Antifungal Prophylaxis and Treatment Among Lung Transplant Recipients in Early Postoperative Stage: A Single-Center Study

BackgroundLung transplantation remains the only feasible option for certain patients with end-stage lung disease. Lifelong immunosuppression increases the risk of infection, including fungal infections. The aim of this study was to assess the effect of antifungal prophylaxis and treatment among lung transplant recipients in the early postoperative stage.MethodsThis retrospective analysis included 127 patients who underwent lung transplantation between 2014 and 2021 in the lung transplant ward, 65.35% of whom were males. The most common indication for lung transplantation was cystic fibrosis (n = 59; 46.46%). All of the patients were receiving inhaled amphotericin B. Within this group there were patients who also were treated with intravenous caspofungin, intravenous/oral voriconazole, or both.ResultsThe difference in the efficacy against Candida spp. between caspofungin and voriconazole in the early post-transplant period was not statistically significant (χ₂ = 0.5, P = .477). Moreover, the difference in the efficacy against Candida spp. between itraconazole and voriconazole during the first post-transplant year was not statistically significant (χ₂ = 0.46, P = .496).ConclusionCaspofungin and voriconazole are proper and relatively efficient antifungal prophylaxis and treatment options after lung transplantation. There was no significant difference between voriconazole and caspofungin as antifungal agents used in the early post-transplant stage. There was no significant difference between voriconazole and itraconazole as antifungal agents used during the first post-transplant year. Further research on this issue is required.     

Pneumocystis jirovecii Pneumonia in Liver Transplant Recipients: A Systematic Review

BackgroundPneumocystis jirovecii is a fungus that causes pneumonia in immunocompromised patients, such as liver transplant recipients.MethodsWe searched the Medline database in September 2013 for articles referring to infections from P. jirovecii in liver transplant recipients, using the terms “liver transplantation” and “pneumocystis.” Our search yielded 60 articles, 35 of which were used for our review.ResultsP. jirovecii pneumonia (PJP) has an incidence of 1%–11% in liver transplant recipients without prophylaxis and mortality rates of 7%–88%. Most cases occur within the first 7 months after transplantation. When prophylactic treatment with oral trimethoprim-sulfamethoxazole is used, its incidence is only 0%–3%. The duration of its use varies from 3 months to 1 year after the liver transplantation.ConclusionsPJP has relatively high incidence and high mortality rates in liver transplant recipients without prophylactic treatment, which diminishes or even eliminates its occurrence. Therefore, oral trimethoprim-sulfamethoxazole should be used as prophylaxis for 1 year after the liver transplantation in this population.     

High levels of soluble Major Histocompatibility Complex class I related chain A (MICA) are associated with biliary cast syndrome after liver transplantation

BackgroundThe biliary cast syndrome (BCS) is a frequent problem following liver transplantation. The pathogenesis of this complication is not well understood. Previous research has demonstrated that the soluble form of MICA (sMICA) is significantly higher in patients with chronic liver disease and hepatocellular carcinoma (HCC) than in healthy volunteers. The aim of this study is to investigate the possible involvement of sMICA in the formation of BCS after liver transplantation.MethodsSerum soluble MICA was retrospectively evaluated in pre- and post-transplant sera from 133 consecutive primary liver transplant patients and in sera from 88 healthy volunteers using sandwich ELISA. Normal distribution of serum sMICA was described by the data obtained from healthy population and sMICA concentration that was greater than the upper bound 95% normal range was considered as high levels of sMICA. Patient records were reviewed to identify patients who developed BCS.ResultsThe results demonstrated that 37.6% of patients with end-stage liver diseases had significantly higher pre-transplant serum sMICA than in healthy population. 34.4% of recipients with post-transplant high levels of sMICA developed BCS. In contrast, 17.3% of patients with post-transplant normal levels of sMICA developed BCS. The risk of BCS development is significantly associated with the presence of post-transplant high levels of sMICA (P = 0.0365). Further analysis disclosed that patients with decreased post-transplant sMICA following liver transplantation had a lower incidence rate of BCS than those with remained high levels of sMICA after transplantation (10.5% vs. 38.7%, P = 0.0302). Furthermore, log-rank test showed that BCS occurrence was significantly associated with dynamic changes of sMICA among different groups (P = 0.0188).ConclusionsBiliary cast syndrome is more likely to develop in recipients who have post-transplant high levels of sMICA. The data suggested that sMICA might have some immunologic effect on BCS development following liver transplant. Monitoring of serum sMICA could have a prognostic value in assessment of patients with liver transplantation.     

Impact of Tacrolimus Trough Variability on Acute Rejection Following Lung Transplantation

BackgroundAcute rejection is a risk factor for the development of chronic lung allograft dysfunction, the leading cause of morbidity and mortality in lung transplant recipients. Calcineurin inhibitors are the cornerstone of immunosuppression regimens after lung transplantation.MethodsWe retrospectively evaluated the association of tacrolimus level variability with total acute rejection score at 12 months post-transplant. Secondary outcomes included the development of chronic lung allograft dysfunction and antibody-mediated rejection at 24months post-transplant. There were 229 lung transplant recipients included.ResultsThe mean (standard deviation) total rejection score of the cohort was 1.6 (1.7). Patients with high tacrolimus variability at 0 to 3, 3 to 6, and 6 to 12 months on average scored 0.18 (mean 1.6 vs 1.5; 95% CI): -0.3 to 0.66, P =.46), 0.14 (mean 1.7 vs 1.5; 95% CI: -0.32 to 0.6, P = .55), and 0.12 (mean 1.6 vs 1.5; 95% CI: -0.34 to 0.58, P = .62) point higher in 12-month total acute rejection scores, respectively; however, these differences were not statistically significant. The incidences of chronic lung allograft dysfunction and antibody-mediated rejection were numerically greater in the high variability group throughout certain periods; however, this was not consistent throughout all study timeframes and statistical significance was not evaluated.ConclusionsHigh tacrolimus variability was not associated with increased 12-month total acute rejection score. Further studies are needed to assess long-term outcomes with tacrolimus level variability.     

Rapid emergence of a ceftazidime-resistant Burkholderia multivorans strain in a Cystic Fibrosis patient

BackgroundBurkholderia multivorans poses a serious health threat to Cystic Fibrosis patients due to innate resistance to multiple antibiotics and acquisition of resistance to a range of antibiotics due to the frequent use of antibiotics to treat chronic infections. Monitoring antibiotic susceptibility is crucial to managing patient care. We identified the rapid emergence of a ceftazidime-resistant strain in a single patient within four days during a hospitalization for treatment of an exacerbation.MethodsB. multivorans was isolated from expectorated sputum samples using Burkholderia cepacia selective agar. A macrodilution assay was performed on all isolates to determine the minimum inhibitory concentration of ceftazidime. Approximately 4000 colonies were scored to identify the percent of ceftazidime-resistant colonies. Extracted DNA was used to determine the total bacterial counts and abundance of B. multivorans using quantitative PCR.ResultsAn increase from no detectable B. multivorans ceftazidime-resistant colonies to over 75% of all colonies tested occurred within a four-day period. The resistant population remained dominant in 6 of the 8 samples in the following 17 months of the study. qPCR revealed an association between change in the percent of resistant colonies and abundance of B. multivorans, but not of total bacteria. No association was found between the acquisition of resistance to ceftazidime and other antibiotics commonly used to treat B. multivorans infections.ConclusionsThe rapid emergence of a ceftazidime-resistant by B. multivorans strain occurred during a hospitalization while under selective pressure of antibiotics. The resistant strain maintained dominance in the B. multivorans population which resulted in an overall decline in a patient health and treatment efficacy.     

Post-Transplantation Anemia and Risk of Death Following Lung Transplantation

BackgroundPost-transplantation anemia (PTA) is frequent among solid organ transplant recipients and has been associated with increased morbidity and mortality. However, the prevalence and impact of PTA in lung transplant recipients is still not elucidated.MethodsWe performed a retrospective cohort study of adult Danish lung transplant recipients between January 2010 and December 2019. The prevalence and severity of PTA were determined during the first three years post-transplantation. Associations between PTA and selected risk factors were established using uni- and multivariate logistic regression models.ResultsA total of 278 patients were included. At one and three years post–lung transplantation the prevalence of PTA was 75% and 52%, respectively. Male sex was associated with increased odds of PTA at all time points (aOR ranging from 2.3, 95% CI 1.1-4.6, P = 0.02 to 5.9, 95% CI 2.6-14, P < .001). Cystic fibrosis was also associated with anemia at one-year post-transplantation (aOR 4.3, 95% CI 1.2-17, P = 0.03). We found no strong associations between PTA and renal function or viral infections. Excess mortality in recipients with moderate or severe anemia compared to patients with mild or no anemia was borderline statistically significant at one-year post-lung transplantation (aHR 2.0, 95% CI 0.9-4.4, P = 0.07).DiscussionPost-transplantation anemia is very common in Danish lung transplant recipients. Male sex and cystic fibrosis are independent risk factors for development of anemia. Further investigation on PTA, the underlying mechanisms, and its clinical impact is needed.     

Post-transplant eosinophilic gastrointestinal disorders and lymphoproliferative disorder in pediatric liver transplant recipients on tacrolimus

AimTo examine and characterize post-transplant eosinophilic gastrointestinal disorders (PTEGID) and post-transplant lymphoproliferative disorder (PTLD) in pediatric liver transplant recipients.MethodsThis is a single center retrospective study of all liver transplant recipients aged 0–18 years from 1999 to 2019 who received tacrolimus as their primary immunosuppressant. Demographic data and clinical/laboratory data including PTEGID, PTLD, liver transplant types, Epstein-Barr virus status, and blood eosinophil count were reviewed. Analysis was done with logistic regression and Mann-Whitney U test.ResultsNinety-eight pediatric liver transplant recipients were included with median age at transplantation of 3.3 years (IQR: 1.1–9.3). The major indication for transplantation was biliary atresia, 51 (52%) cases. Eight (8%) children had PTLD and 14 (14%) had PTEGID. Receiving liver transplantation at an age of ≤1 year was associated with developing PTEGID (OR = 11.9, 95% CI = 3.5–45.6, p < 0.001). Additionally, eosinophilic count of ≥500/μL was associated with having PTLD (OR = 10.7, 95% CI = 1.8–206.0, p = 0.030) as well as having at least one liver rejection (OR = 2.8, 95% CI = 1.2–7.0, p = 0.024). The frequency of food-induced anaphylaxis significantly increased post-transplantation (p = 0.023).ConclusionsPTEGID and PTLD are common in this cohort and are associated with certain risk factors that help screen children to improve recipient survival. Further studies are needed to evaluate the clinical benefits of these findings.     

Recurrent Clostridium difficile colitis in cystic fibrosis: An emerging problem

ObjectiveTo examine the incidence of recurrent Clostridium difficile infection in patients with cystic fibrosis (CF), including patients who had undergone lung transplantation, and review clinical findings in hospitalized patients with C. difficile colitis.MethodsA retrospective chart review was performed to examine the clinical presentation and management of patients with cystic fibrosis (CF) who received care at the University of Wisconsin Hospital and Clinics (UWHC) from 1994 to 2011 and were prospectively identified with C. difficile colitis.ResultsTen cases of C. difficile associated disease (CDAD) occurred in patients with CF followed by our Adult CF Center over a period of 17 years, and 4 patients were bilateral lung transplant recipients. Two of the lung transplant recipients had recurrent CDAD that lead to fulminant pancolitis, surgical intervention, and shock. Two patients in the non-transplant group experienced recurrent C. difficile infection that led to fulminant pancolitis with associated systemic inflammatory response syndrome and required colectomy.ConclusionsC. difficile colitis can cause life threatening illness in patients with CF, and symptoms may be subtle and/or atypical and lead to significant delay in diagnosis. Patients with recurrent C. difficile colitis are at high risk of fatal outcome, and empiric therapy should be considered for patients with previous C. difficile colitis even in the absence of disease when broad-spectrum antibiotics are given to treat bacterial infection.     

Liver transplantation without isoniazid prophylaxis for recipients with a history of tuberculosis

Abstract:  Tuberculosis remains one of the most serious infections after organ transplantation. Isoniazid prophylaxis for liver transplant recipients with a history of tuberculosis is generally recommended. However, its benefit is controversial because of potential hepatotoxicity of isoniazid. It is crucial to determine appropriate post-transplant managements for the recipients with a history of tuberculosis. The purpose of this study was to investigate the necessity of isoniazid prophylaxis for liver transplant recipients who had a history of tuberculosis. The medical records of 1116 liver transplant recipients were studied, of whom seven had a history of tuberculosis (0.63%). One who underwent living-donor liver transplantation for fulminant hepatic failure was excluded from evaluation because of early death, caused by bacterial sepsis two months after transplantation, although reactivation of tuberculosis was not observed. The median observation period after transplantation was 25.5 months (range 12–82). Reactivation of tuberculosis did not occur in any of these six patients. In conclusion, we could not find rationale for isoniazid prophylaxis in liver transplant recipients with past diagnosis of tuberculosis, when the disease is considered to be inactive. Tuberculosis should be considered as cause of post-transplant infections, and careful post-transplant observations are essential for an early diagnosis.     

Impact of Donor-Derived Multi-drug–Resistant Organism Infections on Abdominal Solid Organ Transplantation Recipients in China

BackgroundInfection with multi-drug–resistant organisms (MDROs) is a life-threatening disease among abdominal solid organ transplantation recipients. Reports of donor-derived (DD) MDRO infections were few, but adverse clinical outcomes were severe, such as death or graft loss.MethodsThe medical records of 68 donation after citizens’ death donors with MDRO infections and 20 recipients transmitted with infections between October 1, 2015, and September 1, 2020, were reviewed according to the Declaration of Helsinki and the Declaration of Istanbul. There were no grafts from prisoners, and no donors were not coerced or paid.ResultsPrevalence and mortality of DD-MDRO infection among abdominal solid organ transplantation recipients were 2.3% and 18.1%, respectively. The prevalence rate of DD-MDR gram-negative bacterial infection was higher than that of gram-positive bacterial infection (1.7% vs 0.6%). Negative culture of specimens occurred in 9 of 68 donors. Recipients with DD-MDR gram-negative bacterial infections had a significantly lower survival rate compared with DD-MDR gram-positive bacterial infections (P = .046).ConclusionsDonation after citizens’ death donors and recipients had high MDRO infection rates, and gram-negative bacteria were the predominant pathogens. When a possible DD-MDRO infection occurs, there may be adverse outcomes with limited choice of antibiotics. A nationwide surveillance and communication network needs to be established in China.     

Vitamin D deficiency is common in kidney transplant recipients,but is not associated with infections after transplantation

The relevance of vitamin D for infections after kidney transplantation is poorly defined. 25-OH vitamin D (25-OHD) levels of 135 kidney transplant recipients, enrolled in the Swiss Transplant Cohort Study, were determined peri-transplant and 6 months post-transplant. Logistic regression was used to address the associations of 25-OHD and overall infections and bacterial infections, respectively. For the first 6 months post-transplant, 25-OHD peri-transplant, and for the second period (after 6 to 30 months post-transplant), 25-OHD at 6 months post-transplant was considered. Vitamin D deficiency was common peri-transplant and remained highly prevalent 6 months after transplantation despite frequent supplementation. Median 25-OHD levels increased from 12.0 ng/mL (IQR 5.3-19.5) peri-transplant to 16.5 ng/mL (IQR 10.6-22.6) 6 months post-transplant (P = .005). We did not detect a significant association between 25-OHD and overall infections (adjusted odds ratio (aOR) 1.05, 95% confidence interval (95%CI) 0.44-2.51; aOR 0.67, 95%CI 0.31-1.43) or bacterial infections (aOR 0.79, 95%CI 0.32-1.96; aOR 0.79, 95%CI 0.35-1.75) for the first and second period. To conclude, at both time points, vitamin D deficiency was observed in more than 50% of kidney recipients, albeit an increase in 25-OHD in the longitudinal course was observed. No significant association between 25-OHD and infections was detected.     

Positive Microbiological Cultures in the Respiratory Tract of High Model for End-Stage Liver Disease (MELD) Liver Transplant Recipients With and Without Pneumonia

BackgroundPneumonia in liver transplant recipients is one of the most common infections in the early phase after transplantation. The diagnosis is based on clinical signs combined with positive microbiological samples taken from the lower respiratory tract. However, the role of bacterial colonization is not clear, nor is its association with pneumonia or its long-term consequences. The aim of this study was to investigate the association between positive microbiological findings and clinically relevant pneumonia and analyze different clinical and laboratory parameters for their association with pneumonia in liver transplant recipients.MethodsThis was a retrospective analysis of 266 adult orthotopic liver transplantations between January 2008 and December 2013. A multidisciplinary in-house specialist panel established and confirmed the diagnosis of clinically relevant pneumonia in microbiologically positive patients.ResultsOf the 266 transplantations analyzed, 54 patients (20%) showed microbiologically positive trachea-bronchial cultures during the first 21 days after liver transplantation. Of those 54 patients, 24 (44.4%) had pneumonia as rated by the multidisciplinary specialist panel. Presence of gram-negative Enterobacteriaceae (P = .013) and positive chest radiologic findings (P = .035) were associated with pneumonia in microbiological-positive patients. Although patients with pneumonia had the lowest long-term survival, those without pneumonia but with positive microbiological cultures had still worse survival compared with the Model for End-Stage Liver Disease–matched control group without positive cultures (P = .012).ConclusionsGram-negative Enterobacteriaceae and positive radiologic findings were associated with pneumonia in liver transplant recipients with positive microbiological trachea-bronchial cultures. Recipients with bacterial colonization without pneumonia also showed decreased long-term survival.     

Sepsis is associated with lack of monocyte HLA-DR expression recovery without modulating T-cell reconstitution after lung transplantation

BackgroundImmunosuppressive strategy targets mainly adaptive immunity after solid organ transplantation. We assessed the influence of early post-operative sepsis on T cell and monocyte reconstitution in anti-thymocyte globulin (ATG)-treated lung transplant recipients.MethodsWe retrospectively included recipients who underwent a first lung transplant at our Lung Transplant Center (Marseille, France) between July 2011 and February 2013. Peripheral blood T-lymphocyte subset counts and monocyte HLA-DR (mHLA-DR) expression routinely performed by flow cytometry within 60 days post-transplant were analyzed. We compared the immune kinetics of patients who did or did not develop sepsis during the post-operative intensive care unit stay.ResultsAmong the 37 recipients included, 19 patients (51%) developed at least one episode of sepsis. At the ICU admission, septic recipients had higher SOFA score (9 [7.5–9] versus 6 [[4], [5], [6], [7]]), p = .01), higher primary graft dysfunction score (1.4 ± 1.4 versus 0.3 ± 0.7, p = .008) and more frequent use of ECMO (47% versus 0%, p = .003). Whereas both groups had similar T-lymphocytes reconstitution in the post-operative period, mHLA-DR reconstitution was dramatically affected in septic patients after day 14, median mHLA-DR expression at 2.3 MFI [1.3–3.5] in the septic versus 8.0 MFI [5.1–10.5] in the non-septic group, p = .02.ConclusionWe found that sepsis is negatively correlated with the mHLA-DR expression but not adaptive T cell immune reconstitution. This finding highlights the importance of immunomonitoring after lung transplantation and questions the strategy of a lower immunosuppression therapy in context of sepsis.     

Correlation analysis of the peripheral blood lymphocyte count and occurrence of pneumonia after lung transplantation

BackgroundInfections are the most common complication in patients after lung transplantation and the main cause of death at all stages after transplantation; therefore, awareness regarding the occurrence of infectious pneumonia after lung transplantation is vital. This study aimed to explore the correlation between the absolute lymphocyte and T-lymphocyte subpopulation counts in the peripheral blood and the occurrence of pneumonia after lung transplantation and to predict the risk of pneumonia development after lung transplantation.MaterialsPatients who underwent lung transplantation with long-term follow-up between June 2018 and December 2021 were prospectively included. The patients were divided into pneumonia and non-pneumonia groups. Demographic and clinical characteristics, and the levels of leukocytes, neutrophils, platelets, C-reactive protein (CRP), procalcitonin (PCT), serum albumin, peripheral blood T lymphocytes, and CD4+ and CD8+ T cells in the peripheral blood were measured in both groups.ResultsWe included 22 patients with post-lung transplants in the analysis. Of the 104 collected samples, 26 (56.5%) were pathogenically positive, 16 (61.5%) had bacterial infections, 7 samples (26.9%) had fungal infections, and 8 (30.8%) had viral infections. Patients with pneumonia had higher levels of peripheral blood neutrophils (P = 0.01), platelets (P = 0.03), and CRP (P < 0.001) than did those without pneumonia. Logistic regression analysis showed that the levels of peripheral blood neutrophils, total T lymphocytes, CRP, and PCT were associated with the development of pneumonia after transplantation (P < 0.05), as documented by their area under the curve (AUC) values of 0.702, 0.792, 0.899, and 0.789, respectively. The AUC for the combined receiver operating characteristic curve for predicting the development of pneumonia was 0.943, with a sensitivity of 91.3% and specificity of 93.1%. There was no significant difference in T-lymphocyte counts in patients with lung transplants between the pneumonia and non-pneumonia groups who were treated with two anti-rejection agents. In contrast, the absolute lymphocyte, total T-lymphocyte, and CD4+ and CD8+ T-cell counts in patients who developed pneumonia after treatment with three anti-rejection agents were lower than those in patients who did not develop pneumonia (P < 0.05).ConclusionBacterial pneumonia is more common after lung transplantation than after fungal or viral infections. Peripheral blood T-lymphocyte counts combined with neutrophil, CRP, and PCT levels had good predictive value for the development of pneumonia after lung transplantation. Monitoring of patients should be strengthened by implementing peripheral blood T-lymphocyte counts to improve the early identification and prevention of pneumonia after lung transplantation.     

Immune reconstitution syndrome-like entity in lung transplant recipients with invasive aspergillosis

BackgroundIncidence, characteristics, and risk-factors for invasive aspergillosis (IA)-associated immune reconstitution syndrome (IRS) in lung transplant recipients are not known.MethodsPatients comprised 68 lung transplant recipients with proven/probable IA followed for 12 months. IRS was defined based on previously proposed criteria.ResultsIn all, 7.3% (5/68) of the patients developed IRS based on aforementioned criteria, a median of 56 days after initiation of antifungal therapy. This entity was associated with heart–lung transplantation (p = 0.006), anti T-cell agent use (p = 0.003), discontinuation of calcineurin inhibitor agent (p = 0.002), and disseminated IA (p = 0.069). In a risk assessment model, IRS developed in 0% (0/55) of the patients with none of the aforementioned factors, 28.6% (2/7) with one, 33.3% (1/3) with two, and in 1/1 patient with 3 factors (X² for trend p = 0.0001). Three out of 5 patients with IRS died and 2 of 3 deaths in this group were due to chronic rejection.ConclusionsOverall 7% of the lung transplant recipients with IA appear to develop an IRS-like entity. Clinically assessable factors can identify patients at risk for post-transplant IA-associated IRS. Deaths due to chronic rejection were significantly higher in patients with IRS than those without IRS.     

Evolution of Anxious-Depressive Symptomatology in Liver and Kidney Transplant Recipients: Hospitalization and 12-Month Post-Transplantation Phases

ObjectiveThe objective of this study was to compare the evolution (hospitalization in the transplantation unit and at 12 months post-transplantation) of anxious and depressive symptomatology in cadaveric transplant recipients as a function of type of organ implanted (liver or kidney).MethodsUsing a 2 × 2 mixed factorial design, 2 groups were selected: 34 liver transplant recipients and 41 kidney transplant recipients. Both groups were assessed in 2 phases: (1) in the transplantation unit after discharge from the intensive care unit; and (2) 12 months after discharge from the hospital following implantation surgery. The Hospital Anxiety and Depression Scale and the Scale for the Assessment of Social Support were administered. A mixed analysis of covariance was used to assess the influence on transplant recipients' anxious-depressive symptomatology of 2 independent factors: phase (hospitalization in the transplantation unit and at 12 months post-transplantation) and organ (liver and kidney). Perceived social support and age were included as covariates in the analyses. We also calculated d and w as effect size indexes.ResultsInteractive effects of the factors phase and organ were found in the variable anxiety (P = .005). Specifically, the following simple effects were significant: (1) kidney transplant recipients presented more anxious symptomatology while hospitalized in the transplantation unit than at 12 months post-transplantation (P = .001; d = 0.52; medium effect size); and (2) kidney transplant recipients presented more anxious symptomatology than liver transplant recipients while hospitalized in the transplantation unit (P = .013; d = ?0.59; medium effect size). No statistically significant effect was obtained for the variable depression.ConclusionWorse mental health (anxious symptoms) was associated with kidney transplant recipients but not with liver recipients while recovering from the implantation surgery in the transplantation unit.     

Opportunistic Infections After Induction With Alemtuzumab or Basiliximab: A 3-Year Kidney Transplantation Experience

BackgroundAntibody induction immunosuppression is commonly used in kidney transplantation to decrease the risk of early acute rejection. However, infectious complications may arise in patients treated with higher intensity induction immunosuppression. In this study, we compared the rate of opportunistic infections during the 3 years after kidney transplantation in recipients who received either alemtuzumab or basiliximab for induction therapy.MethodsAll renal transplant recipients from our center who received induction with alemtuzumab between 2011 and 2016 were included and matched 1:2 (by age and date of transplant) to renal transplant recipients who received basiliximab. The primary outcome was the rate of opportunistic infections.ResultsTwenty-seven patients received alemtuzumab (mean age = 50.8 years; SD ±12), and 54 received basiliximab (mean age = 50.8 years; SD ±11.8). Infections within 3 years posttransplant were not different between groups: BK viremia (P = .99), BK nephritis (P = .48), cytomegalovirus infection (P = .13), varicella zoster virus (P = .22), and all infections (P = .87). Time to infection (P = .67), patient survival (P = .21), and time to rejection (P = .098) were similar in both groups. There were also no group differences in delayed graft function (P = .76), graft loss (P = .97), or rejection (P = .2).ConclusionThe rate of infection was not significantly increased in recipients receiving lymphocyte-depleting alemtuzumab compared to recipients receiving basiliximab induction therapy, despite receiving similar maintenance immunosuppression. Although the immunologic risks differed between the 2 groups, there was no observable difference in clinical outcomes.     

Sex- and age-based comparison of serum immunoglobulins following liver transplantation

BackgroundOver a quarter of organ transplant recipients have low immunoglobulin levels in their early post-transplant course, which is associated with increased risk of infection and mortality. Although immunoglobulin level varies by sex among healthy individuals, it is unknown how such differences are affected by transplant-related immunosuppression. This study compared post-liver transplant immunoglobulin G (IgG) between sexes at varying ages.MethodsSerum specimens from a prospective cohort of 130 liver transplant recipients were analyzed. IgG was measured at time of transplant and from one-month post-transplant samples. Post-transplant IgG was compared between sexes using multivariable linear regression. Four age and sex categories were created (women<50, women≥50, men<50, men≥50) and the model repeated with this as the explanatory variable. The relationship between sex hormone concentrations and post-transplant IgG was also explored. Infection type and incidence were examined within groups.ResultsThe cohort included 99 men, 31 women (mean age 53). In adjusted linear regression, post-transplant IgG was not significantly different by sex (p = 0.92). However, when broken into four categories by age and sex, the contrast in IgG levels between younger versus older patients was strikingly greater among women than among men. An interaction term including age and sex was statistically significant (p = 0.03). The combined age-sex categorical variable was also significantly associated with post-transplant IgG (p = 0.01). Finally, an association was identified between baseline estradiol level and post-transplant change in IgG (p = 0.04).ConclusionsSex and age have an important relationship with post-transplant IgG with older women demonstrating lowest concentrations. Immunoglobulin levels have previously demonstrated association with post-transplant outcomes.     

Antibiotic Prophylaxis at Urinary Catheter Removal Prevents Urinary Tract Infection After Kidney Transplantation

BackgroundUrinary tract infections (UTI) are common nosocomial infections in kidney transplant recipients, with limited evidence to guide antibiotic prophylaxis at urinary catheter removal. The aim of our study was to evaluate the effect of short-term antibiotic therapy at the moment of catheter removal after kidney transplantation.MethodsTwenty kidney transplant recipients received 250 mg of ciprofloxacin orally twice daily 1 day before and at the day of the removal of the urinary catheter and were compared with 20 kidney transplant recipients without prophylaxis. UTI was diagnosed by use of urine culture and clinical signs.ResultsAll patients were comparable in sex, age, etiology of end-stage renal failure, immunosuppression, donor type, and initial function. After catheter removal at the 6th postoperative day, a rapid rise of UTI in kidney transplant recipients without prophylaxis (n = 12, 60%) was observed, whereas in patients with antibiotic prophylaxis the rate of UTI could be significantly reduced to 20%. Escherichia coli was the most isolated pathogen in the patients with UTI and was detected at the catheter tip in more than 50% of cases. In 2 patients (10%) after antibiotic prophylaxis, a ciprofloxacin-resistant E coli strain was detected.ConclusionsThe use of antibiotic prophylaxis during urinary catheter removal is recommended to prevent UTI in kidney transplant recipients.     

Gut microbiota intervention by pre and probiotics can induce regulatory T cells and reduce the risk of severe acute GVHD following allogeneic hematopoietic stem cell transplantation

BackgroundAcute graft-versus-host disease (aGVHD) is one of the leading causes of limitation and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Numerous studies have shown that changes in the gut microbiome diversity increased post-transplant problems, including the occurrence of aGVHD. Probiotics and prebiotics can reconstitute the gut microbiota and thus increase bacterial metabolites such as short-chain fatty acids (SCFAs) that have immunomodulatory effects preventing aGVHD in recipients of allo-HSCTs.Methods/Study DesignWe conducted a pilot randomized clinical trial to investigate whether oral synbiotics are associated with the prevention or reduction in occurrence/severity and mitigate complications of aGVHD following allo-HSCT. A commercially available synbiotic mixture containing high levels of 7 safe bacterial strains plus fructo-oligosaccharides as a prebiotic was administered to allo-HSCT recipients. Out of 40 allo-HSCT patients, 20 received daily a synbiotic 21 days prior to transplantation (days −21 to day 0). In contrast, in the control group 20 recipients of allo-HSCT did not receive a symbiotic therapy.ResultsWithin first 100 days of observation, the incidence of severe (grade III/IV) aGVHD in the a synbiotic-therapy group was 0% (0 out of 20 patients), whereas it was 25% (5 out of 20 patients) in the control group (P = 0.047). The median percentage of CD4 + CD25 + Foxp3+ regulatory T cells (Tregs) among CD4+ lymphocytes on day 28 after HSCT in the synbiotic group was higher (2.54%) than in control group (1.73%; P = 0.01). There was no difference in Treg cells on day 7 after HSCT between two groups. However, the median percentage and the absolute count of Tregs in patients who experience aGVHD was significantly lower on days 7 and 28 after HSCT (both P < 0.05). The overall 12-month survival (OS) rate was higher (90%) in the symbiotic-treated patients than in the control group (75%), but the difference was not statistically significant (P = 0.234).ConclusionOur preliminary findings suggest that synbiotic intake before and during the conditioning regimen of allo-HSCT patients may lead to a reduction in the incidence and severity of aGVHD through the induction of CD4 + CD25 + Foxp3+ regulatory T cells, thus contributing to the improvement of transplant outcomes. Much larger studies are needed to confirm our observations.