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Background: Donation after circulatory death (DCD) or hepatitis C virus (HCV+) liver grafts are underused among transplant centers in the United States. The study aimed to evaluate organ utilization and outcomes of liver grafts from DCD donors with HCV infection., Methods: National registry and local center data of all deceased donor liver transplants performed between November 2016 and December 2021 were analyzed. All transplants were divided into 4 groups: HCV- DCD, HCV- donation after brain death [DBD], HCV+ DCD, and HCV+ DBD. The outcome of interest was 1-y graft survival., Results: Out of 146 liver transplant centers in the United States, liver transplants were not performed from DCD donors, HCV+ donors, and a combination of DCD and HCV+ donors by 28.7%, 27%, and 70%-72% of centers, respectively. In multivariate analysis, increasing center acceptance ratio was associated with increased utilization of liver grafts from DCD HCV- and DCD HCV antibody-positive nucleic acid test negative donors. Nationally, 1-y graft survival of HCV- DCD liver grafts was lower compared with other groups (89% versus 92% HCV+ DCD versus 93% HCV+ DBD versus 92% HCV- DBD, log rank P < 0.0001). There was no difference in 1-y graft survival among groups locally., Conclusions: Liver grafts from HCV+ DCD donors have 1-y patient and graft survival comparable with DBD liver grafts from donors with or without HCV infection. These results encourage the widespread use of liver grafts from DCD and HCV+ donors and standardization of practice in DCD donation to expand the donor pool without compromising short-term outcomes., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Pancreas transplant biopsy practices for the diagnosis of rejection or other pathologies are not well described., Methods: We conducted a survey of staff at US pancreas transplant programs (March 22, 2022, to August 22, 2022) to assess current program practices and perceptions about the utility and challenges in the performance and interpretation of pancreas allograft biopsies., Results: Respondents represented 65% (76/117) of active adult pancreas transplant programs, capturing 66% of recent pancreas transplant volume in the United States. Participants were most often nephrologists (52%), followed by surgeons (46%), and other staff (4%). Pancreas allograft biopsies were performed mostly by interventional radiologists (74%), followed by surgeons (11%), nephrologists (8%), and gastroenterologists (1%). Limitations in the radiologist's or biopsy performer's comfort level or expertise to safely perform a biopsy, or to obtain sufficient/adequate samples were the two most common challenges with pancreas transplant biopsies. Pancreas transplant biopsies were read by local pathologists at a majority (86%) of centers. Challenges reported with pancreas biopsy interpretation included poor reliability, lack of reporting of C4d staining, lack of reporting of rejection grading, and inconclusive interpretation of the biopsy. Staff at a third of responding programs (34%) stated that they rarely or never perform pancreas allograft biopsies and treat presumed rejection empirically., Conclusions: This national survey identified significant variation in clinical practices related to pancreas allograft biopsies and potential barriers to pancreas transplant utilization across the United States. Consideration of strategies to improve program experience with percutaneous pancreas biopsy and to support optimal management of pancreas allograft rejection informed by histology is warranted., Competing Interests: K.L.L. is supported by the Mid-America Transplant/Jane A. Beckman Endowed Chair in Transplantation and the National Institute of Diabetes and Digestive and Kidney Diseases grant R01DK120551. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors declare no funding or conflicts of interest.

Background: Cytomegalovirus (CMV) donor-positive/recipient-negative (D+R-) serostatus is independently associated with worse allograft and patient survival across solid organ transplant (SOT) types. We characterized trends in CMV D+R- serostatus among adult SOT recipients performed in the United States., Methods: Donor (D) and recipient (R) CMV serostatus and demographic factors were obtained from the Scientific Registry of Transplant Recipients for persons ≥18 y undergoing a first SOT between January 1, 2000, and December 31, 2020. The proportions of D+R- SOTs over time were assessed using Chi square for trend and modeled through 2040. Factors associated with D/R seropositivity were assessed using logistic models., Results: Among 472 549 SOTs, the average proportion of D+R- SOTs increased significantly among kidney, liver, heart, and lung between 2000 to 2009 and 2010 to 2020: 18.0% to 18.3% ( P  = 0.034), 19.4% to 21.8% ( P  < 0.001), 22.2% to 25.5% ( P  < 0.001), and 23.6% to 27.0% ( P  < 0.001), respectively. The increased proportion over time resulted from a disproportionate increase in R- (34.9% to 37.0% for all organ types, P  < 0.001) and a smaller corresponding change in D+ (60.8% to 60.3%, P  < 0.001)., Conclusions: The proportion of high-risk CMV D+R- SOTs increased significantly across all organs and is projected to continue to increase. These findings inform population-level strategies to mitigate the negative impact of CMV D+R- in SOT., Competing Interests: A.P.L. has received consulting fees, research support, contracted research, or consulting fees from: Amplyx Pharmaceuticals, Novartis, Merck, J&J, NovoNordisc, GSK, NobelPharma, Hologic, and Allovir. The other authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Risk factors, virological parameters, and outcomes associated with HHV-6 viremia in high-risk donor CMV-seropositive and recipient CMV-seronegative (D+R-) liver transplant recipients in the current era are incompletely defined., Methods: The study population consisted of patients in the preemptive therapy (PET) arm of a randomized, controlled trial of PET versus valganciclovir prophylaxis for CMV prevention in D+R- liver transplant recipients. Weekly blood samples through 100 d in the PET group were tested for HHV-6 viremia using a real-time quantitative polymerase chain reaction. Assessments included virological characteristics and relationship with CMV, risk factors, and impact of HHV-6 viremia with outcomes through 12 mo posttransplant., Results: HHV-6 viremia at any level developed in 42% (40 of 96). Older patient age (P = 0.03), longer hospitalization (P = 0.015), and ICU stay at transplantation (P = 0.029) were significantly associated with high-grade viremia. Concurrent HHV-6 and CMV viremia was associated with earlier onset of HHV-6 viremia (P = 0.004), higher HHV-6 area under the curve (P = 0.043), and higher peak HHV-6 viral load (P = 0.006) versus HHV-6 viremia alone. High-grade viremia was independently associated with biopsy-proven rejection within 12 mo (P = 0.045) posttransplant., Conclusions: Among D+R- liver transplant recipients receiving valganciclovir as PET, high-grade HHV-6 viremia was associated with increased age and critical illness in ICU at time of transplant and was independently associated with allograft rejection., Competing Interests: D.J.W. has received research support form Merck, Chimerix, Shire, Gilead, and Oxford Immnotech. G.M.L. has received research support from Takeda pharmaceutical company. F.P.S. has received research support from Shire, Ansun, and Novartis. A.P.L. has received research support from Merck and Astellas, and consulting support from Helocyte, Inc, Amplyx, Novartis, and AlloVir. The other authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors declare no funding or conflicts of interest.

Invasive aspergillosis and mucormycosis are life-threatening infections in solid organ and hematopoietic cell transplant recipients. Despite medical advancements in the care of these patients and the availability of new mold-active drugs, the outcomes remain suboptimal. Therefore, there has been increased interest in the use of combination antifungal therapy, in hopes that leveraging the possible in vitro synergy of these agents will improve the prognosis of invasive mold disease. However, there has been a large disconnect between the results of experimental and clinical investigations, as clinical studies have not unequivocally demonstrated the superiority of combination therapy over monotherapy. This is particularly true for mucormycosis, where the rarity of the condition has made it nearly impossible to prospectively study novel therapeutic strategies. We review the current standard of antifungal therapy and the preclinical and clinical data addressing the merit of combination therapy, and we provide guidance to optimize the management of these mycoses.

HIV-infected persons who achieve undetectable viral loads on antiretroviral therapy currently have near-normal lifespans. Liver disease is a major cause of non-AIDS-related deaths, and as a result of longer survival, the prevalence of end-stage renal disease in HIV is increasing. HIV-infected persons undergoing organ transplantation generally achieve comparable patient and graft survival rates compared to their HIV-uninfected counterparts, despite a nearly threefold increased risk of acute rejection. However, the ongoing shortage of suitable organs can limit transplantation as an option, and patients with HIV have higher waitlist mortality than others. One way to solve this problem would be to expand the donor pool to include HIV-infected individuals. The results of a South Africa study involving 27 HIV-to-HIV kidney transplants showed promise, with 3- and 5-year patient and graft survival rates similar to those of their HIV-uninfected counterparts. Similarly, individual cases of HIV-to-HIV liver transplantation from the United Kingdom and Switzerland have also shown good results. In the United States, HIV-to-HIV kidney and liver transplants are currently permitted only under a research protocol. Nevertheless, areas of ambiguity exist, including streamlining organ allocation practices, optimizing HIV-infected donor and recipient selection, managing donor-derived transmission of a resistant HIV strain, determining optimal immunosuppressive and antiretroviral regimens, and elucidating the incidence of rejection in HIV-to-HIV solid organ transplant recipients.

Background: The utility of Aspergillus galactomannan (GM) and β-D-glucan (BG) in liver transplant recipients remains uncertain., Methods: As part of a randomized, double-blind trial of antifungal prophylaxis in liver transplant recipients at risk for invasive fungal infections (IFIs), GM and BG were assessed in 199 patients at baseline (enrollment) and weekly thereafter for the duration of study drug. Receiver operating characteristic (ROC) analysis was used to evaluate the accuracy of these for the diagnosis of IFIs., Results: Overall, 46.4% of the patients at baseline had positive GM (index ≥ 0.5) and 89.6% had BG of 80 pg/mL or greater with BG level of 500 pg/mL or greater in 31.8%. Patients with invasive aspergillosis (IA) (3/3) had positive GM at baseline as did 45.5% of those without IA (P = 0.098); the area under the ROC curve for the diagnosis of IA was 0.77 (fair test, ie, good sensitivity but poor specificity). Using BG cutoff of 80 pg/mL or higher, 100% (12/12) of the patients with IFI had positive baseline BG and as did 88.9% (160/180) of those without IFI (P = 0.618); the area under the ROC curve for predicting IFIs was 0.56 (poor test). In multivariate analyses, GM positivity was associated with study site (P = 0.041), and BG positivity with renal replacement therapy (P = 0.05) and study site (P = 0.01). The GM and BG levels declined over time; positivity at subsequent time points was lower in comparison with baseline (P < 0.001)., Conclusions: The GM and BG tests had significant center variability and limited accuracy for the diagnosis of IFIs in high-risk liver transplant recipients.

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.

Background: Limited data exist regarding echinocandins as antifungal prophylaxis in liver transplant recipients., Methods: The efficacy and safety of targeted prophylaxis with micafungin or amphotericin B lipid complex (ABLC) was assessed in a sequential cohort of high-risk patients (posttransplantation dialysis, retransplantation, or reoperation) and compared with those without high risk who did not receive prophylaxis. Outcomes were assessed at 90 days., Results: Micafungin versus ABLC recipients were older (P=0.0065) and more likely to have hepatocellular carcinoma (P=0.025). High-risks, that is, dialysis (55.6% vs. 79.2%), retransplantation (5.6% vs. 12.5%), and reoperation (38.9% vs. 20.8%) did not differ between the two groups. Invasive fungal infections developed in 11.1% (2 of 18) of micafungin recipients, 8.3% (2 of 24) of ABLC recipients, and 3% (7 of 234) of patients without high risks (P=0.12). In nondialyzed patients, ABLC versus micafungin recipients had significantly higher serum creatinine on day 14 (P=0.04). However, renal and hepatic function, rejection, graft loss, and mortality did not differ for the two groups on day 90., Conclusions: Targeted prophylaxis with micafungin or ABLC decreased the risk of mycoses in high-risk recipients compared with that in low-risk recipients. Compared with ABLC, however, micafungin appeared to be associated with lower early-renal dysfunction and no additional risk of hepatic dysfunction.

Background: Incidence, characteristics, and risk factors for tuberculosis (TB)-associated immune reconstitution inflammatory syndrome (IRS) in solid-organ transplant (SOT) recipients are not known., Methods: Patients are composed of 64 consecutive SOT recipients with TB followed for 12 months. IRS was defined based on previously proposed criteria., Results: IRS developed in 14% (9/64) of the patients, a median of 47 days after the use of anti-TB therapy. Liver versus other types of organ transplant recipients (adjusted odds ratio [OR], 6.11; 95% confidence interval [CI], 1.08-34.86), prior cytomegalovirus infection (adjusted OR, 5.65; 95% CI, 0.93-34.47), and rifampin use (adjusted OR, 4.56; 95% CI, 0.74-27) were associated with a higher risk of IRS. The presence of more than one factor (liver transplantation, cytomegalovirus infection, and rifampin use) when compared with none of these factors conferred a 19-fold increase in the risk of IRS (P=0.01). Mortality at 1 year after diagnosis was 33.3% in patients with IRS and 17.2% in those without IRS (P=0.31)., Conclusions: IRS was documented in 14% of the SOT recipients with TB. We determined clinically identifiable factors that may be useful in assessing the risk of tuberculosis-associated posttransplantation IRS.

Background: The utility of cardiac stress testing as a risk-stratification tool before kidney transplantation remains debatable owing to discordance with coronary angiography and outcome yields at different centers., Methods: We conducted a retrospective study of 273 diabetic kidney transplant recipients from 2006 to 2010. By protocol, all diabetic patients underwent pharmacological radionucleotide stress test or dobutamine stress echocardiography before transplant. We compared the 1-year cardiac outcomes between those with negative stress test results and those with positive stress test results., Results: Patients with a positive stress test result (n=67) underwent coronary angiogram, and significant coronary artery disease (≥70% coronary stenosis) was found in 35 (52.2%) patients. Of the latter, 32 (91.4%) underwent cardiac revascularization (24 underwent cardiac stenting and 8 underwent coronary artery bypass grafting). The rest (n=35) were treated medically. Within 1 year after transplant, the group with positive stress test results experienced more cardiac events (34.3% vs. 3.9%, P<0.001) including acute myocardial infarction (22.4% vs. 3.4%, P<0.001) and ventricular arrhythmias (8.9% vs. 0.05%, P=0.001), higher all-cause mortality (19.4% vs. 4.8%, P<0.001), and cardiac mortality (17.9% vs. 0.9%, P<0.001) compared with the group with negative stress test results., Conclusions: In this diabetic population, stress testing showed positive and negative predictive values of 34.3% and 96.1%, respectively. Pharmacological cardiac stress testing provided excellent risk stratification in diabetic kidney transplant recipients.

Background: The clinical significance of pretransplant donor-specific antibodies (pre-Tx DSAs) detected by single-antigen bead flow cytometry (SAB-FC) remains unclear., Methods: To investigate the impact that pre-Tx DSAs detected by SAB-FC have on early clinical outcomes, we tested pre-Tx sera from all consecutive deceased-donor kidney transplants performed between January 2005 and July 2006 (n=237)., Results: In the study population of which 66% had a high-immunologic risk, mean fluorescence intensity (MFI) more than or equal to 100 for class I and more than or equal to 200 for class II were the lowest DSA thresholds associated with inferior antibody-mediated rejection-free graft survival (75% vs. 90%, P=0.004 and 76% vs. 87%, P=0.017, respectively). The hazard ratio for antibody-mediated rejection increased linearly with higher class II DSA from MFI 100 to 800 (1.7[0.8-3.2], P=0.1 for MFI ≥100 vs. 4.7[2.4-8.8], P<0.001 for MFI ≥ 800). Differences in graft function were only evident in patients with class II MFI more than or equal to 500 (estimated glomerular filtration rate: 47.6 vs. 54.3, P=0.02 and proteinuria: 0.6 ± 0.6 vs. 0.4 ± 0.3, P=0.03). A difference in death-censored graft survival was detected in patients with class II MFI more than or equal to 1000 (75% vs. 91.9%, P=0.055)., Conclusion: High-pre-Tx DSAs detected by SAB-FC are associated with incrementally poor graft outcomes in deceased-donor kidney transplant with high-immunologic risk.

Background: Rhino-orbital-cerebral disease is a significant manifestation of zygomycosis in solid organ transplant (SOT) recipients. However, its characteristics and outcome are not well addressed., Methods: SOT recipients with zygomycosis as per the European Organization for Research and Treatment in Cancer and the Mycoses Study Group criteria in a cohort study at our centers published previously and those identified with a PubMed search from the 1950s to November 2009 were studied. Patients with mycosis involving the sinuses, orbits, or central nervous system (CNS) were included., Results: Patients comprised a total of 90 SOT recipients with rhino-orbital-cerebral zygomycosis, including 13 in our cohort and 77 in the literature. CNS disease occurred in 57% (51 of 90). Overall mortality was 52.3% (46 of 88), and the mortality in patients with CNS disease was 73.5% (36 of 49). In logistic regression analysis, older age (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.04-1.21, P=0.002) was associated with a higher mortality rate, whereas lipid formulations of amphotericin B compared with amphotericin B deoxycholate (OR 0.09, 95% CI 0.02-0.50, P=0.006) and surgery (OR 0.12, 95% CI 0.01-0.94, P=0.043) were independently associated with an improved survival even when controlled for CNS involvement and the era of diagnosis of disease., Conclusions: Rhino-orbital-cerebral zygomycosis, particularly CNS disease, is associated with substantial mortality rate in SOT recipients. Older age is a significant risk factor for mortality, whereas lipid formulations of amphotericin B and surgery improved outcomes.

Background: Cerebrospinal fluid (CSF) analysis is often deferred in patients with cryptococcal disease, particularly in the absence of neurologic manifestations. We sought to determine whether a subset of solid organ transplant (SOT) recipients with high likelihood of central nervous system (CNS) disease could be identified in whom CSF analysis must be performed., Methods: Patients comprised a multicenter cohort of SOT recipients with cryptococcosis., Results: Of 129 (88%) of 146 SOT recipients with cryptococcosis who underwent CSF analysis, 80 (62%) had CNS disease. In the overall study population, abnormal mental status, time to onset of cryptococcosis more than 24 months posttransplantation (late-onset disease), serum cryptococcal antigen titer more than 1:64, and fungemia were independently associated with an increased risk of CNS disease. Of patients with abnormal mental status, 95% had CNS cryptococcosis. When only patients with normal mental status were considered, three predictors (serum antigen titer >1:64, fungemia, and late-onset disease) independently identified patients with CNS cryptococcosis; the risk of CNS disease was 14% if none, 39% if one, and 94% if two of the aforementioned predictors existed (chi for trend P<0.001)., Conclusions: CSF analysis should be strongly considered in SOT recipients with cryptococcosis who have late-onset disease, fungemia, or serum cryptococcal antigen titer more than 1:64 even in the presence of normal mental status.

Background: Prognostic implications of cryptococcal antigen and outcomes associated with central nervous system (CNS) cryptococcal lesions in solid organ transplant recipients have not been fully defined., Methods: Patients were derived form a cohort of 122 solid organ transplant recipients with cryptococcosis in a multicenter study from 1999 to 2006., Results: Central nervous system cryptococcosis was documented in 61 patients. Serum or cerebral spinal fluid antigen titers did not correlate with mortality at 90 days or cerebral spinal fluid sterilization at 2 weeks. Central nervous system lesions were identified in 16 patients and included leptomeningeal lesions in eight, parenchymal lesions in six, and hydrocephalus in two. Overall, 13/16 CNS lesions were present at the time of diagnosis. One parenchymal and two hydrocephalus lesions, however, developed after diagnosis and fulfilled the criteria for immune reconstitution syndrome. Cerebral spinal fluid antigen titers were higher with meningeal versus parenchymal lesions, and hydrocephalus (P=0.015). Mortality was 50% (3/6) for patients with parenchymal, 12.5% (1/8) for those with leptomeningeal, and 0/3 for patients with hydrocephalus. Mortality was 31% (4/13) for patients with CNS lesions at baseline and 0/3 in those with new onset lesions., Conclusions: Despite a higher antigen titer with meningeal lesions, outcomes tended to be worse with parenchymal compared with meningeal lesions or hydrocephalus. New onset CNS lesions may represent immune reconstitution syndrome and seemed to be associated with better outcome.

Background: The clinical utility of Platelia Aspergillus enzyme immunoassay (EIA) for galactomannan (GM) antigen detection in bronchoalveolar lavage (BAL) for the diagnosis of invasive aspergillosis (IA) in lung transplant recipients is not known., Methods: BAL fluid samples from consecutive lung transplant recipients who underwent bronchoscopy were prospectively analyzed for GM., Results: A total of 333 BAL samples from 116 patients were tested. Invasive aspergillosis was documented in 5.2% (6/116) of the patients. Samples analyzed included 9 BALs from two patients with proven IA, 19 BALs from four patients with probable IA, and 305 BALs from 110 patients without IA. At the index cutoff value of > or =0.5, the sensitivity was 60%; specificity was 95%, with positive and negative likelihood ratios of 14 and 0.41, respectively. Increasing the index cutoff value to > or =1.0 yielded a sensitivity of 60%, a specificity of 98%, and the positive and negative likelihood ratios of 28 and 0.40, respectively. Two of six patients with IA receiving antifungal prophylaxis had false-negative results., Conclusions: A Platelia EIA index cut-off > or =1.0 in the BAL fluid in a lung transplant recipient with a compatible clinical illness may be considered as suggestive of IA.

Background: : The efficacy of the combination of voriconazole and caspofungin when used as primary therapy for invasive aspergillosis in organ transplant recipients has not been defined., Methods: : Transplant recipients who received voriconazole and caspofungin (n=40) as primary therapy for invasive aspergillosis (proven or probable) in a prospective multicenter study between 2003 and 2005 were compared to a control group comprising a cohort of consecutive transplant recipients between 1999 and 2002 who had received a lipid formulation of AmB as primary therapy (n=47). In vitro antifungal testing of Aspergillus isolates to combination therapy was correlated with clinical outcome., Results: : Survival at 90 days was 67.5% (27/40) in the cases, and 51% (24/47) in the control group (HR 0.58, 95% CI, 0.30-1.14, P=0.117). However, in transplant recipients with renal failure (adjusted HR 0.32, 95% CI: 0.12-0.85, P=0.022), and in those with A. fumigatus infection (adjusted HR 0.37, 95% CI: 0.16-0.84, P=0.019), combination therapy was independently associated with an improved 90-day survival in multivariate analysis. No correlation was found between in vitro antifungal interactions of the Aspergillus isolates to the combination of voriconazole and caspofungin and clinical outcome., Conclusions: : Combination of voriconazole and caspofungin might be considered preferable therapy for subsets of organ transplant recipients with invasive aspergillosis, such as those with renal failure or A. fumigatus infection.

Background: Therapeutic practices for Cryptococcus neoformans infection in transplant recipients vary, particularly with regards to antifungal agent employed, and duration of therapy. The risk of relapse and time to recurrence is not known. We assessed antifungal treatment practices for cryptococcosis in a cohort of prospectively followed organ transplant recipients., Methods: The patients comprised 83 transplant recipients with cryptococcosis followed for a median of 2.1 and up to 5.2 years., Results: Patients with central nervous system infection (69% vs. 16%, P = 0.00001), disseminated infection (82.7% vs. 20%, P = 0.00001), and fungemia (29% vs. 8%, P = 0.046) were more likely to receive regimens containing amphotericin B than fluconazole as primary therapy. The use of fluconazole, on the other hand, was more likely for infection limited to the lungs (64% vs. 14%, P = 0.00002). Survival at 6 months tended to be lower in patients whose CSF cultures at 2 weeks were positive compared to those whose CSF cultures were negative (50% vs. 91%, P = 0.06). Maintenance therapy was employed in 68% (54/79) of the patients who survived >3 weeks. The median duration of maintenance therapy was 183 days; 55% received maintenance for > or = 6 months and 25% for >1 year. Relapse was documented in 1.3% (1/79) of the patients., Conclusions: A majority of the organ transplant recipients with cryptococcosis receive maintenance antifungal therapy for 6 months with low risk of relapse. These data can assist in trials to assess the optimal therapeutic approach and duration of therapy for cryptococcosis in transplant recipients.

This study describes the association of allograft loss and immune reconstitution syndrome (IRS) in the course of Cryptococcosis neoformans infection in renal transplant recipients. Patients comprised 54 renal allograft recipients with cryptococcosis in a prospective, multicenter study. IRS developed in 5.5% (3/54) of the renal transplant recipient with C. neoformans infection. The renal allograft was lost to chronic rejection in 66% (2/3) of the patients with cryptococcosis who developed IRS compared to 5.9% (3/51) of those who did not (P=0.012). Kaplan-Meier survival analysis showed that subsequent to cryptococcal infection the probability of allograft survival was significantly lower in patients who developed IRS compared to those who did not develop IRS (P=0.0004). Temporal association of graft loss with IRS suggests a common pathophysiologic basis for these entities with implications relevant for the optimal management of renal transplant recipients with cryptococcosis.

Background: The effect of preemptive therapy on indirect sequelae associated with cytomegalovirus (CMV) in liver-transplant recipients has not been clearly delineated., Methods: Thirteen years of outcome with the use of preemptive therapy were assessed in a cohort of 216 consecutive liver-transplant recipients., Results: The incidence of major infections (31% vs. 44.3%), bacterial infections (31% vs. 39.2%), bacteremia (19% vs. 29.1%), or fungal infections (3.4% vs. 7.6%) did not differ significantly for patients with CMV infection who received preemptive therapy compared with those who never developed CMV infection and did not receive antiviral prophylaxis for CMV (P>0.20 for all variables). The rate of opportunistic infections also did not differ when patients were stratified by primary CMV infection, reactivation infection, or no CMV infection. Recurrent hepatitis C virus (HCV) hepatitis occurred in 55.6% of the patients with CMV treated with preemptive therapy and 49.8% of those without CMV infection (P>0.20). The probability of survival at 6 months, 12 months, 2 years, and 3 years was also comparable for the two groups., Conclusions: Liver-transplant recipients with CMV infection, including high-risk R-/D+ patients, when followed using the preemptive therapy approach had no significant difference in meaningful outcomes such as opportunistic superinfections, HCV recurrence rates, rejection, and survival when compared with the patients in whom CMV infection never developed and who did not receive antiviral prophylaxis for CMV.

Background: The efficacy of valganciclovir used as preemptive therapy for cytomegalovirus (CMV) disease in liver transplant recipients is not known., Methods: Between 1996 and 2004, surveillance testing using CMV antigenemia was performed at weeks 2, 4, 6, 8, 10, 12, and 16 posttransplant. A total of 28.8% (17/59) of the patients from 2001 to 2004 with antigenemia who received valganciclovir as preemptive therapy were compared with 26.2% (21/80) of the patients from 1996 to 2000 who received oral ganciclovir as preemptive therapy., Results: The mean decline in the antigenemia level after initiation of valganciclovir and oral ganciclovir was 80.5% versus 50.7% at 1 week, 99.5% versus 89.4% at 2 weeks, and 100% versus 97.7% at 4 weeks, respectively. A higher proportion of patients who received valganciclovir (64.7%) belonged to the high-risk group (R-/D+) than patients who received oral ganciclovir (33.3%, P=0.10). Recurrent shedding was documented in 47.1% (8/17) of the patients in the valganciclovir group and 28.6% (6/21) of the patients in the oral ganciclovir group (P>0.20). Recurrent shedding correlated significantly with R-/D+ CMV serostatus and baseline CMV antigenemia level, regardless of the study group. No patient in either group developed CMV disease during or after the period of surveillance monitoring. The incidence of opportunistic infections and patient outcome did not differ for the valganciclovir group versus the oral ganciclovir group or patients without CMV infection (P>0.20)., Conclusion: Antigenemia-directed valganciclovir as preemptive therapy seems to be effective for the prevention of CMV disease in liver transplant recipients, including high-risk patients.