hepatitis B transmission/reactivation associated with Hepatitis B core antibody and Hepatitis C nucleic acid testing positive organs: A report from the Organ Procurement and Transplantation Network Disease Transmission Advisory Committee.

BACKGROUND: Better access to direct-acting antiviral (DAA) therapy has broadened the utilization of hepatitis C virus (HCV) nucleic acid testing (NAT) positive organs with excellent outcomes. However, DAA therapy has been associated with hepatitis B virus (HBV) reactivation. AIM: To determine the risk of HBV transmission or reactivation with utilization of HBV core antibody positive (HBcAb+) and HCV NAT positive (HCV+) organs, which presumably required DAA therapy. METHODS: The number of HBcAb+ donors with delineated HCV NAT status was obtained from the Organ Procurement and Transplantation Network (OPTN) database. The number of unexpected HBV infections from transplanted organs adjudicated as "proven" or "probable" transmission was obtained from the OPTN Ad Hoc Disease Transmission Advisory Committee database. A chart review of the donors of "proven" or "probable" cases was conducted. RESULTS: From January 1, 2016, to December 31, 2021, 7735 organs were procured from 3767 HBcAb+ donors and transplanted into 7469 recipients; 545 (14.5%) donors were also HCV+. HBV transmission or reactivation occurred in seven recipients. The rate is not significantly different between recipients of HCV+ (0.18%, 2/1115) and the HCV NAT negative (HCV-) organs (0.08%, 5/6354) (p = 0.28) or between recipients of HCV+ and HCV- livers as well as non-liver organs. HBV transmission or reactivation occurred within a median of 319 (range, 41-1117) days post-transplant in the setting of missing, inadequate, or truncated prophylaxis. CONCLUSION: HBV reactivation associated with DAA therapy for HBcAb+ HCV+ organs is less frequent than reported in the non-transplant population, possibly due to the common use of HBV prophylaxis in the at-risk transplant population.

Trypanosoma cruzi Reactivation After Chimeric Antigen Receptor T-Cell Therapy.

https://tidbitapp.io/tidbits/trypanosoma-cruzi-reactivation-post-chimeric-antigen-receptor-t-cell-therapy/update.

18F-FDG PET/CT in left ventricular assist device infections: In-depth characterization and clinical implications.

BACKGROUND: Previous retrospective studies suggest a good diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)/computed tomography (CT) in left ventricular assist device (LVAD) infections. Our aim was to prospectively evaluate the role of PET/CT in the characterization and impact on clinical management of LVAD infections. METHODS: A total of 40 patients (aged 58 [53-62] years) with suspected LVAD infection and 5 controls (aged 69 [64-71] years) underwent 18F-FDG-PET/CT. Four LVAD components were evaluated: exit site and subcutaneous driveline (peripheral), pump pocket, and outflow graft. The location with maximal uptake was considered the presumed site of infection. Infection was confirmed by positive culture (exit site or blood) and/or surgical findings. RESULTS: Visual uptake was present in 40 patients (100%) in the infection group vs 4 (80%) control subjects. For each individual component, the presence of uptake was more frequent in the infection than in the control group. The location of maximal uptake was most frequently the pump pocket (48%) in the infection group and the peripheral components (75%) in the control group. Maximum standard uptake values (SUVmax) were higher in the infection than in the control group: SUVmax (average all components): 6.9 (5.1-8.5) vs 3.8 (3.7-4.3), p = 0.002; SUVmax (location of maximal uptake): 10.6 ± 4.0 vs 5.4 ± 1.9, p = 0.01. Pump pocket infections were more frequent in patients with bacteremia than without bacteremia (79% vs 31%, p = 0.011). Pseudomonas (32%) and methicillin-susceptible Staphylococcus aureus (29%) were the most frequent pathogens and were associated with pump pocket infections, while Staphylococcus epidermis (11%) was associated with peripheral infections. PET/CT affected the clinical management of 83% of patients with infection, resulting in surgical debridement (8%), pump exchange (13%), and upgrade in the transplant listing status (10%), leading to 8% of urgent transplants. CONCLUSIONS: 18F-FDG-PET/CT enables the diagnosis and characterization of the extent of LVAD infections, which can significantly affect the clinical management of these patients.

Eradicating Pulmonary Mycobacterium abscessus: The Promise of Dual ß-Lactam Therapy.

Macrolide resistance has rendered the treatment of Mycobacterium abscessus extremely difficult and is fueling a crisis. Recently, there has been dramatically increased incidence of infections by M abscessus. Select dual ß-lactam combinations have shown promising in vitro results. Herein, we present a patient whose M abscessus infection cured using dual ß-lactams as part of multidrug regimen.

Transplant of organs from donors with positive SARS-CoV-2 nucleic acid testing: A report from the organ procurement and transplantation network ad hoc disease transmission advisory committee.

BACKGROUND: Decisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test-positive (NAT+) donors must balance risk of donor-derived transmission events (DDTE) with the scarcity of available organs. METHODS: Organ Procurement and Transplantation Network (OPTN) data were used to compare organ utilization and recipient outcomes between SARS-CoV-2 NAT+ and NAT- donors. NAT+ was defined by either a positive upper or lower respiratory tract (LRT) sample within 21 days of procurement. Potential DDTE were adjudicated by OPTN Disease Transmission Advisory Committee. RESULTS: From May 27, 2021 (date of OTPN policy for required LRT testing of lung donors) to January 31, 2022, organs were recovered from 617 NAT+ donors from all OPTN regions and 53 of 57 (93%) organ procurement organizations. NAT+ donors were younger and had higher organ quality scores for kidney and liver. Organ utilization was lower for NAT+ donors compared to NAT- donors. A total of 1241 organs (776 kidneys, 316 livers, 106 hearts, 22 lungs, and 21 other) were transplanted from 514 NAT+ donors compared to 21 946 organs from 8853 NAT- donors. Medical urgency was lower for recipients of NAT+ liver and heart transplants. The median waitlist time was longer for liver recipients of NAT+ donors. The match run sequence number for final acceptor was higher for NAT+ donors for all organ types. Outcomes for hospital length of stay, 30-day mortality, and 30-day graft loss were similar for all organ types. No SARS-CoV-2 DDTE occurred in this interval. CONCLUSIONS: Transplantation of SARS-CoV-2 NAT+ donor organs appears safe for short-term outcomes of death and graft loss and ameliorates the organ shortage. Further study is required to assure comparable longer term outcomes.

Duration of antibiotic treatment for acute graft pyelonephritis: What's the standard of care?

BACKGROUND: Limited evidence is available to inform the duration of antibiotic treatment in kidney transplant recipients with bacterial acute graft pyelonephritis. Guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation suggest a 14-21 day duration. METHODS: A four-question survey was constructed to determine the current standard of practice for the duration of treatment for acute graft pyelonephritis. The survey was distributed among members of the Infectious Diseases and the Kidney Pancreas Communities of Practice of the American Society of Transplantation. RESULTS: Among 144 survey respondents, 87 (60%) were infectious disease physicians, and 36 (25%) were transplant nephrologists. Although most (55%) respondents preferred a 14-day duration, a spread between 7 and 28 days was observed. Goals of treatment and drivers for longer duration differed between infectious disease physicians and transplant nephrologists. CONCLUSIONS: Although most respondents prefer a 14-day duration of treatment for acute graft pyelonephritis, a wide range of responses was seen between 7 and 28 days. More evidence is needed to inform optimal treatment duration in this common infectious complication after transplantation.

Candida auris Pan-Drug-Resistant to Four Classes of Antifungal Agents.

Candida auris is an urgent antimicrobial resistance threat due to its global emergence, high mortality, and persistent transmissions. Nearly half of C. auris clinical and surveillance cases in the United States are from the New York and New Jersey Metropolitan area. We performed genome, and drug-resistance analysis of C. auris isolates from a patient who underwent multi-visceral transplantation. Whole-genome comparisons of 19 isolates, collected over 72 days, revealed closed similarity (Average Nucleotide Identity > 0.9996; Aligned Percentage > 0.9764) and a distinct subcluster of NY C. auris South Asia Clade I. All isolates had azole-linked resistance in ERG11(K143R) and CDR1(V704L). Echinocandin resistance first appeared with FKS1(S639Y) mutation and then a unique FKS1(F635C) mutation. Flucytosine-resistant isolates had mutations in FCY1, FUR1, and ADE17. Two pan-drug-resistant C. auris isolates had uracil phosphoribosyltransferase deletion (FUR1[1Δ33]) and the elimination of FUR1 expression, confirmed by a qPCR test developed in this study. Besides ERG11 mutations, four amphotericin B-resistant isolates showed no distinct nonsynonymous variants suggesting unknown genetic elements driving the resistance. Pan-drug-resistant C. auris isolates were not susceptible to two-drug antifungal combinations tested by checkerboard, Etest, and time-kill methods. The fungal population pattern, discerned from SNP phylogenetic analysis, was consistent with in-hospital or inpatient evolution of C. auris isolates circulating locally and not indicative of a recent introduction from elsewhere. The emergence of pan-drug-resistance to four major classes of antifungals in C. auris is alarming. Patients at high risk for drug-resistant C. auris might require novel therapeutic strategies and targeted pre-and/or posttransplant surveillance.

Relation of Left Ventricular Assist Device Infections With Cardiac Transplant Outcomes.

Left ventricular assist device (LVAD)-specific infections (LSIs) are common in patients on LVAD support awaiting heart transplant (HT), yet their impact on post-HT outcomes is not completely understood. We hypothesized that LSIs would result in vasoplegia and negatively affect post-HT 30-day and 1-year outcomes. LSI was defined as driveline, pump, or pocket infection. The short-term outcome was a composite of acute renal failure, allograft rejection, and mortality at 30 days after HT. The long-term outcome was a composite of allograft rejection and death within 1 year after HT. We performed a retrospective analysis of 111 HT recipients bridged with durable LVAD support at our institution from May 2012 to August 2019. Of these, 63 patients had LSIs, with 94% of the infections being driveline infections. Vasoplegia was more prevalent in the LSI group but not significantly (7 vs 2 persons, p = 0.3). There was no difference in the composite end point of acute renal failure, rejection, or death at 30 days (30% vs 25%, p = 0.55) or 1-year end point of rejection and death (38% vs 40%, p = 0.87) in patients with LSI versus those without LSI. In conclusion, LSIs were common in patients on LVAD who underwent HT in our single-center contemporary cohort. However, LSI was not associated with adverse outcomes at 30 days or at 1 year after HT.

Relapsed Babesia microti Infection Following Allogeneic Hematopoietic Cell Transplantation in a Patient With B-cell Acute Lymphoblastic Leukemia: Case Report and Review of the Literature.

A patient with relapsed/refractory B-cell acute lymphoblastic leukemia developed babesiosis before allogeneic hematopoietic cell transplantation while on atovaquone for Pneumocystis jirovecii pneumonia prophylaxis. Despite receiving a prolonged course of atovaquone and azithromycin until whole-blood Babesia microti DNA was no longer detected by polymerase chain reaction, her post-transplant course was complicated by relapsed babesiosis. We investigate the potential host and parasite characteristics causing relapsing/persistent infection.

Impact of pre-transplant carbapenem-resistant Enterobacterales colonization and/or infection on solid organ transplant outcomes.

The impact of pre-transplant (SOT) carbapenem-resistant Enterobacterales (CRE) colonization or infection on post-SOT outcomes is unclear. We conducted a multi-center, international, cohort study of SOT recipients, with microbiologically diagnosed CRE colonization and/or infection pre-SOT. Sixty adult SOT recipients were included (liver n = 30, hearts n = 17). Klebsiella pneumoniae (n = 47, 78%) was the most common pre-SOT CRE species. Median time from CRE detection to SOT was 2.32 months (IQR 0.33-10.13). Post-SOT CRE infection occurred in 40% (n = 24/60), at a median of 9 days (IQR 7-17), and most commonly due to K pneumoniae (n = 20/24, 83%). Of those infected, 62% had a surgical site infection, and 46% had bloodstream infection. Patients with post-SOT CRE infection more commonly had a liver transplant (16, 67% vs. 14, 39%; p =.0350) or pre-SOT CRE BSI (11, 46% vs. 7, 19%; p =.03). One-year post-SOT survival was 77%, and those with post-SOT CRE infection had a 50% less chance of survival vs. uninfected (0.86, 95% CI, 0.76-0.97 vs. 0.34, 95% CI 0.08-1.0, p =.0204). Pre-SOT CRE infection or colonization is not an absolute contraindication to SOT and is more common among abdominal SOT recipients, those with pre-SOT CRE BSI, and those with early post-SOT medical and surgical complications.

Influence of patient characteristics and immunosuppressant management on mortality in kidney transplant recipients hospitalized with coronavirus disease 2019 (COVID-19).

The influence of patient characteristics and immunosuppression management on COVID-19 outcomes in kidney transplant recipients (KTRs) remains uncertain. We performed a single-center, retrospective review of all adult KTRs admitted to the hospital with confirmed COVID-19 between 03/15/2020 and 05/15/2020. Patients were followed from the date of admission up to 1 month following hospital discharge or study conclusion (06/15/2020). Baseline characteristics, laboratory parameters, and immunosuppression were compared between survivors and patients who died to identify predictors of mortality. 38 KTRs with a mean baseline eGFR of 52.5 ml/min/1.73 m2 were hospitalized during the review period. Maintenance immunosuppression included tacrolimus (84.2%), mycophenolate (89.5%), and corticosteroids (81.6%) in the majority of patients. Eleven patients (28.9%) died during the hospitalization. Older age (OR = 2.05; 1.04-4.04), peak D-dimer (OR = 1.20; 1.04-1.39), and peak white blood cell count (OR = 1.11; 1.02-1.21) were all associated with mortality among KTRs hospitalized for COVID-19. Increased mortality was also observed among KTRs with concomitant HIV infection (87.5% vs. 36.1%; p < .01). Conversely, immunosuppression intensity and degree of reduction following COVID-19 diagnosis were not associated with either survival or acute allograft rejection. Our findings potentially support a strategy of individualization of immunosuppression targets based on patient-specific risk factors, rather than universal immunosuppression reduction for KTRs at risk from COVID-19.

Treatment with convalescent plasma in solid organ transplant recipients with COVID-19: Experience at large transplant center in New York City.

Solid organ transplant (SOT) recipients may be at higher risk for poor outcomes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Convalescent plasma is an investigational therapy that may benefit immunosuppressed patients by providing passive immunity. Convalescent plasma was administered to hospitalized patients with coronavirus disease-2019 (COVID-19) at an academic transplant center in New York City. Eligible patients were hospitalized and required to have positive nasopharyngeal polymerase chain reaction (PCR) diagnosis of SARS-CoV-2 infection, be at least 18 years old, and have either dyspnea, blood oxygen saturation ≤ 93% on ambient air, respiratory frequency ≥ 30 breaths/min, partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300, or lung infiltrates > 50%. Thirteen SOT recipients received convalescent plasma from April 9, 2020, to May 17, 2020. The median time from symptom onset to plasma infusion was 8 days. Eight of 13 patients (62%) had de-escalating oxygenation support by day 7 post-convalescent plasma. Nine (69%) patients were discharged, 1 (7%) patients remain hospitalized, and 3 (23%) patients died. This series supports the need for additional studies on convalescent plasma use in SOT recipients with COVID-19 to better determine efficacy and identify patients who are likely to benefit.

Infections due to multidrug-resistant organisms following heart transplantation: Epidemiology, microbiology, and outcomes.

BACKGROUND: Infections secondary to multidrug-resistant organisms (MDRO) have emerged as a growing problem in solid organ transplantation (SOT). Most of the published data on MDRO infections in SOT pertains to abdominal organ transplantation and data specific to heart transplantation (HT) are limited. METHODS: This is a retrospective review of HT recipients at our institution from 2011 to 2016; with the aim to investigate the epidemiology, microbiologic spectrum, and outcomes in patients with post-HT MDRO infections, classified as multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) using standardized definitions. RESULTS: Of the 149 HT recipients, 82 episodes of bacterial infection were seen in 46 patients (31%) in the year following HT. Thirty (37%) were due to MDR pathogens and 13 (16%) were XDR. The most common gram-negative MDR pathogens were extended-spectrum beta-lactamase (ESBL) Escherichia coli and Klebsiella pneumoniae; while XDR pathogens were most commonly Pseudomonas aeruginosa followed by carbapenem-resistant Klebsiella pneumoniae. Majority of infection episodes were bloodstream (54, 66%) followed by pulmonary infection (20, 24%). Within a year after transplant, HT recipients with any bacterial infection had significantly higher mortality versus those without infection; and XDR infections were associated with a 26-fold greater hazard of death on average compared to those without infection (adjusted HR, 26.1; 95% CI, 6.4-107.0; P < .001). There were no PDR infections. CONCLUSION: Bacterial infections were a significant predictor of 1-year post-HT mortality, which was highest among those with XDR infections. This study highlights the burden of MDRO infections in HT recipients and identifies an area of future research.

Sanitary alert: acute gastroenteritis associated with house-fly infestation after heavy rainfall in Karachi, Pakistan.

Not available.

Isolation of antibiotic-resistant gram-negative organisms from donor respiratory culture does not impact non-lung solid organ recipient management.

BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) gram-negative bacteria may be transmitted from organ donors to solid organ transplant recipients and are associated with poor outcomes post-transplant. METHODS: We reported the prevalence of MDR/XDR gram-negative respiratory colonization among 702 deceased organ donors in the New York City area from 2011 to 2014 and performed chart reviews for a subset of recipients to determine whether donor respiratory culture results were predictive of subsequent recipient infection or used to guide post-transplant antimicrobial therapy. RESULTS: Fifty donors (7% of the cohort) had MDR or XDR gram-negative bacteria isolated from endotracheal aspirate or bronchoalveolar lavage culture. Organs from these 50 donors were transplanted into 120 recipients; chart review was performed for 89 of these recipients (38 kidney, 32 liver, 11 heart, 6 kidney/pancreas, 1 liver/kidney, 1 lung). None of the 89 recipients of organs from donors with MDR/XDR gram-negative respiratory colonization were reported to have a donor-derived infection post-transplant, and chart review for the 88 non-lung recipients indicated that peri-transplant antibiotics were not adjusted specifically for donor respiratory culture results. CONCLUSION: These results suggest that donor respiratory culture results are not predictive of post-transplant infection in non-lung recipients and are unlikely to impact post-transplant management.

Hemophagocytic Lymphohistiocytosis Due to Primary HHV-8 Infection in a Liver Transplant Recipient.

Human herpesvirus-8 (HHV-8) remains best known as an oncogenic virus, but nonneoplastic disease manifestations, such as bone marrow failure or hemophagocytic lymphohistiocytosis (HLH) have gained greater recognition in recent years. In organ transplantation, HHV-8 infection commonly occurs with reactivation of latent virus among recipients from endemic regions of the world or due to transmission from the organ donor. We describe a case of HHV-8-associated HLH in a liver transplant recipient at increased risk for primary infection. Our case highlights the risk of non-donor-derived, posttransplant primary HHV-8 infection, and demonstrates that HLH can be a life-threatening complication of this infection.