Pediatric Liver Transplant Patients Research Articles

Approval of Mycophenolate Mofetil for Prophylaxis of Organ Rejection in Pediatric Recipients of Heart or Liver Transplants: A Regulatory Perspective.

On June 6, 2022, the FDA expanded the indications for mycophenolate mofetil (MMF) to include the prophylaxis of organ rejection in combination with other immunosuppressants in pediatric recipients of allogeneic heart or liver transplants aged 3 months and older. The approved oral dosing regimen for these patients was a starting dose of 600 mg/m2 with titration up to a maximum of 900 mg/m2 twice daily. Data to support efficacy in pediatric patients were derived from established pharmacokinetic (PK) relationships across approved populations, a PK study in pediatric liver transplant recipients, and information from the Scientific Registry of Transplant Recipients database. Information supporting safety was based on comparing mycophenolic acid (MPA) exposure with that in pediatric kidney transplant recipients, the published literature, and post-marketing safety reports. Efficacy in pediatric patients was established based on extrapolation of efficacy from studies in adult liver, adult heart, and pediatric kidney transplant populations, and similarity in MPA exposure between pediatric and adult patients. Review of the data supported an oral dosing regimen for pediatric heart transplant and liver transplant recipients consisting of a starting dose of 600 mg/m2 up to a maximum of 900 mg/m2 b.i.d. A dosage range for MMF is recommended recognizing that the MMF dose may be modified in clinical practice for myriad factors. The dosage recommendations in the labeling for pediatric liver and pediatric heart transplant patients are intended to permit individualized dosing based on clinical assessment of these factors.

Biliary strictures post pediatric liver transplantation-incidence and risk factors in a single tertiary referral transplant center.

Biliary strictures are a significant cause of morbidity and graft loss in pediatric liver transplant recipients. Risk factors for the development of biliary strictures are not fully established. We aimed to evaluate the incidence of biliary strictures and treatment modalities outcomes and to identify potential risk factors for occurrence. Pediatric patients who underwent liver transplantation in the single tertiary pediatric liver transplant center in Israel were evaluated. We compared demographics, presentation, laboratory results, imaging, treatment, and outcomes between patients with and without biliary stricture. Multivariate regression analyses were used to identify risk factors for biliary strictures. Among 121 pediatric liver transplant patients, 65 (53.7%) were males; the median age at the time of liver transplantation was 43 (3-215) months. Fifteen patients (12.4%) had biliary strictures following transplantation. One (7%) patient with biliary stricture was treated via endoscopic retrograde cholangiopancreatography, and 12 patients (80%) underwent interventions via a percutaneous transhepatic approach. Nine of the 12 patients were treated successfully, requiring one or multiple procedures, while the remaining had surgery or laser therapy. Risk factors for the development of biliary strictures were biliary leak, acute cellular rejection, and the presence of two biliary anastomoses. In our cohort, the presence of two biliary anastomoses and post-transplant complications including acute cellular rejection and early biliary leaks were associated with biliary strictures in pediatric liver transplantation recipients. Percutaneous transhepatic interventions result in good outcomes in most patients.

Incidence, causative organisms, and risk factors of bloodstream infections in pediatric liver transplant patients: a systematic review.

Bacterial bloodstream infections (BSI) are the leading cause of mortality and morbidity in pediatric solid organ transplant recipients. This systematic review aimed to pool global data from leading transplant institutions and identify the overall incidence, risk factors, and causative organisms of BSI in pediatric liver transplant recipients. A systematic review of the PubMed and OVID databases was conducted from 2000 to 2022. The initial search yielded 252 unique articles, which were independently reviewed by 2 authors. Articles that reported pediatric-specific data on BSI in isolated liver transplant patients were included, including the incidence of BSI, isolated organisms, and involved risk factors involved. This systematic review was registered with PROSPERO (ID: CRD42023403206). Fourteen articles from the United States, France, Iran, Japan, Korea, South Africa, Thailand, and Turkey were included. A total of 4,812 liver transplants were included in the final analysis. The mean patient age was 25 months (age range, 0-18 years), and 50.9% were male. The overall incidence of BSI was 23.5% (range, 14.7%-55%). The most commonly reported organisms were Staphylococcus epidermidis, Enterococcus, Klebsiella spp., and Escherichia coli. Among the risk factors studied, postoperative biliary complications, a medical history of biliary atresia, and younger age were the risk factors most commonly associated with BSI. Bacterial BSI after pediatric liver transplantation occur at a high incidence, with a unique organism profile notable for a higher percentage of gram-negative organisms. Further studies are required to determine the most appropriate prophylactic and empirical antibiotic management strategies for this population.

Infectious complications in pediatric patients after liver transplantation in the first 3 months at the Fundación Valle del Lili, a Latin American transplant center.

IntroductionIn pediatric patients undergoing liver transplantation, infections are one of the primary complications. The etiology varies depending on the time elapsed post-transplant, with early presentations of bacterial and fungal infections, followed by viral and parasitic infections. There is limited literature describing the prevalence of infectious complications in this group of patients in Colombia. ObjectiveTo describe infectious complications in patients undergoing liver transplantation within the first 3 months post-procedure at the Fundación Valle del Lili, Cali, Colombia. MethodsA case series of 165 pediatric liver transplant patients during the period 2011-2017. A descriptive analysis of all entered data was conducted. Survival analysis using the Kaplan-Meier method was performed, with an exploratory analysis comparing patient survival based on the presence of infection, censored for death related to postoperative complications. ResultsThe primary diagnosis at the time of transplantation was biliary atresia in 65% of cases. A total of 215 infectious episodes were recorded in 92 pediatric liver transplants. The most frequent microorganisms were Klebsiella pneumoniae (21%), Cytomegalovirus (CMV) (7%), Pseudomonas aeruginosa (7%), Escherichia coli (6%), and Epstein Barr Virus (EBV) (6%). Three-month patient survival was 92% for infection-related mortality. DiscussionInfectious complications within the first three months post-pediatric liver transplantation were predominantly bacterial in origin. Bacterial and fungal infections manifested earlier, while viral infections appeared later. Infectious complications did not impact the three-month patient survival in this group.

Utilization of older deceased donors for pediatric liver transplant may negatively impact long-term survival.

Multiple adult studies have investigated the role of older donors (ODs) in expanding the donor pool. However, the impact of donor age on pediatric liver transplantation (LT)has not been fully elucidated. UNOS database was used to identify pediatric (≤18 years) LTs performed in the United States during 2002-22. Donors ≥40 years at donation were classified as older donors (ODs). Propensity analysis was performed with 1:1 matching for potentially confounding variables. A total of 10,024 pediatric liver transplantation (PLT) patients met inclusion criteria; 669 received liver grafts from ODs. Candidates receiving OD liver grafts were more likely to be transplanted for acute liver failure, have higher Model End-Stage Liver Disease/Pediatric End-Stage Liver Disease (MELD/PELD) scores at LT, listed as Status 1/1A at LT, and be in the intensive care unit(ICU) at time of LT (all p < 0.001). Kaplan-Meier (KM) analyses showed that recipients of OD grafts had worse patient and graft survival (p < 0.001)compared to recipients of younger donor (YD)grafts. KM analyses performed on candidates matched for acuity at LT revealed inferior patient and graft survival in recipients of deceased donor grafts (p < 0.001), but not living donor grafts (p > 0.1)from ODs. Cox regression analysis demonstrated that living donor LT, diagnosis of biliary atresia and first liver transplant were favorable predictors of recipient outcomes, whereas ICU stay before LT and transplantation during 2002-12 were unfavorable. Livers from ODs were used for candidates with higher acuity. Pediatric recipients of livers from ODs had worse outcome compared to YDs; however, living donor LT from ODs had the least negative impact on recipient outcomes.

2725. Bacterial blood stream infections in Pediatric Liver Transplant Patients: Prevalence, Organisms and Risk factors. A Systematic review

Abstract Background Bacterial blood stream infection (BSI) is a leading cause for mortality and morbidity in the pediatric solid organ transplant recipient population. This systematic review aims at pooling global data from the leading transplant institutions to identify the overall prevalence and risk factors associated with bacterial BSI and the most common causative organisms. Methods A systematic review of PubMed and OVID databases was conducted for the past 20 years. Initial search from both databases had a yield of 252 unique articles which were reviewed independently by two authors. Data related to demographics, prevalence, organisms and risk factors were extracted from the articles and subsequently analysed. The systematic review was registered on PROSPERO (ID: CRD42023403206). The PRISMA flow diagram visually summarises the screening process Results A total of 14 articles were included from the United States of America, France, Italy, Thailand, Japan, Spain and Korea. A total of 4215 liver transplants were included in the final analysis. The overall prevalence of BSI in pediatric liver transplant patients was 23.5% with the highest prevalence reported in Japan (39.5%) and lowest in the USA (18.7%). Mean age of the patients was 25 months and 54% were females. The most common organisms reported were Staphylococcus epidermidis at 22.8% followed by Enterococcus species (16.6%), Klebsiella species (11.9%) and Escherichia coli (11.4%). Among the risk factors studied, postoperative biliary complications, past medical history of biliary atresia and younger age were the risk factors most associated with BSI. Prevalence of bloodstream infections (BSI) post pediatric liver transplant in included countries. Bacterial organisms isolated in blood cultures in pediatric post liver transplant patient with a bloodstream infection. Conclusion Bacterial BSI post pediatric liver transplantation occurs with high prevalence. Further studies need to be conducted to better define risk factors for BSI and determine the best empirical antibiotic management for BSI in this population as the distribution of organisms varies greatly from otherwise healthy pediatric patients. Disclosures All Authors: No reported disclosures

Liver transplantation for pediatric patients with congenital heart disease: A single-center study in mainland China.

Liver transplantation (LT) is a serious cardiovascular stressor for patients with end-stage liver disease (ESLD). Data on the effects of cardiovascular diseases on pediatric LT is limited. No study on LT for pediatric patients with ESLD combined with congenital heart disease (CHD) has been reported from mainland China. A total of 1005 patients were included in this study. The Kaplan-Meier method with log-rank testing was used to evaluate survival outcomes between groups. Univariable and multivariable Cox regression models were used to determine the risk factors for patient and graft survival. The most common indication for LT was biliary atresia (BA 90.3%). The prevalence of CHD was 3.8% (38). 42 CHD were found in 38 patients. The incidence of death and graft loss was more common in the CHD group than in the no-CHD group (13.2% vs. 5.0%, p = .045 and 15.8% vs. 6.2%, p = .019, respectively). The 5-year patient survival and graft survival in the CHD group versus the no-CHD group was 86.8% versus 94.7% (log-rank p = .022) and 84.2% versus 93.5% (log-rank p = .015), respectively. No significant differences were observed in re-transplantation, hepatic artery thrombosis (HAT), and portal vein thrombosis (PVT). After adjusting for age, BMI, etiology of LT, and other confounding factors, we can still find that the presence of CHD was associated with patient and graft survival after LT. The presence of CHD was associated with higher mortality and lower graft survival after LT. If possible, the cardiac defects should be addressed prior to LT.

Etiology, risk factors and management of hypertension post liver transplantation.

Cardiovascular events are one of the most important causes of morbidity and mortality in the long-term follow-up of liver transplant recipients. Hypertension is a significant cardiovascular risk factor that occurs frequently after pediatric liver transplantation. Chronic use of immunosuppressants - mainly calcineurin inhibitors - plays a major role in the development of post-transplant hypertension and circadian disturbances such as flattening of the nocturnal blood pressure dip. This requires special attention in children given the long timeframe during which immunosuppressive therapy is necessary. Careful and structured blood pressure monitoring and adequate treatment of hypertension are essential to optimize the quality of life and life expectancy of pediatric liver transplant patients. However, evidence-based guidelines for monitoring and management of post-transplant hypertension and its complications are lacking. We conducted a comprehensive review of the current knowledge and practices concerning post-transplant hypertension. The databases Pubmed, Embase, Web of Science and Google Scholar were scanned with the following keywords: pediatric liver transplantation, immunosuppression, tacrolimus, cardiovascular effects, hypertension, heart function, kidney function, circadian rhythm, mechanism, monitoring, and management. In this review, we describe the incidence and etiology of hypertension in pediatric liver transplant recipients, the underlying mechanisms and characteristics of calcineurin inhibitor-induced hypertension, and the consequences of and risk factors for post-transplant hypertension. We hereby present an overview of the current practices in blood pressure monitoring and antihypertensive treatment as well as an algorithm for the evaluation and management of hypertension post liver transplantation. Finally, we discuss knowledge gaps and suggestions for future research.

Percutaneous creation of a biliary enteric neo-anastomosis in a pediatric liver transplant patient using a vascular re-entry device

Percutaneous creation of a biliary enteric neo-anastomosis in a pediatric liver transplant patient using a vascular re-entry device

Disseminated Intravascular Coagulation as a Risk Factor for Clinical Outcome After Liver Transplantation in Pediatric Patients With Kasai Portoenterostomy Failure

Disseminated intravascular coagulation (DIC) is a serious complication in critically ill pediatric patients. This study aimed to evaluate the association between pretransplant DIC and perioperative clinical outcomes of liver transplantation (LT) in pediatric patients with Kasai portoenterostomy (KPE) failure. We enrolled pediatric patients who received LT after KPE failure between January 2005 and April 2021. We retrospectively reviewed the electronic medical records of included patients and evaluated the presence of DIC using the International Society on Thrombosis and Hemostasis (ISTH) criteria and association with perioperative clinical outcome. The study included 106 patients. Their median age and body weight at the time of pediatric intensive care unit (PICU) admission were 28.7 months and 9.25 kg, respectively. Of these patients, 23 had undergone pretransplant DIC (22%). Patients with pretransplant DIC required significantly more blood transfusions during operation. They had significantly higher serum lactate levels, pediatric end-stage liver disease scores, pediatric risk for mortality III (PRISM III) scores, longer durations of mechanical ventilator support, and longer PICU stays (all P < .05). The presence of pretransplant DIC in pediatric patients requiring LT after KPE failure was associated with poor clinical outcomes, which required more intensive and meticulous supportive management in the perioperative period of LT. DIC would be a promising prognostic factor in these patients.

Risk factors for myocardial injury during living donor liver transplantation in pediatric patients with biliary atresia.

Cold ischemia-reperfusion of the liver is an inevitable occurrence in liver transplantation that may also cause damage to the heart. Perioperative myocardial injury during liver transplantation can increase the incidence of postoperative mortality, but there is little research on the incidence of myocardial injury in children who undergo living donor liver transplantation (LDLT). Therefore, this study mainly explores the independent risk factors for myocardial injury in children who undergo LDLT. To analyze the data of children who underwent LDLT to determine the risk factors for intraoperative myocardial injury. We retrospectively analyzed the inpatient records of pediatric patients who underwent LDLT in Tianjin First Central Hospital from January 1, 2020, to January 31, 2022. Recipient-related data and donor-related data were collected. The patients were divided into a myocardial injury group and a nonmyocardial injury group according to the value of the serum cardiac troponin I at the end of surgery for analysis. Univariate analysis and multivariate logistic regression were used to evaluate the risk factors for myocardial injury during LDLT in pediatric patients. A total of 302 patients met the inclusion criteria. The myocardial injury group had 142 individuals (47%), and the nonmyocardial injury group included 160 patients (53%). Age, height, and weight were significantly lower in the myocardial injury group (P < 0.001). The pediatric end-stage liver disease (PELD) score, total bilirubin, and international standardized ratio were significantly higher in the myocardial injury group (P < 0.001). The mean arterial pressure, lactate, hemoglobin before reperfusion, duration of the anhepatic phase, cold ischemic time, incidence of postreperfusion syndrome (PRS), and fresh frozen plasma transfusion were significantly different between the two groups (P < 0.05). The postoperative intensive care unit stay and peak total bilirubin values in the first 5 d after LDLT were significantly higher in the myocardial injury group (P < 0.05). The pediatric patients with biliary atresia in the nonmyocardial injury group who underwent LDLT had a considerably higher one-year survival rate than those in the myocardial injury group (P = 0.015). Multivariate logistic regression revealed the following independent risk factors for myocardial injury: a high PELD score [odds ratio (OR) = 1.065, 95% confidence interval (CI): 1.013-1.121; P = 0.014], a long duration of the anhepatic phase (OR = 1.021, 95%CI: 1.003-1.040; P = 0.025), and the occurrence of intraoperative PRS (OR = 1.966, 95%CI: 1.111-3.480; P = 0.020). A high PELD score, a long anhepatic phase duration, and the occurrence of intraoperative PRS were independent risk factors for myocardial injury during LDLT in pediatric patients with biliary atresia.

Development and validation of a multivariable prediction model in pediatric liver transplant patients for predicting intensive care unit length of stay.

Liver transplantation is the life-saving treatment for many end-stage pediatric liver diseases. The perioperative course, including surgical and anesthetic factors, have an important influence on the trajectory of this high-risk population. Given the complexity and variability of the immediate postoperative course, there would be utility in identifying risk factors that allow prediction of adverse outcomes and intensive care unit trajectories. The aim of this study was to develop and validate a risk prediction model of prolonged intensive care unit length of stay in the pediatric liver transplant population. This is a retrospective analysis of consecutive pediatric isolated liver transplant recipients at a single institution between April 1, 2013 and April 30, 2020. All patients under the age of 18 years receiving a liver transplant were included in the study (n = 186). The primary outcome was intensive care unit length of stay greater than 7 days. Recipient and donor characteristics were used to develop a multivariable logistic regression model. A total of 186 patients were included in the study. Using multivariable logistic regression, we found that age < 12 months (odds ratio 4.02, 95% confidence interval 1.20-13.51, p = .024), metabolic or cholestatic disease (odds ratio 2.66, 95% confidence interval 1.01-7.07, p = .049), 30-day pretransplant hospital admission (odds ratio 8.59, 95% confidence interval 2.27-32.54, p = .002), intraoperative red blood cells transfusion >40 mL/kg (odds ratio 3.32, 95% confidence interval 1.12-9.81, p = .030), posttransplant return to the operating room (odds ratio 11.45, 95% confidence interval 3.04-43.16, p = .004), and major postoperative respiratory event (odds ratio 32.14, 95% confidence interval 3.00-343.90, p < .001) were associated with prolonged intensive care unit length of stay. The model demonstrates a good discriminative ability with an area under the receiver operative curve of 0.888 (95% confidence interval, 0.824-0.951). We develop and validate a model to predict prolonged intensive care unit length of stay in pediatric liver transplant patients using risk factors from all phases of the perioperative period.

Risk factors for postreperfusion syndrome during living donor liver transplantation in paediatric patients with biliary atresia: a retrospective analysis

BackgroundLiving donor liver transplantation (LT) is the main treatment for paediatric biliary atresia (BA) in Asia. During LT, a series of haemodynamic changes often occur during LT reperfusion, which is...

Portal Dynamics After Living Donor Liver Transplant in Pediatric Recipients: A 10-Year Follow-Up Retrospective Study

It may be difficult for pediatric patients to evaluate the impact of liver transplantation (LT) on splenomegaly due to the natural growth course. The long-term dynamics of portal vein (PV) size and PV flow after LT in pediatric patients are unclear. We aimed to evaluate the long-term transition of the splenic size, PV size, and PV flow velocity in pediatric patients who underwent successful living donor liver transplantation (LDLT) and survived >10 years. From October 2004 to December 2010, 39 pediatric patients (25 boys; 14 girls) underwent LDLT, received pre-LDLT and post-LDLT computed tomography scans and long-term ultrasound sonography follow-up, and survived >10 years without additional intervention at our institution. We analyzed the short- to mid-term and long-term impact of LDLT on splenic size, PV size, and PV flow velocity over time. The PV diameter increased throughout the 10-year follow-up (P < .001). The PV flow velocity increased 1 day after LDLT (P< .001); proceeded to decrease 3 days after LDLT, reaching a low point 6 to 9 months after LDLT; and remained stable throughout the 10-year follow-up. Regression of the splenic volume at 6 to 9 months after LDLT (P < .001) was noted. However, the splenic size steadily increased on long-term follow-up. Although LDLT has a significant short-term reduction effect on splenomegaly, the long-term transitional trend of the splenic size and PV diameter may increase along with children's growth. The PV flow reached a stable status 6 to 9 months after LDLT and remained so until 10 years after LDLT.

The Ratio of Intraoperative Red Blood Cell Transfusion to Blood Loss Associated with Early Postoperative Complications in Pediatric Liver Transplantation Patients

Introduction: Liver transplantation (LT) is an operation purposed to save the lives of children with acute or chronic liver diseases, hepatic tumors, and some genetic and metabolic diseases. However, patients who underwent LT have a significant risk of intraoperative blood loss and red blood cell (RBC) transfusion, especially in pediatric patients. Methods: In this study, 569 pediatric patients (<18 years old) who underwent LT at a tertiary university hospital between 2013 and 2020 were included. Multiple logistic regression was used to analyze the association between the ratio of intraoperative RBC transfusion to blood loss (IRTBL) and the complications after LT in pediatric patients. IRTBL was divided into quartiles in the adjusted model. Odds ratios, 95% confidence intervals, and p values for trends were calculated. Restricted cubic spline (RCS) regression was used to evaluate the nonlinear association between IRTBL and complications. Results: Compared with the lowest level and the highest level of IRTBL, Q2 and Q3 quartiles of IRTBL showed significantly positive association with early complications. A significantly nonlinear association was observed between the IRTBL and early complications in the RCS model with the multiple adjustments of potential covariates (P overall<0.01, P nonlinear<0.01). However, no significant association was observed between late complications and IRTBL. Conclusion: In this study, we found there was a nonlinear relationship between the ratio of IRTBL and early postoperative complications in pediatric LT patients, which provides a theoretical basis for RBC transfusion in pediatric LT patients.

Outcomes in pediatric liver transplant recipients receiving bilateral continuous erector spinae plane blocks.

Regional anesthesia allows for opioid-sparing and enhanced recovery after many major surgeries. Erector spinae blockade, with reduced bleeding risk and the option for continuous infusion, offers an opportunity to promote this principle in pediatric liver transplant patients. Our goal was to evaluate pain scores, opioid use, and return of bowel function following continuous ESP blockade in pediatric liver transplant recipients. This retrospective cohort study included extubated patients who received a liver transplant at St. Louis Children's Hospital from July 2016 to July 2021. The control group, which did not meet the criteria for ESP blockade and received standard analgesia regimens, was compared to the group receiving continuous ESP blockade. Measured outcomes included pain scores, opioid consumption through postoperative day two, date of first bowel movement, and length of stay in the ICU and the hospital. Patient demographics between control and ESP groups showed no significant differences. Pain scores between control and ESP groups also showed no significant differences. Intraoperative and postoperative opioid requirements, studied in oral morphine equivalents per kilogram (OME/kg), were significantly lower for patients with ESP blockade. Time to first bowel movement was also significantly earlier for the ESP group. No significant differences were found in length of ICU or hospital stay. There were no safety concerns or complications related to ESP blockade. Use of continuous ESP blockade resulted in reduced opioid consumption through postoperative day two and earlier return of bowel function.

2150. Surgical Prophylaxis in Pediatric Liver Transplant Recipients: Variations in Protocol and Impact on 30-Day Surgical Site Infections

Abstract Background Children undergoing liver transplantation are at risk for surgical site infections (SSI). IDSA/ASHP/SIS/SHEA guidelines recommend surgical prophylaxis with a third-generation cephalosporin plus ampicillin or piperacillin-tazobactam alone. The study objectives were to describe the surgical prophylaxis used at our institution, obtain data on whether prophylactic antimicrobials are adjusted for multidrug resistant organisms and to determine whether adjustments correlate with SSI. Methods Pediatric liver transplant procedures, with associated peri-operative and intra-operative antimicrobials, were extracted from our institutions’ Anesthesia Record Keeping System (ARKS) between 2005-2022. Medical records were reviewed for demographics, microbiological data (e.g., colonization), protocol deviations and 30-day CDC/NHSN SSIs. Results Seventy-one procedures were performed in 69 patients, median age 3 years (range, 5 months- 17 years), where 89% had a pre-transplant infectious disease consultation. Variations from protocol occurred in 39% (n=28), of which 3 were consult-directed. Sixteen were colonized with an organism prior to transplant (3 MDRO and 1 Candida spp.), of which 10 had a protocol adjustment (p&amp;lt; 0.001). The most common additional antimicrobials were vancomycin (n=17) and fluconazole (n=8). Reasons for fluconazole were fulminant liver failure (n=2), surgeon concern (n=3), colonization or prolonged antimicrobials prior to transplant (n=2) and continuation of prophylaxis (n=1). Ten procedures were complicated by an SSI (14%). SSI rates did not differ in those with and without protocol adjustments (p=0.50). Conclusion Adjustments to guideline concordant surgical prophylaxis recommendations occurred in 39% of pediatric liver transplant procedures, with the most common being addition of vancomycin or fluconazole. Adjustments were based on a pre-transplant infectious disease consult recommendations in 11% of cases. Protocol adjustment correlated with any pretransplant microbiology culture result, but not with either MDRO colonization or subsequent SSI. Antimicrobial stewardship efforts may be indicated to address variations in antimicrobial prophylaxis in pediatric liver transplant patients. Disclosures All Authors: No reported disclosures.

Intestinal Dominance by Multidrug-Resistant Bacteria in Pediatric Liver Transplant Patients.

Pediatric liver transplantation (PLTx) is commonly associated with extensive antibiotic treatments that can produce gut microbiome alterations and open the way to dominance by multidrug-resistant organisms (MDROs). In this study, the relationship between intestinal Relative Loads (RLs) of β-lactamase genes, antibiotic consumption, microbiome disruption, and the extraintestinal dissemination of MDROs among PLTx patients is investigated. 28 PLTx patients were included, from whom 169 rectal swabs were collected. Total DNA was extracted and blaCTX-M-1-Family, blaOXA-1, blaOXA-48, and blaVIM were quantified via quantitative polymerase chain reaction (qPCR) and normalized to the total bacterial load (16SrRNA) through LogΔΔCt to determine the RLs. 16SrRNA sequencing was performed for 18 samples, and metagenomic sequencing was performed for 2. Patients' clinical data were retrieved from the hospital's database. At least one of the genes tested were detected in all of the patients. The RLs for blaCTX-M-1-Family, blaOXA-1, blaOXA-48, and blaVIM were higher than 1% of the total bacterial population in 67 (80.73%), 56 (78.87%), 57 (77.03%) and 39 (61.9%) samples, respectively. High RLs for blaCTX-M-1-Family, blaOXA-1, and/or blaOXA-48, were positively associated with the consumption of carbapenems with trimethoprim-sulfamethoxazole and coincided with low diversity in the gut microbiome. Low RLs were associated with the consumption of noncarbapenem β-lactams with aminoglycosides (P < 0.05). Extraintestinal isolates harboring the same gene(s) as those detected intraintestinally were found in 18 samples, and the RLs of the respective swabs were high. We demonstrated a relationship between the consumption of carbapenems with trimethoprim-sulfamethoxazole, intestinal dominance by MDROs and extraintestinal spread of these organisms among PLTx patients. IMPORTANCE In this study, we track the relative intestinal loads of antibiotic resistance genes among pediatric liver transplant patients and determine the relationship between this load, antibiotic consumption, and infections caused by antibiotic-resistant organisms. We demonstrate that the consumption of broad spectrum antibiotics increase this load and decrease the gut microbial diversity among these patients. Moreover, the high loads of resistance genes were related to the extraintestinal spread of multidrug-resistant organisms. Together, our data show that the tracking of the relative intestinal loads of antibiotic resistance genes can be used as a biomarker that has the potential to stop the extraintestinal spread of antibiotic-resistant bacteria via the measurement of the intestinal dominance of these organisms, thereby allowing for the application of preventive measures.

Population pharmacokinetics of sublingually administered tacrolimus in infants and young children with liver transplantation.

Pharmacokinetics of tacrolimus after sublingual administration is not characterized in paediatric liver transplant patients. Therefore, we aimed to develop a population pharmacokinetic model of sublingually administered tacrolimus in patients who cannot swallow the capsules due to their age, sedation status and/or mechanical ventilation during the first weeks post-transplantation. Demographic, clinical and pharmacological variables, including tacrolimus whole blood concentrations obtained from therapeutic drug monitoring and data from dense-sampling pharmacokinetic profiles, were recorded in 26 paediatric patients with biliary atresia who underwent liver transplantation between 2016 and 2021. Population pharmacokinetic analysis was performed with NONMEM v7.4. Disposition of tacrolimus was best characterized by a 2-compartment model with clearance achieving half of the maximum elimination capacity (CLMAX =4.1L/h) at 4.6days post-transplantation (T50 ). Compared to sedated patients, nonsedated status showed an increased first-order absorption rate constant (1.1 vs. 0.1h-1 ) and a 24% reduction in bioavailability (FNS ) at 14 days post-transplant. The model was able to explain the oral absorption pattern in nonsedated patients as the result of gut bioavailability (0.9) and hepatic extraction ratio, with the latter being responsible for first-pass effects. Estimates of interindividual variability remained moderate (25.9% for the gut bioavailability) to high (79.8% for the apparent volume of distribution of the central compartment, and 101% for T50 ). A population pharmacokinetic model of sublingually administered tacrolimus in paediatric patients was developed to characterize different absorption mechanisms. Once the model is externally validated, the effect of post-transplant time on clearance and the sedation status may be considered in routine dosing management.

Scoliosis After Liver Transplantation in Pediatric Patients

Objective: Little is known about the development of scoliosis after pediatric liver transplantation. In this study, we aimed to evaluate the frequency of scoliosis and its relationship with potential risk factors in children after liver transplantation. Methods: Pediatric liver transplantations (under of age 18) performed between January 2009 and December 2017 at Malatya İnönü University Institute of Liver Transplantation were scanned retrospectively. In the spinal axis, &gt;10° lateral deviations were accepted as scoliosis. The curve patterns were classified according to the Lenke classification. Results: Among 287 pediatric liver transplantationss, 17 of them were scoliosis (6%). Nine patients were females and eight were males. The median Cobb angle was 12° at the time of diagnosis and then 17° at the last follow-up. According to the Lenke classification, 11 patients had type 5 curve pattern. During the follow-up period (ranging from 1 to 11 years), scoliosis progression was slow and no patient requiring surgical treatment was detected. Conclusion: We found that the prevalence of scoliosis increased after pediatric liver transplantation, but we do not have any definite information about the cause. Comparable new studies with more patients are needed to make a definitive conclusion in this regard.