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Objective: The aim of the study was to determine the clinical characteristics, frequency of opportunistic infections (OI), and the outcomes for liver transplant recipients with severe hepatitis C virus (HCV) recurrence. In addition, the objective was to evaluate HCV recurrence as a risk factor for developing an OI., Methods: We conducted a retrospective observational study recording all liver transplant recipients from July 1, 2003, to December 31, 2012. Patients with liver disease due to HCV were selected. Active surveillance of infections was conducted periodically, and patients were classified according to presence of severe HCV recurrence., Results: Three hundred seventy patients underwent liver transplantation because of chronic HCV. One hundred forty-seven patients presented severe recurrence (SR) (49%) and 50 (17%) of them had post-liver transplant cholestatic hepatitis C. Patients with SR presented OI, especially cytomegalovirus (CMV) infections and invasive fungal infections, more frequently than patients without SR (33% vs 13%; P < .001). From the diagnosis of SR to the presentation of OI, the median number of days was 169 (6-2083). Acute allograft rejection (OR 1.8 95% confidence interval [CI] 1.1-3.3) donor age ≥60 years (OR 2.9 95% CI 1.3-6.8), and SR (OR 2.8, 95% CI 1.6-5.1) were independently associated with the development of OI in liver transplant recipients., Conclusion: A high index of suspicion of opportunistic infections must be maintained when faced with severe HCV recurrence in liver transplant recipients. Moreover, active surveillance against CMV infection and other prophylactic strategies against opportunistic infections should be considered., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Opportunistic pulmonary infections (OPI) represent common life-threatening complications after solid organ transplantation. Our objective was to describe pulmonary infections caused by opportunistic pathogens in solid-organ transplant patients., Methods: We analyzed all adult solid organ recipients (liver, heart, kidney, and pancreas) between July 2003 and June 2010, reporting all episodes of pulmonary opportunistic infection., Results: During the study period, 1656 solid organ transplants were performed and 188 opportunistic infections were diagnosed in 163 patients (incidence 10%). In 40 cases, the site of infection was the lung (21%) with 57.5% occurring between the first and sixth month posttransplantation. The most frequently isolated microorganism was Aspergillus spp (n = 25, 63%), followed by Pneumocystis jirovecii (n = 6 cs, 15%). Twenty-five patients with an opportunistic pulmonary infections died during the follow-up including, 16 related to the infection (40%). The causative organism responsible for the highest mortality was Aspergillus spp (n = 12; 48%). Twenty-one patients with an opportunistic nonrespiratory infection died, five of them related to it (4%). Opportunistic pulmonary infection was associated with an increased mortality rate (P < .001). There was a trend toward a higher mortality among patients who developed OPI during the first 6 months after transplantation., Conclusions: Opportunistic pulmonary infections after solid organ transplantation are not infrequent. The period of risk for developing this infectious complications goes beyond the first 6 months posttransplantation. Mortality due to these infections was high in comparison to that of opportunistic nonrespiratory infections. It is important to keep a high index of suspicion for infectious complications during all posttransplant periods, as this is the first step toward a rapid diagnosis and adequate treatment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Despite recent advances in prevention and treatment, cytomegalovirus (CMV) is still a major complication in transplant patients. This study sought to analyze the incidence of CMV disease and its impact on patient and graft survival., Methods: Between June 2003 and December 2009, we included all kidney, liver, heart, and double transplant patients who underwent solid organ transplantation. They had 1-year posttransplant follow-up., Results: Among the 1427 patients who received kidney (n = 661), liver (n = 494), heart (n = 89), or double (n = 183) transplants, 103 (7.2%) displayed CMV disease. The incidence by type of transplant was: heart (n = 17, 19%), liver (n = 35, 7%), kidney (n = 41, 6.2%), or double transplant (n = 10, 5.5%; P < .001). In 59% of cases, the infection developed during the first 3 months after transplantation. CMV infections ranged from viral syndrome (n = 47, 45%) to tissue-invasive disease (n = 56, 55%), including 38% with gastrointestinal involvement. Relapsing episodes occurred in 12 patients (11%). Discordant donor/recipient CMV serology was present in 151 patients (donor positive/receptor negative), including 34 (22.5%) who developed primary CMV disease (P < .001). Coinfections mostly bacterial, were diagnosed in 38% of patients. An acute rejection episode was present in 31% of patients with CMV disease compared to 20% without this complication (P = .017). Crude mortality was significantly higher among patients with CMV disease (n = 18 patients [18%] vs 92 patients [7%]; P < .001)., Conclusion: Our data confirmed that CMV disease was associated with worse transplant outcomes, with higher incidences of acute rejection episodes and mortality., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Klebsiella pneumoniae is a well recognized source of nosocomial infection in solid-organ transplant (SOT) recipients. It is also the most common species capable of producing extended-spectrum β-lactamases (ESBL). Its treatment can therefore be a challenge owing to antibiotic resistance., Methods: Prospective study of all transplant recipients from July 2003 to December 2007 at our center. Klebsiellla pneumoniae infectious events were recorded., Results: A total of 1,057 patients were enrolled, 509 (48%) renal, 360 (34%) liver, 78 (7%) heart, and 110 (10%) double transplants. We diagnosed 116 episodes of K. pneumoniae infection in 92 patients during the study period, of which 62 were ESBL-producing strains (53%). Thirty-four episodes had bacteremia (29%), 15 of which were caused by ESBL-producing strains. There were no strains of K. pneumoniae producing carbapanemase (KPC). Forty-seven percent of the episodes occurred during the first month after transplantation. The incidence of infection by type of transplant was: renal 11%, liver 7%, cardiac 5%, and double transplant 6% (P=.075). The major sites of infection were urinary tract 72%, surgical wound 5%, intraabdominal 6%, catheter 5%, lung 1%, bloodstream 1%, and others 2%. ESBL-producing K. pneumoniae strains were more common in renal transplant patients (P=.035) and in those who required posttransplant dialysis (P=.022). There were 4 deaths in the first 30 days after the isolation of K. pneumoniae, and 3 of these cases were infections caused by ESBL-producing strains., Conclusions: There was a high incidence of ESBL-producing K. pneumoniae infections in SOT recipients and renal transplant recipients, and those who required dialysis were more likely to develop infection by this strain. No KPC-producing organisms were found in our series. The existence of such a high level of resistance is a well recognized hospital threat, and appropriate policies and interventions should be addressed in high-risk patients., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: Bloodstream infections (BSI) are a major cause of morbidity and mortality after solid organ transplantation. Our aim was to analyze early BSI after solid organ transplantation., Materials and Methods: A prospective cohort study included patients undergoing a kidney, simultaneous kidney-pancreas (SPK), or orthotopic liver transplantation (OLT) from 2003-2007. We prospectively collected demographic variables, underlying chronic diseases, transplantation procedures, and posttransplant complications. Recorded cases of BSI were defined as significant according to CDC criteria. Early BSIs were considered to be those appearing within 30 days posttransplantation., Results: During the study period, we performed 902 transplantations: 474 renal, 340 liver, and 88 pancreas. Seventy episodes of early BSI were diagnosed in 67 patients (7.4%). The incidences of BSI according to the type of transplantation were: 4.8% in renal, 4.5% in SPK, and 12% in OLT (P < .001). Sixty-three percent of the bacteria isolated were gram-negative, the most frequent being Escherichia coli, of which 18 (54%) were extended-spectrum beta-lactamase-producing (ESBL), and Pseudomonas aeruginosa, of which 18 (31%) were multidrug-resistant. The most frequent gram-positive bacteria were coagulase-negative staphylococci (20%). The urinary tract was a frequent source of BSI (27%), followed by a catheter (18%). Two patients (3%) died, both liver recipients, but neither death was related to the BSI., Conclusions: In our setting, the incidence of early BSI among solid organ transplant recipients was high, especially liver recipients, but with low associated mortality. The most frequent sources of infection were urinary tract and catheter. Gram-negative BSI showed a high rate of multidrug resistance.

Background: Mannose-binding lectin (MBL) is a component of the innate immune system that binds the surface of pathogens, activating the complement pathway and acting as opsonin. Certain single-nucleotide polymorphisms of MBL2 are associated with a decrease in the circulating levels of MBL. Our aim was to evaluate the influence of MBL2 polymorphisms in the invasiveness of Cytomegalovirus (CMV) disease after solid organ transplantation., Methods: We include those solid organ transplant recipients who developed CMV disease posttransplant from 2000 to 2006. MBL2 genotyping was performed by sequencing of exon 1 (wild-type allele A and variants B, C, and D) and promoter regions (alleles H and L, X and Y, and P and Q). In the case of liver transplantation, donor MBL2 genotypes were analyzed. Associations were calculated by the chi-square test and binary logistic regression., Results: We included 45 transplant recipients with CMV disease (22 renal, 7 simultaneous kidney-pancreas, 11 liver, and 5 heart), of whom 10 (22%) had invasive CMV disease. No differences were found regarding HH (versus HL or LL), YY and YX (versus XX) and QQ (versus QP and PP) haplotypes with invasive CMV disease (P = 1.000 for all 3 comparisons). Patients with an exon 1 wild-type (AA) haplotype had 36% invasive CMV disease in comparison with 9% of patients with A/O or O/O haplotypes (P = .035). Binary logistic regression analysis showed that patients with exon 1 AA haplotype had an independent risk of developing invasive CMV disease (odds ratio, 6.0; 95% confidence interval, 1.1-32.5)., Conclusions: Our results suggest that exon 1 wild-type genotypes are associated with a higher risk of invasive CMV disease after solid organ transplantation.

Objective: Mycobacterium tuberculosis (TB) is a serious opportunistic infection in solid organ transplant recipients. The TB incidence is 20 to 74 times greater than that among the general population. Our aim was to determine the incidence as well as the clinical, radiological, and microbiological features and outcomes of TB in these patients., Materials and Methods: We reviewed the clinical records of subjects with posttransplant TB from January 1988 to December 2007. A definite TB case was defined by a positive culture; probable TB by a positive smear or histological finding; and disseminated TB when 2 organs were involved. We noted an early diagnosis as ones in the first year posttransplantation. Outcomes were classified following the WHO recommendation and mortality related defined by death during treatment., Results: Among 4634 recipients (2757 kidney, 1334 liver, 361 double kidney-pancreas, and 182 heart), 21 (0.45%) developed posttransplant TB: namely, 0.47%, 0.22%, 1.1%, and 0.54%, respectively. In 2 cases M. tuberculosis did not grow upon culture; the diagnosis was established by positive acid-fast bacilli on a sputum smear or by histological findings on biopsy. The mean posttransplantation time to TB diagnosis was 21 months (48% early TB). Two patients had a previous history of TB. Fever was the most common symptom (71%). Pulmonary tuberculosis represented 47.6% of cases; extrapulmonary, 28.6%; and disseminated, 23.8%. Among the cases of pulmonary TB, 60% had unilateral infiltrates and 10% cavitations on X ray. Eighteen patients completed treatment. Five patients displayed adverse events, 3 of which were liver toxicity. Four patients died, with 3 deaths related to TB., Conclusions: The incidence of TB in this cohort was higher than that among the general population (450 cases/100,000 recipients). TB was associated with adverse effects of treatment and significant mortality.

Background: Cytomegalovirus (CMV) disease is associated with an increased net immunosuppressive state in solid organ transplant recipients, leading to more bacterial and fungal infections. The release of pro- and anti-inflammatory cytokines could be one of the responsible factors., Methods: We prospectively included all patients undergoing solid organ transplantation between April and November 2004. During follow-up, plasma samples were collected in the immediate postsurgical period, at the first and second months, at the time of maximum antigenemia during CMV disease, and at 6 months posttransplantation. We determine the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10. Log-transformed data were compared by a nonparametric Wilcoxon test for related variables., Results: During the study period, we monitored 146 recipients of solid organ transplantation: 77 kidneys, 8 kidney-pancreas, 46 liver, 11 heart, 2 liver-kidney, and 2 heart-kidney. No differences were observed between the TNF-alpha and IL-10 levels in the immediate postsurgical period or during CMV disease. TNF-alpha and IL-10 levels during CMV disease were higher than levels during the first month (mean TNF-alpha first month = 12.71 pg/mL vs CMV disease = 22.71 pg/mL, P = .028; mean IL-10 first month = 3.47 pg/mL vs CMV disease = 19.2 pg/mL, P = .018). Th1/Th2 ratio (measured as TNF-alpha/IL-10) was 1.75 in the immediate postsurgical period, 7.5 during the first month, 1.86 at the time of CMV disease, and 4.61 at the sixth month. The difference in Th1/Th2 ratio during CMV disease and in the first month was statistically significant (P = .043)., Conclusion: During CMV disease, we observed an increase in TNF-alpha and IL-10 release, which was similar to that during the postsurgical period. An imbalance toward an anti-inflammatory pattern was noted in these two periods. This could reflect a cooperative factor increasing the net state of immunosuppression during CMV disease.

Background: With the introduction of prolonged prophylaxis with valganciclovir in cytomegalovirus (CMV) donor/recipient serodiscordance (D+/R-) patients, concerns about a high incidence of late and invasive CMV disease associated with mortality have emerged. We compared the characteristics of CMV disease in D+/R- patients receiving prolonged valganciclovir prophylaxis with R+ patients., Methods: We prospectively followed all solid organ transplant recipients from January 2004 to December 2005. CMV prophylaxis with valganciclovir or ganciclovir was administered as follows: donor- recipient serodiscordance (D+/R-), 12 weeks; induction with antithymocyte globulin or acute rejection episodes requiring steroid pulses, 15 to 30 days; and CMV R+ double kidney-pancreas, 15 days. Transplant characteristics and the development of CMV disease variables were collected for all patients. We defined 2 groups according to the risk of CMV disease: CMV donor/recipient mismatch (D+/R-) and recipient CMV-positive (R+) groups., Results: During the study period we performed 481 solid organ transplantations: 237 kidney, 34 kidney-pancreas, 157 liver, 38 heart, 13 liver-kidney, and 2 heart-kidney. Overall, 36 patients developed CMV disease (7.5%). CMV donor-recipient mismatch (D+/R-) was associated with a greater risk of CMV disease compared with CMV-positive recipients (16% vs 7%; P = .036). Prophylaxis against CMV was longer in the D+/R- group (mean days 73 vs 15; P < .001). CMV disease appeared later in the D+/R- than in R+ group (mean days 123 vs 59; P < .001). We observed a trend toward a lower incidence of tissue-invasive CMV disease among the D+/R- group compared with the R+ group without significance (14% vs 41%; P = .382). Three patients died in the first 30 days after the onset of CMV disease, all of them in the R+ group., Conclusions: In our setting, high-risk patients (D+/R-) receiving prolonged prophylaxis with valganciclovir developed later CMV disease, but this was neither more tissue-invasive nor more life-threatening than in the R+ group.

Introduction: Liver transplant recipients frequently suffer gastrointestinal (GI) complications but their prevalence and their influence on quality of life remain unknown., Objective: The objective of this study was to asses the prevalence, impact on quality of life, and management of GI complications in liver transplant recipients., Patients and Methods: This was an epidemiologic, cross-sectional, multicenter study. Four hundred seventeen liver recipients were recruited in 14 centers. A questionnaire was filled for every patient., Results: The median age of the patients was 55 years. The median time since transplantation was 4.1 +/- 4 years. Whereas 19.2% presented some GI disease before transplantation, 49.4% showed this type of complication after transplantation. Diarrhea was the most prevalent GI complication, and anorexia was the GI disorder that affected patients daily activities the most frequently. GI complications were more frequent among female patients, subjects with pretransplantation hiatal hernia, and those readmitted after transplantation. Of the patients with GI complications, 70.9% received pharmacological treatment (89.7% with gastric protectors). Immunosuppressive therapy was also modified because of GI complications. Immunosuppressive drug dose was reduced in 18.1%, transiently stopped in 3.4%, and definitively stopped in 3.4% of cases. The drug most frequently changed was mycophenolate mofetil: dose reduction, 23.6%; transient withdrawal, 5.7%; and definitive withdrawal, 6.6%., Conclusions: The prevalence of GI complications in the liver transplant population was approximately 50%. GI complications showed a significant impact on the quality of life of the patients. They were related to female gender, to pretransplantation GI pathology, and posttransplantation hospital admission. These complications were frequently managed with pharmacological therapy or with changes in immunosuppressive therapy.

Background: Invasive pulmonary aspergillosis (IPA) remains a major cause of mortality in transplant recipients. New strategies in therapy are needed., Methods: We prospectively followed all solid organ and bone marrow transplant recipients from January 1998 to January 2003 who showed pulmonary infiltrates. We retrospectively analyzed all of the patients diagnosed as having IPA. Clinical and epidemiological data were collected. Influence of new treatment strategies on survival was also analyzed., Results: Thirty-one cases of API were found: 8 definite, 18 probable, 5 possible among recipients of liver (11), bone marrow (9), kidney (7), kidney-pancreas (3), and heart (1) transplants. Five patients (16%) were previously receiving antifungal prophylaxis. The most common symptoms were fever (74%) and dyspnea and dry cough (48%). Six cases (19%) showed dissemination to extrapulmonary sites: central nervous system (CNS) in five and bone in one. The most common radiographic patterns were alveolar infiltrates (58%); the lesions were usually diffuse and bilateral (58%). The most common Aspergillus species identified was A. fumigatus (74%). The test to detect Aspergillus antigen (galactomannan) in serum performed in 13 cases, was positive in eight (61%). The crude mortality rate was 61% (19 of 31), but in patients on mechanical ventilation, it was 94% (OR 88, IC 95%: 7.1-1094), and in patients with CNS involvement, it was 100%. The influence of the different treatment regimens on survival was analyzed in definite and probable cases: Group 1 (12) included patients who received conventional monotherapy and group 2 (12) patients received combination antifungal therapy or liposomal amphotericin B (1-AMB) at high doses. The mortality in group 1 was 83% (10 of 12), and in group 2 it was 42% (5 of 12) (P < 0.05)., Conclusions: The mortality rate of IPA remains high, especially among patients with CNS involvement or those under mechanical ventilation. Combined antifungal therapy or monotherapy with 1-AMB at high doses significantly reduced mortality compared with conventional monotherapy.

The aim of this study was to determine the tacrolimus blood levels in recipients of living donor liver transplants (LDLT) compared with recipients who undergo whole cadaveric liver grafts and to correlate the tacrolimus trough levels with the 12-hour area under the concentration (AUC) curve. From June 2002 to June 2003, the 10 LDLT were prospectively compared with 11 cadaveric transplants. The main immunosuppression was tacrolimus plus steroids. Intraoperative methylprednisolone was administered to all cadaveric organ recipients and only 6 of the 10 LDLT. Median tacrolimus trough levels at day 10 were 14.1 ng/mL for the LDLT group and 9.1 ng/mL for the CLT group (P = NS). The median tacrolimus AUC at day 10 were 185.2 ngxh/mL and 148.1 ngxh/mL for the LDLT group and the cadaveric group, respectively (P = NS). Median tacrolimus trough levels at day 2 were 24.3 ng/mL versus 9.9 ng/mL in the LDLT recipients with and without steroids, respectively (P < .05). Also, median tacrolimus AUC at day 2 were 239 ngxh/mL and 179.7 ngxh/mL when we compared LDLT recipients with and without steroids (P = NS). A significant correlation was observed between tacrolimus trough levels and AUC in the LDLT group (C.C. = 0.936; P < .0001). In conclusion, LDLT recipients display higher tacrolimus blood levels in comparison with cadaveric liver recipients, with a good correlation between tacrolimus trough levels and AUC. Intraoperative steroid administration induces higher tacrolimus levels in LDLT recipients.

Objectives: Our goal was to study a consecutive series of 1000 liver transplants performed in our institution to evaluate the changes over time in donors, recipients, and results., Patients and Methods: With the aim to evaluate differences between transplantation in the first period and the present period, the first consecutive 100 liver transplants performed from June 1988 to June 1990 (first period) were compared with the last consecutive 200 liver transplants performed from January 2001 to June 2003 (second period)., Results: Increased donor age, change in donor cerebral death etiology, and increasing numbers of grafts from alternative methods using cadaveric donors were observed in the second period. Piggy-back technique and the biliary anastomosis without a t-tube was also started in the second period. One-year actuarial patient survival was higher in the second period (84% vs 91.3%). The need for retransplantation in the overall series was 95%. One-, 5-, and 10-year actuarial retransplant survival was 67.7%, 51.3%, and 39.4%, respectively., Conclusions: Technical innovations, better understanding of donor and recipient aspects, and global improvements were the reasons for time-related improved results of liver transplantation.

Background: Bacteremia and septic shock remain important causes of morbidity and mortality after solid-organ transplantation. The aim of this study was to assess the characteristics and risk factors for mortality among patients with bloodstream infections and shock., Methods: From January 1991 to December 2000, all episodes of bloodstream infection were prospectively examined, considering bacteremia or fungemia as significant according to the CDC criteria. Septic shock was diagnosed in a patient with systemic inflammatory response syndrome and persistent dysfunction of at least one organ caused by hypoperfusion despite hemodynamic support., Results: There were 466 episodes of bacteremia in 382 patients, with 66 of them developing septic shock. Risk factors for developing shock were age >50 (P = .006), liver transplant (P = .029), nosocomial infection (P = .034), pulmonary focus (P = .0001), P. aeruginosa infection (P = .001), and polymicrobial etiology (P = .039). On multivariate analysis, only age, nosocomial infection, and pulmonary source were significant. Among 66 shock patients, bacteremia was due to gram-negative bacteria in 53%, gram-positive bacteria in 24%, fungal in 7.5%, and polymicrobial in 12% of patients. The most frequent source was the lung (26%). Empiric antimicrobial therapy was correctly chosen in 79%; however, 36 patients died (54%), including 27 despite correct therapy. Urinary tract infections had less mortality than other foci., Conclusions: Risk factors for developing septic shock in bacteremia were age more than 50 years, nosocomial acquisition, and pulmonary focus. Despite adequate empiric antibiotic therapy, the mortality remained high.