Citations

AbstractBackgroundToll‐like receptor 3 (TLR3) is implicated in the pathogenesis of viral diseases owing to its ability to recognize viral double‐stranded RNA. We hypothesized that single nucleotide polymorphism (SNP) in TLR3 gene that impairs the function of the protein‐receptor influences the outcome of hepatitis C virus (HCV) infection after liver transplantation.MethodsThe clinical characteristics of 611 liver recipients (HCV‐infected: n = 153, non‐HCV‐infected: n = 458) were assessed to investigate the impact of TLR3 L412F SNP on transplant outcomes.ResultsTLR3 L412F is common, and it was significantly more prevalent among the HCV‐infected cohort (57.5% vs. 45.2%, P = 0.008). In a multivariate analysis, TLR3 L412F was significantly associated with chronic hepatitis C (odds ratio: 1.73, 95% confidence interval [CI]: 1.13–2.65, P = 0.01). In an analysis that compared HCV‐infected patients with wild‐type versus TLR3 L412F, a marginally higher rate of allograft failure and mortality was observed in the TLR3 L412F group (44.3% vs. 30.8%, P = 0.09). However, in a multivariate analysis, only donor age was significantly associated with allograft failure and mortality (relative risk: 1.04, 95% CI: 1.007–1.06, P = 0.02).ConclusionTLR3 L412F is significantly common in HCV‐infected liver recipients, and may be associated with worse outcomes. However, larger studies are needed to determine its significant association with allograft failure and mortality after liver transplantation for chronic hepatitis C.

Abstract Transmission of pathogens from donor to recipient is a potential complication of organ transplantation. Herein, we describe the clinical course and outcomes of 4 transplant recipients who received tissues from a donor with multi‐organ infection with Klebsiella pneumoniae carbapenemase ( KPC )‐producing K. pneumoniae . Recipient 1 underwent simultaneous liver and kidney transplantation for alpha‐1 antitrypsin deficiency and alcohol‐related cirrhosis, and acute tubular necrosis, respectively. Soon after transplantation, he developed an infected hematoma and peritonitis due to KPC ‐producing K. pneumoniae despite receiving tigecycline prophylaxis. He was treated with a prolonged course of tigecycline, amikacin, and meropenem, in conjunction with surgical evacuation and percutaneous drainage of the infected fluid collections. Recipient 2 underwent living‐donor liver transplantation for cholangiocarcinoma and primary sclerosing cholangitis using vein graft from the donor infected with KPC ‐producing K. pneumoniae . Culture of the preservation fluid containing the vein graft was positive for KPC ‐producing K. pneumoniae . The patient received preemptive amikacin and tigecycline, and he did not develop any infection (as evidenced by negative surveillance blood cultures). The isolates from the donor and Recipients 1 and 2 were indistinguishable by pulsed‐field gel electrophoresis. Recipients 3 and 4 underwent kidney and heart transplantation, respectively; both patients received perioperative tigecycline prophylaxis and did not develop infections due to KPC ‐producing K. pneumoniae . All transplant recipients had good short‐term outcomes. These cases highlight the importance of inter‐institutional communication and collaboration to ensure the successful management of recipients of organs from donors infected with multidrug‐resistant organisms.

AbstractHuman herpesvirus‐6 (HHV‐6) is unique among human herpesviruses because of its ability to integrate into chromosomes. This entity, termed chromosomally integrated HHV‐6 (CIHHV‐6), is often mistaken for active infection and treated unnecessarily. The clinical significance of CIHHV‐6 in transplant recipients is not defined. Herein, the clinical characteristics of 7 liver transplant patients with CIHHV‐6 from our recent study, together with 14 other published cases of CIHHV‐6 were reviewed. Of the 21 cases, CIHHV‐6B was reported most commonly among solid organ transplant recipients, while CIHHV‐6A was mostly seen in allogeneic hematopoietic stem cell recipients. None of the 21 patients developed clinical symptoms related to HHV‐6 after transplantation. However, antiviral therapy was administered to 5 asymptomatic patients mistaken to have HHV‐6 infection because of their very high HHV‐6 DNA levels, 3 who developed symptomatic cytomegalovirus disease, and 1 with graft‐versus‐host disease that was mistaken for HHV‐6 infection. In patients who received antiviral therapy, there was no apparent decline in HHV‐6 DNA load, although change in viral kinetics is difficult to discern in the setting of high baseline HHV‐6 DNA load. Clinicians should be aware of this entity of CIHHV‐6 so that antiviral therapy can be considered in the proper clinical context.

Abstract:BackgroundThe clinical features and outcome of prosthetic joint infection (PJI) among solid organ transplant (SOT) recipients have not been characterized. We performed a retrospective, matched case‐control study to examine potential risk factors.MethodsWe reviewed cases ofPJIamong transplant recipients who were evaluated at the Mayo Clinic between 1989 and 2009. Cases were matched to non‐infected controls based on transplant type, prosthetic joint type, and order of organ transplantation/joint implantation.ResultsAmong 367 patients with both a joint prosthesis and anSOT, there were 12 cases of infection in those receiving immunosuppression. These occurred in 8 renal recipients, 3 liver recipients, and 1 heart transplant recipient. Six subjects had hip and 6 had knee arthroplasty infections. The observed time to prosthesis failure ranged from 0.5 to 148 months after implantation. Gram‐positive bacteria (staphylococci and streptococci) caused the infection in 8 subjects. Two cases were caused by nontuberculous mycobacteria, whereas the remaining 2 cases were culture‐negative in the setting of antimicrobial use. We did not find a statistically significant association between obesity, diabetes mellitus, or antimicrobial prophylaxis (given in the setting of immunosuppression) and development ofPJI. A marginal association was seen betweensurgical site infectionand the risk ofPJI; however, this did not reach statistical significance.ConclusionIn our series, infection was mainly caused by gram‐positive bacterial pathogens, similar to the commonly encountered organisms in the immunocompetent host, although opportunistic pathogens were also isolated.

SUMMARY Chromosomally integrated human herpesvirus 6 (ciHHV‐6) is a condition in which the complete HHV‐6 genome is integrated into the host germ line genome and is vertically transmitted in a Mendelian manner. The condition is found in less than 1% of controls in the USA and UK, but has been found at a somewhat higher prevalence in transplant recipients and other patient populations in several small studies. HHV‐6 levels in whole blood that exceed 5.5 log10 copies/ml are strongly suggestive of ciHHV‐6. Monitoring DNA load in plasma and serum is unreliable, both for identifying and for monitoring subjects with ciHHV‐6 due to cell lysis and release of cellular DNA. High HHV‐6 DNA loads associated with ciHHV‐6 can lead to erroneous diagnosis of active infection. Transplant recipients with ciHHV‐6 may be at increased risk for bacterial infection and graft rejection. ciHHV‐6 can be induced to a state of active viral replication in vitro . It is not known whether ciHHV‐6 individuals are put at clinical risk by the use of drugs that have been associated with HHV‐6 reactivation in vivo or in vitro . Nonetheless, we urge careful observation when use of such drugs is indicated in individuals known to have ciHHV‐6. Little is known about whether individuals with ciHHV‐6 develop immune tolerance for viral proteins. Further research is needed to determine the role of ciHHV‐6 in disease. Copyright © 2011 John Wiley & Sons, Ltd.

Abstract:BackgroundRespiratory syncytial virus (RSV) infections range from upper respiratory illness to severe lower respiratory disease. There is no universally accepted treatment for RSV in solid organ transplant (SOT) recipients.MethodsRetrospective review of adult SOT patients with RSV infections, between January 2007 and December 2009, in a single transplant center was performed.ResultsDuring the 3‐year period, a total of 24 adults developed RSV infection, including 12 (50%) SOT recipients (5 kidneys, 4 livers, and 3 lungs). Most cases were seen in 2009 during the influenza H1N1 pandemic, likely as a result of increased testing. In 83% of the cases, the diagnosis was based on RSV antigen detection, which was also used to follow subsequent shedding (mean duration: 20.6 days). Most of the cases presented with lower respiratory disease and required hospitalization. All the patients were on at least two classes of immunosuppressive drugs. We observed a lower lymphocyte count in patients with lower respiratory tract infection. Computed tomography was superior to chest x‐ray in demonstrating pulmonary disease, with the most common findings being pulmonary nodules and ground‐glass opacities. Novel radiographic findings were small cavities and pleural effusions. No co‐infections were documented, and no mortality could be attributed to RSV. Inhaled or oral ribavirin was administered in 67% of the cases, with variations in the treatment regimens.ConclusionSOT recipients accounted for half of all adult cases of RSV at our institution. Type and length of treatment varied widely, and we cannot conclude that outcomes differed between treatments with oral or inhaled ribavirin. Current therapeutic management of RSV in SOT is empiric, and can be rather expensive and difficult, without clear evidence of effectiveness.

ABSTRACT Nystatin is an antifungal compound with potent proinflammatory properties. Herein, we demonstrate that nystatin induces interleukin (IL)-1β, IL-8, and tumor necrosis factor alpha secretion through its activation of toll-like receptor 1 (TLR1) and TLR2. Hence, a TLR-dependent mechanism could serve as the molecular basis for the proinflammatory properties of nystatin.

ABSTRACT Amphotericin B (AmB) is a ligand of toll-like receptor 2 (TLR2). Here, we demonstrate the participation of TLR1 in AmB-induced cell activation that led to the secretion of tumor necrosis factor alpha, interleukin 6 (IL-6), and IL-8. Hence, TLR2-TLR1 coactivation serves as the underlying mechanism for the proinflammatory toxicities associated with AmB.