• diagnostic testing
• infection
• solid organ transplant

• Karius, Inc

• P01 AI152999 NIAID NIH HHS
• National Institute of Allergy and Infectious Diseases
• National Institutes of Health
• Houston Methodist

• aspergillosis
• critical care
• immunosuppression
• intensive care unit
• solid organ transplantation

Immunosuppression is an important factor in the incidence of infections in transplant recipient. Few studies are available on the management of immunosuppression (IS) treatment in the liver transplant (LT) recipients complicated with infection. The aim of this study is to describe our experience in the management of IS treatment during bacterial bloodstream infection (BSI) in LT recipients and assess the effect of temporary IS withdrawal on 30 d mortality of recipients presenting with severe infection.

To assess the effect of temporary IS withdrawal on 30 d mortality of LT recipients presenting with severe infection.

A retrospective study was conducted with patients diagnosed with BSI after LT in the Department of Liver Surgery, Renji Hospital from January 1, 2016 through December 31, 2017. All recipients diagnosed with BSI after LT were included. Univariate and multivariate Cox regression analysis of risk factors for 30 d mortality was conducted in the LT recipients with Gram-negative bacterial (GNB) infection.

Seventy-four episodes of BSI were identified in 70 LT recipients, including 45 episodes of Gram-positive bacterial (GPB) infections in 42 patients and 29 episodes of GNB infections in 28 patients. Overall, IS reduction (at least 50% dose reduction or cessation of one or more immunosuppressive agent) was made in 28 (41.2%) cases, specifically, in 5 (11.9%) cases with GPB infections and 23 (82.1%) cases with GNB infections. The 180 d all-cause mortality rate was 18.5% (13/70). The mortality rate in GNB group (39.3%, 11/28) was significantly higher than that in GPB group (4.8%, 2/42) (P = 0.001). All the deaths in GNB group were attributed to worsening infection secondary to IS withdrawal, but the deaths in GPB group were all due to graft-versus-host disease. GNB group was associated with significantly higher incidence of intra-abdominal infection, IS reduction, and complete IS withdrawal than GPB group (P < 0.05). Cox regression showed that rejection (adjusted hazard ratio 7.021, P = 0.001) and complete IS withdrawal (adjusted hazard ratio 12.65, P = 0.019) were independent risk factors for 30 d mortality in patients with GNB infections after LT.

IS reduction is more frequently associated with GNB infection than GPB infection in LT recipients. Complete IS withdrawal should be cautious due to increased risk of mortality in LT recipients complicated with BSI.

• Immunosuppressive therapy
• Liver transplantation
• Bloodstream infection
• Multidrug-resistant gram-negative bacterium

• Bacteremia/epidemiology
• Gram-Negative Bacterial Infections/epidemiology
• Humans
• Immunosuppression Therapy/adverse effects
• Liver Transplantation/adverse effects
• Retrospective Studies
• Risk Factors
• Sepsis
• Transplant Recipients

• liver
• liver transplantation
• living donor liver transplantation
• post-transplant infection

• Adolescent
• Adult
• Aged
• Bacterial Infections/immunology
• End Stage Liver Disease/immunology
• End Stage Liver Disease/surgery
• Female
• Humans
• Immunosuppression Therapy/adverse effects
• Liver Transplantation/adverse effects
• Liver Transplantation/methods
• Living Donors
• Male
• Middle Aged
• Mycoses/immunology
• Postoperative Complications/immunology
• Postoperative Complications/microbiology
• Postoperative Complications/mortality
• Retrospective Studies
• Risk Factors
• Severity of Illness Index
• Young Adult

Bloodstream infection (BSI) is a common complication after living-donor liver transplantation (LDLT). Some patients develop recurrent BSIs. We evaluated the impacts of early recurrent BSIs (ER-BSIs) on outcomes in LDLT recipients. LDLT cases between 2008 and 2016 were included. Early BSI (E-BSI) was defined as a BSI event that occurred within 2 months after LDLT. ER-BSIs were defined as new-onset BSIs within 2 months due to another pathogen at a ≥ 48-h interval or a relapse of BSIs by the same pathogen at a ≥ 1-week interval, with negative cultures in between. The primary objective was evaluating the all-cause mortality of each group of LDLT recipients (90 days and 1 year). The secondary objectives were analyzing associated factors of each all-cause mortality and risk factors for early single BSI and ER-BSI. Among 727 LDLT recipients, 108 patients experienced 149 events of E-BSI with 170 isolated pathogens. Twenty-eight patients (25.9%, 28/108) experienced ER-BSI. The 1-year survival rates of patients without BSI, with early single BSI event, and with ER-BSIs were 92.4%, 81.3%, and 28.6%, respectively. ER-BSI was the most significant risk factor for 1-year mortality (adjusted HR = 5.31; 95% CI = 2.27–12.40). Intra-abdominal and/or biliary complications and early allograft dysfunction were risk factors for both early single BSI and ER-BSI. Interestingly, longer cold ischemic time and recipient operative time were associated with ER-BSI. LDLT recipients with ER-BSI showed very low survival rates accompanied by intra-abdominal complications. Clinicians should prevent BSI recurrence by being aware of intra-abdominal complications.

• Bacteremia
• Fungemia
• Living-donor liver transplantation
• Mortality
• Recurrence

• blood stream infection
• end stage liver disease
• liver transplant
• low and middle income country
• mortality
• pediatric

• Bacteraemia
• Enterococci
• Liver transplantation
• Mortality
• Vancomycin resistance

• Aged
• Bacteremia/microbiology
• Bacteremia/mortality
• Drug Resistance, Multiple, Bacterial
• Female
• Fungi/isolation & purification
• Gram-Negative Bacteria/isolation & purification
• Gram-Positive Bacteria/isolation & purification
• Humans
• Incidence
• Liver Cirrhosis/etiology
• Liver Cirrhosis/microbiology
• Liver Cirrhosis/surgery
• Liver Transplantation/adverse effects
• Male
• Middle Aged
• Postoperative Complications/microbiology
• Postoperative Complications/mortality
• Retrospective Studies

Pseudomonas aeruginosa bacteremia remains as a life-threatening complication after liver transplantation (LT) and is intractable because of the high rate of drug resistance to commonly used antibiotics. To better understand the characteristics of this postoperative complication, PubMed and Embase searches as well as reference mining was done for relevant literature from the start of the databases through August 2018. Among LT recipients, the incidence of P. aeruginosa bacteremia ranged from 0.5% to 14.4% and mortality rates were up to 40%. Approximately 35% of all episodes of bloodstream infections (BSIs) were P. aeruginosa bacteremia, of which 47% were multidrug resistant and 63% were extensively drug resistant. Several factors are known to affect the mortality of LT recipients with P. aeruginosa bacteremia, including hypotension, mechanical ventilation, and increasing severity of illness. In LT recipients with P. aeruginosa bacteremia, alteration in DNA gyrase A genes and overexpression of proteins involved in efflux systems, namely the expression of KPC-2-type carbapenemase, NDM-1, and VIM-2-type MBL, contribute to the high resistance of P. aeruginosa to a wide variety of antibiotics. Because of complicated mechanisms of drug resistance, P. aeruginosa causes high morbidity and mortality in bacteremic LT patients. Consequently, early detection and treatment with adequate early targeted coverage for P. aeruginosa BSI are of paramount importance in the early posttransplantation period to obtain a better prognosis for LT patients.

• antimicrobial resistance
• liver transplantation
• morbidity and mortality
• risk factor
• solid organ transplantation

Multiple drug resistant/extensively drug resistant (MDR/XDR) Gram-negative urinary tract infections (UTIs) represent a growing threat to kidney transplant recipients. This retrospective study aimed to assess the incidence and microbiological profile of MDR/XDR Gram-negative UTIs, to identify drug susceptibility of MDR/XDR bacteria, and to determine the potential risk factors for MDR/XDR UTIs in kidney recipients.

During the study period, 1569 patients underwent consecutive kidney transplantation in two transplantation centers. We studied the demographics, clinical characteristics, and urine culture data from kidney recipients with MDR/XDR Gram-negative UTIs, and verified the risk factors associated with MDR/XDR infections.

Eighty-one kidney recipients yielded 88 episodes of MDR/XDR Gram-negative UTIs with five patients (6.2%) succumbing to all-cause in-hospital mortality. The most frequently isolated bacterium was Escherichia coli (62.5%). Almost all MDR/XDR Gram-negative bacteria were resistant to first- and second-generation cephalosporin, and monocyclic beta-lactam. They were relatively sensitive to meropenem, amikacin, and tigecycline. As for the 12 XDR bacteria, all of them were resistant to meropenem and 25% of them were resistant to tigecycline. All XDR Acinetobacter baumannii and E. coli were susceptible to tigecycline. Nosocomial infection (odds ratio [OR] = 11.429, 95% CI = 1.311–99.625, P = 0.027) was the only independent predictor of MDR/XDR Gram-negative UTIs. Non-fermenting bacterial infection (OR = 20.161, 95% CI = 3.409–119.240, P = 0.001), polycystic kidney disease (OR = 39.871, 95% CI = 1.979–803.384, P = 0.016), and serum creatinine level > 1.5 mg/dL (OR = 8.688, 95% CI = 1.354–55.747, P = 0.023) were significantly different between XDR and MDR Gram-negative UTIs.

Meropenem, amikacin, and/or tigecycline can be prescribed for MDR/XDR Gram-negative infections. Tigecycline can also be prescribed for XDR A. baumannii and E. coli. Nosocomial infection was a risk factor for MDR/XDR Gram-negative UTIs, while XDR UTIs were associated with non-fermenting bacterial infection, polycystic kidney disease, and impaired renal function.

• MDR
• XDR
• bacteria
• kidney transplantation
• risk factors
• urinary tract infections

• bacteremia
• liver transplantation
• methicillin-resistant Staphylococcus aureus
• morbidity
• mortality
• risk factors

• drug resistance
• infection
• liver
• microbial perioperative care
• risk factors
• transplantation

• Cross infection
• Enfermería
• Infección
• Infección nosocomial
• Infection
• Liver transplant
• Nursing
• Trasplante hepático

• Enterococcus
• Pseudomonas aeruginosa
• acidic sophorolipids
• adjuvants
• antimicrobial activity
• endothelium
• growth inhibition
• in vivo
• keratinocytes
• microbial pathogens
• wound healing

Although multidrug-resistant (MDR) gram-negative bacteremia (GNB) has been recognized as an important cause of morbidity and mortality among abdominal solid organ transplant (ASOT) recipients, there are no data on its prognostic factors after an interim standard definition of MDR was proposed in 2012. The objective of this study was to describe the epidemiology, microbiology, and predictors of infection-related 30-day mortality in ASOT recipients with MDR GNB.

We performed a retrospective, double-center analysis of ASOT patients with MDR GNB over a 13-year study period. Univariate and multivariate analyses were performed to identify the risk factors for mortality.

During the observational period, 2169 subjects underwent ASOT. Ninety-nine episodes of MDR GNB were diagnosed in 91 (4.6%) ASOT recipients, with a predominance of E.coli (29 isolates, 29.3%) and A.baumanii (24 isolates, 24.2%). The median age of these 91 recipients was 45 years (interquartile range 35–54). Mortality after the first episode of MDR GNB was 39.6% (36 deaths). The univariate analysis identified the following variables as predictors of MDR GNB-related mortality: lung focus (P = 0.001),nosocomial origin (P = 0.002), graft from donation after cardiac death or deceased donors (P = 0.023), presence of other concomitant bloodstream infection (P < 0.001), temperature of 40 °C or greater at the onset of MDR GNB (P = 0.039), creatinine > 1.5 mg/dl (P = 0.006), albumin < 30 g/L (P = 0.009), platelet count < 50,000/mm³ (P < 0.001), and septic shock (P < 0.001). In the multivariate logistic regression analysis, septic shock (odds ratio (OR) = 160.463, 95% confidence interval (CI) = 19.377–1328.832, P < .001), as well as creatinine > 1.5 mg/dl (OR = 24.498, 95% CI = 3.449–173.998, P = 0.001), nosocomial origin (OR = 23.963, 95% CI = 1.285–46.991, P = 0.033), and presence of other concomitant bloodstream infections (OR = 27.074, 95% CI = 3.937–186.210, P = 0.001) were the variables associated with MDR GNB-related 30-day mortality.

MDR GNB was associated with high morbidity and mortality in ASOT recipients, with a predominant causative organisms being E.coli and A.baumanii. Nosocomial origin, as well as presence of other concomitant bloodstream infections, increased creatinine level and septic shock were the main predictors of MDR GNB-related 30-day mortality.

• Abdominal solid organ transplantation
• Gram-negative bacteremia
• Mortality
• Multidrug-resistant
• Predictors

• Cellular immunity
• ImmuKnow® assay
• Immunological monitoring
• Liver transplant recipients
• Pathogens

Pseudomonas aeruginosa infection remains a life-threatening complication after solid organ transplantation (SOT). We aimed to investigate the distribution and drug susceptibility of pathogens, and clinical characteristics of SOT recipients with Pseudomonas aeruginosa infections.

A total of 55 SOT recipients who developed 61 episodes of Pseudomonas aeruginosa infections between January 1, 2003 and July 31, 2015 were retrospectively analyzed. The distribution and the drug susceptibility of Pseudomonas aeruginosa were reviewed.

The most common site from which 61 Pseudomonas aeruginosa rods were isolated were the lungs (57.4%, n=37), followed by the blood (27.9%, n=17). There were 35, 18, and 9 recipients accompanied with a serum creatinine level of >1.5 mg/dL, lymphocyte count of <300/mm³, and a serum albumin level of <30 g/L, respectively. Seven patients each presented with white blood cell count of >15 000/mm³ and platelet count of <50 000/mm³. There were 6 (10.9%) cases of septic shocks and 18 (32.7%) deaths. Antibiotic resistance rate of all Pseudomonas aeruginosa to 4 of 10 antibiotics investigated was more than 50%. Of these 61 Pseudomonas aeruginosa isolates, 47.5% were carbapenem-resistant. The rods were relatively sensitive to piperacillin-tazobactam, levofloxacin, amikacin, and cefoperazone-sulbactam (resistance rate <40%).

The clinical presentation of Pseudomonas aeruginosa infections included high body temperature, decreased platelet count, elevated white blood cell count, a high nosocomial origin and mortality, and onset in the late period after transplantation. According to our findings, piperacillin-tazobactam, levofloxacin, amikacin, and cefoperazone-sulbactam, alone or combination, are recommended to treat SOT recipients with Pseudomonas aeruginosa infections.

• Acinetobacter baumannii
• drug resistance
• infections
• liver transplantation
• manifestation

Drug-resistant Acinetobacter baumannii has become a major problem in liver transplant recipients. The aim of this study was to investigate the clinical presentation, distribution, and drug susceptibility characteristics in liver recipients with A. baumannii infection.

We retrospectively investigated 17 liver recipients who developed A. baumannii infection between January 1, 2007 and December 31, 2014. The distribution of A. baumannii and drug susceptibility characteristics were reviewed.

Infectious complications due to A. baumannii appeared in 17 liver recipients, with a total of 24 episodes. Approximately 63% (15/24) of A. baumannii infections occurred within 2 weeks after transplantation. The most common source of infection was multiple culture-positive sites (35.3%, n=6), followed by the intra-abdominal/biliary tract (23.5%, n=4) and lung (23.5%, n=4). Eight patients (47.1%) had a body temperature of 38°C or higher at the onset of A. baumannii infection. Nine, seven, and 12 recipients had a serum creatinine level of >1.5 mg/dL, a white blood cell count of >15,000/mm³, and a platelet count of <50,000/mm³, respectively. There were five (29.4%) cases of septic shock and eight (47.1%) deaths. The rate of antibiotic resistance of A. baumannii to ten of 12 antibiotics investigated was more than 60%. Among the 24 infections caused by A. baumannii, 75% were carbapenem-resistant. The rods were relatively sensitive to tigecycline and cefoperazone-sulbactam.

The clinical manifestations of A. baumannii infection included a high body temperature, a decreased platelet count, an elevated white blood cell count, and onset in the early period after transplantation as well as high mortality. The antibiotic resistance rate of A. baumannii was extremely high. Prevention measures and combination antibiotic therapy are needed to improve the outcomes of liver recipients with A. baumannii infections.

• Acinetobacter baumannii
• drug resistance
• infections
• liver transplantation
• manifestation

• Bacterial Infections/epidemiology
• Female
• Humans
• Liver Transplantation
• Male
• Mycoses/epidemiology
• Polymerase Chain Reaction
• Population Surveillance
• Postoperative Period

Infectious complications are major causes of morbidity and mortality after liver transplantation, despite recent advances in the transplant field. Bacteria, fungi, viruses and parasites can cause infection before and after transplantation. Among them, bacterial infections are predominant during the first two months post-transplantation and affect patient and graft survival. They might cause surgical site infections, including deep intra-abdominal infections, bacteremia, pneumonia, catheter-related infections and urinary tract infections. The risk factors for bacterial infections differ between the periods after transplant, and between centers. Recently, the emergence of multi-drug resistant bacteria is great concern in liver transplant (LT) patients. The instructive data about effects of infections with extended-spectrum beta lactamase producing bacteria, carbapenem-resistant gram-negative bacteria, and glycopeptide-resistant gram-positive bacteria were reported on a center-by-center basis. To prevent post-transplant bacterial infections, proper strategies need to be established based upon center-specific data and evidence from well-controlled studies. This article reviewed the recent epidemiological data, risk factors for each type of infections and important clinical issues in bacterial infection after LT.

• Liver transplantation
• Bacterial infection
• Intraabdominal infections
• Resistant bacteria

• Anti-Bacterial Agents/therapeutic use
• Bacteremia/complications
• Bacterial Infections/complications
• Colitis/complications
• Colitis/microbiology
• Communicable Disease Control
• Drug Resistance, Multiple, Bacterial/drug effects
• Humans
• Immunosuppressive Agents/adverse effects
• Incidence
• Liver Diseases/complications
• Liver Diseases/surgery
• Liver Transplantation/adverse effects
• Pneumonia/complications
• Pneumonia/microbiology
• Risk Factors
• Urinary Tract Infections/complications
• Urinary Tract Infections/microbiology

Infections after liver transplantation are the main cause of death in the first year. Recent reports indicate that NOD2 gene mutations increase the risk for inflammatory bowl disease and the severity of graft-versus-host disease in bone marrow transplant patients. Data on polymorphisms in liver transplant patients are sparse. We analyzed 13 single-nucleotide polymorphisms (SNPs) of 13 different gene variants including the SNPs of NOD2 genes from liver recipients. The aim of the study was to evaluate the impact of the SNPs on dialysis-dependent kidney failure, the incidence of infections and patient survival.

During a period of 20-months, 231 patients were recruited in this non-interventional, prospective study. Thirteen different SNPs and their impact on the patients’ survival, infection rate, and use of dialysis were assessed.

NOD 2 wildtype genes were protective with respect to the survival of non-alcoholic, cirrhotic transplant patients (3 year survival: 66.8% wildtype vs. 42.6% gene mutation, p = 0.026). This effect was not observed in alcoholic transplant recipients.

The incidence of dialysis-dependent kidney failure and infection in the liver transplant patients was not influenced by NOD 2 gene polymorphisms. No effect was noted in the remaining 12 SNPs.

Patients with early allograft dysfunction experienced significantly more infections, required dialysis and had significantly worse survival.

In contrast, the donor-risk-index had no impact on the infection rate, use of dialysis or survival.

NOD2 gene variants seem to play a key role in non-alcoholic, liver transplant recipients. However these data should be validated in a larger cohort.

• Bacteremia/drug therapy
• Bacteremia/microbiology
• Biofilms
• Catheter-Related Infections/drug therapy
• Catheter-Related Infections/microbiology
• Cross Infection/drug therapy
• Cross Infection/microbiology
• Drug Resistance, Bacterial
• Humans
• Prosthesis-Related Infections/drug therapy
• Prosthesis-Related Infections/microbiology
• Staphylococcal Infections/drug therapy
• Staphylococcal Infections/microbiology
• Staphylococcus epidermidis/drug effects
• Staphylococcus epidermidis/physiology
• Surgical Wound Infection/drug therapy
• Surgical Wound Infection/microbiology

Liver transplantation is the only therapeutic modality for patients with acute-on chronic liver failure (ACLF). These patients are at high risk for bacterial infections while awaiting transplantation. The aim of this study was to elucidate whether an adequately treated bacterial infection influences the outcomes after transplantation in this patient population.

54 recipients (median age, 49.5 years [range, 22–60]) of adult-to-adult living donor liver transplant (LDLT) for ACLF were categorized as those with pretransplant infection (Group 1, n = 34) or without pretransplant infection (Group 2, n = 20) for retrospective analyses. With the exception of a higher male-female ratio (P = 0.046) and longer length of pretransplant hospital stay (P = 0.026) in Group 1, similar demographic, laboratory and clinical features were found in both groups. Patients in Group 1 (totally 42 pretransplant infection episodes) were adequately treated with effective antibiotic(s) before receiving LDLT. All included patients were followed up until one year after transplantation or death. Sixty-one posttransplant infection episodes were found in an overall of 44 ACLF patients (27 in Group 1 vs. 15 in Group 2; P = 0.352). Frequently encountered posttransplant infections were intraabdominal infection, pneumonia, bloodstream infection and urinary tract infection. Two patients died in each group (P = 0.622). No significant difference was found in the length of posttransplant ICU stay, and in one-year survival, graft rejection, and posttransplant infection rate between both groups. The longer overall hospital stay (mean day, 89.0 vs. 65.5, P = 0.024) found in Group 1 resulted from a longer pretransplant hospital stay receiving treatment for pretransplant infection(s) and/or awaiting transplantation.

These data suggested that an adequately treated pretransplant infection do not pose a significant risk for clinical outcomes including posttransplant fatality in recipients in adult-to-adult LDLT for ACLF.

• Adult
• Bacterial Infections/complications
• Female
• Graft Rejection
• Graft Survival
• Humans
• Liver Failure/microbiology
• Liver Failure/surgery
• Liver Transplantation
• Male
• Middle Aged
• Retrospective Studies
• Young Adult

Since the introduction of the Milan criteria in 1996, liver transplantation has become a standard therapy for end-stage liver diseases and hepatocellular carcinoma. In recent years, liver transplantation has developed greatly. Survival rates after liver transplantation have markedly improved as a result of improved operative techniques, use of immunosuppressants, etc. But infection, especially enterogenic infection, is still the most disturbing complication in patients undergoing liver transplantation. This article gives an overview of infection after liver transplantation and focuses on the discussion of enterogenic infection in terms of its pathophysiology, risk factors, outcome, diagnosis and treatment.

• Liver transplantation
• Infection
• Enterogenic infection