C. Koval

Solid Organ Transplantation From Hepatitis B Virus–Positive Donors: Consensus Guidelines for Recipient Management

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non‐liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti‐HBc+) donors. Organs from anti‐HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non‐liver recipients but is not recommended in immune non‐liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost‐effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.

Evolution and impact of drive-line infection in a large cohort of continuous-flow ventricular assist device recipients

BACKGROUND Drive-line infections (DLIs) frequently complicate ventricular assist device (VAD) support. We sought to describe the detailed effects of DLIs over time in patients with continuous-flow VADs, including the onset, risk factors, organisms involved, association with invasive infections, and outcomes. METHODS We reviewed data for patients with HeartMate II VADs (HMII) who were implanted at the Cleveland Clinic from October 2004 to September 2011 and followed through December 2011. DLIs were defined according to published criteria. RESULTS DLIs developed in 45 of 194 HMII VADs over a median period of 232 days (range 22 to 883 days). Hazard for DLI was 2.0%/month, but transiently peaked at 11%/month at 7.5 months after implant. Pseudomonas aeruginosa accounted for 31%, 42% and 55% of initial, final and deep DLIs, respectively. Of the 40 superficial DLIs, 13 (32.5%) became deep. DLI-associated bacteremia and hospitalization occurred in 14 of 45 (31%) and 30 of 45 (67%), respectively. All patients received antibiotics (median 171 days), but only 3 of 44 (6.8%) developed an antibiotic complication. DLIs increased the risk for death while on VAD support (HR 2.20, 95% CI 1.20 to 4.05; p = 0.01). Six and 12 months after DLI, mortality was 9.8% and 31%, but the competing event of transplantation occurred successfully in 20% and 28%, respectively. CONCLUSIONS Most DLIs begin superficially with peak hazard at 7.5 months after implant. Depth of infection and infecting organism may evolve over months on support, with Pseudomonas becoming more prominent. Although effectively managed for prolonged periods, DLIs are associated with reduced survival on VAD support. Earlier transplantation is the most successful approach to treatment.

Invasive fungal infections following liver transplantation: Incidence, risk factors, survival, and impact of fluconazole‐resistant Candida parapsilosis (2003‐2007)

Invasive fungal infections (IFIs) are associated with a high mortality rate for liver transplantation (LT) recipients. To study the incidence of and risk factors for IFIs in LT recipients and the associated mortality rates, we retrospectively reviewed the records of first‐time deceased donor LT recipients (January 2003 to December 2007). The incidence of IFIs was 12%. Non‐albicans Candida species accounted for 55% of IFIs; 50% of these IFIs were Candida parapsilosis. Only 43% of Candida isolates were fluconazole‐susceptible (minimum inhibitory concentration ≤ 8 μ/mL). All C. parapsilosis isolates were fluconazole‐resistant, and this coincided with a surge of these isolates during a peak period of LT. Factors associated with IFIs included a creatinine level > 2 mg/mL [hazard ratio (OR) = 2.4, 95% confidence interval (CI) = 1.2‐5.0, P = 0.01], a Model for End‐Stage Liver Disease score > 25 (OR = 2.4, 95% CI = 1.2‐4.9, P = 0.02), pretransplant fungal colonization (OR = 7.0, 95% CI = 3.2‐15.3, P < 0.001), and a daily prophylactic fluconazole dosage < 200 mg (OR = 2.8, 95% CI = 1.1‐7.4, P = 0.03). According to a multivariate analysis, only pretransplant fungal colonization was associated with IFIs (OR = 7.8, 95% CI = 3.9‐16.2, P < 0.001). The 1‐year patient survival rates with and without IFIs were 41% and 80%, respectively, and the survival rates with C. parapsilosis, other non‐albicans Candida, and Candida albicans IFIs were 28%, 50%, and 75%, respectively. In conclusion, IFIs after LT (especially non‐albicans Candida species and fluconazole‐resistant C. parapsilosis) were associated with reduced survival. The risk factors highlight the importance of pretransplant risk assessments. The identification of pretransplant fungal colonization may allow for risk modifications before or at the time of LT. Additionally, the number of LT procedures and prophylactic strategies may affect institutional outbreaks of resistant Candida strains. Liver Transpl, 2012.

Outcomes associated with surgical management of infections related to the HeartMate II left ventricular assist device: Implications for destination therapy patients.

outcomes among patient groups in which the results are sub-optimal. We believe that immunosuppression protocols, as currently practiced, are sub-optimal for young adults and should be changed. Among young adults, it may be argued that the increased rates of rejection death can be attributed to non-compliance and/or transition from pediatric to adult care. Although there likely exist subgroups within this demographic range that are at higher risk for these reasons, the magnitude of the observed effect is not likely explained solely on the basis of compliance. The outcomes data suggest that studies addressing optimal levels of immunosuppression in this group should be implemented immediately.

Selecting suitable solid organ transplant donors: Reducing the risk of donor-transmitted infections.

Selection of the appropriate donor is essential to a successful allograft recipient outcome for solid organ transplantation. Multiple infectious diseases have been transmitted from the donor to the recipient via transplantation. Donor-transmitted infections cause increased morbidity and mortality to the recipient. In recent years, a series of high-profile transmissions of infections have occurred in organ recipients prompting increased attention on the process of improving the selection of an appropriate donor that balances the shortage of needed allografts with an approach that mitigates the risk of donor-transmitted infection to the recipient. Important advances focused on improving donor screening diagnostics, using previously excluded high-risk donors, and individualizing the selection of allografts to recipients based on their prior infection history are serving to increase the donor pool and improve outcomes after transplant. This article serves to review the relevant literature surrounding this topic and to provide a suggested approach to the selection of an appropriate solid organ transplant donor.

Impact of pretransplant rifaximin therapy on early post–liver transplant infections

Bacterial and fungal infections are major causes of morbidity and mortality after liver transplantation (LT). The role of intestinal decontamination in the prevention of post‐LT infections is controversial. Rifaximin is widely used for the treatment of hepatic encephalopathy. The effect of rifaximin on post‐LT infections is unknown. The aim of our study was to determine the effect of rifaximin therapy in the pretransplant period on early bacterial infections (EBIs) and fungal infections within the first 30 days after LT. All adult patients who underwent LT at our institution (January 2009 to July 2011) were included in this retrospective cohort study. Patients receiving antibiotics other than pretransplant protocol antibiotics were excluded. Patients were stratified into 2 groups based on the presence or absence of rifaximin therapy for at least 2 days before LT. Infections were defined by the isolation of any bacterial or fungal organisms within 30 days of LT. Multivariate regression analysis, Student t tests, and Pearsons chi‐square tests were used to compare the 2 groups. Two hundred sixty‐eight patients were included, and 71 of these patients (26.5%) were on rifaximin at the time of LT. The 2 groups were comparable with respect to age, sex, race, and Model for End‐Stage Liver Disease score. There were no significant differences in the rates of EBIs (30% for the non‐rifaximin group and 25% for the rifaximin group, P = 0.48) or fungal infections between the 2 groups. There was no increase in antimicrobial resistance among the infecting organisms. There was no difference in survival between the rifaximin and non‐rifaximin groups (98% versus 97%, P = 0.36). In conclusion, the use of rifaximin in the pre‐LT period was not associated with an increased risk of bacterial or fungal infections in the early post‐LT period. Liver Transpl 20:544–551, 2014.

Bloodstream Infection Caused by Nontoxigenic Corynebacterium diphtheriae in an Immunocompromised Host in the United States

ABSTRACT Corynebacterium species are well-known causes of catheter-related bloodstream infections. Toxigenic strains of Corynebacterium diphtheriae cause respiratory diphtheria. We report a bloodstream infection caused by a nontoxigenic strain of C. diphtheriae and discuss the epidemiology, possible sources of the infection, and the implications of rapid species identification of corynebacteria.

Cryptococcosis in patients with cirrhosis of the liver and posttransplant outcomes

Background The outcomes and optimal management of cirrhotic patients who develop cryptococcosis before transplantation are not fully known. Methods We conducted a multicenter study involving consecutive patients with cirrhosis and cryptococcosis between January 2000 and March 2014. Data collected were generated as standard of care. Results In all, 112 patients were followed until death or up to 9 years. Disseminated disease and fungemia were present in 76.8% (86/112) and 90-day mortality was 57.1% (64/112). Of the 39 patients listed for transplant, 20.5% (8) underwent liver transplantation, including 2 with active but unrecognized disease before transplantation. Median duration of pretransplant antifungal therapy and posttransplant therapy was 43 days (interquartile range, 8-130 days) and 272 days (interquartile range, 180-630 days), respectively. Transplantation was associated with lower mortality (P = 0.002). None of the transplant recipients developed disease progression during the median follow-up of 3.5 years with a survival rate of 87.5%. Conclusions Cryptococcosis in patients with cirrhosis has grave prognosis. Our findings suggest that transplantation after recent cryptococcal disease may not be a categorical exclusion and may be cautiously undertaken in liver transplant candidates who are otherwise deemed clinically stable.

Donor-derived tuberculosis (TB) infection in lung transplant despite following recommended algorithm.

A 58-year-old man (case–patient) with negative tuberculin skin testing (TST) underwent a double lung transplant in July of 2012 for COPD. The deceased donor was a 42-yearold Vietnamesemanwho emigrated to the United States in 1988 and had died of acute intracranial hemorrhage. The donor did not have any history of TB or positive TST. An ante-mortem CT of the chest showed no infiltrates or granulomas in the lungs. We did not administer TB prophylaxis to the lung transplant recipient based on AST guidelines on diagnosis and management of TB in transplant donors (1). The case–patient developed a cough with a new right pulmonary infiltrate on chest radiograph on posttransplant day 90. He underwent bronchoscopy with BAL which grew pan-susceptible Mycobacterium tuberculosis. All family contacts were well and tested negative for latent TB. The isolate was sent to Ohio Department of Health and to CDC for genotyping.

Progressive Multifocal Leukoencephalopathy in a Heart Transplant Recipient Following Rituximab Therapy for Antibody‐Mediated Rejection

We report the case of a male heart transplant recipient who developed acute antibody‐mediated rejection and was treated with 5 weeks of a rituximab‐containing regimen. Two months later he presented with progressive motor and cognitive impairments and was diagnosed with progressive multifocal leukoencephalopathy (PML). He was treated with reduction of his immunosuppressive medications, mirtazapine, IVIG and plasmapheresis. He died within weeks. We reviewed the current literature on PML and its association with immunosuppression, highlighting its impact in the setting of solid organ transplantation and considering the potential effect of newer biologic drugs on the incidence of this devastating disease in the transplant population.