Episodes Of Bacterial Infection Research Articles

Hepatolithiasis: Epidemiology, presentation, classification and management of a complex disease.

The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts, above the hilar confluence of the hepatic ducts. The disease is more prevalent in Asia, mainly owing to socioeconomic and dietary factors, as well as the prevalence of biliary parasites. In the last century, owing to migration, its global incidence has increased. The main pathophysiological mechanisms involve cholangitis, bile infection and biliary strictures, creating a self-sustaining cycle that perpetuates the disease, frequently characterised by recurrent episodes of bacterial infection referred to as syndrome of "recurrent pyogenic cholangitis". Furthermore, long-standing hepatolithiasis is a known risk factor for development of intrahepatic cholangiocarcinoma. Various classifications have aimed at providing useful insight of clinically relevant aspects and guidance for treatment. The management of symptomatic patients and those with complications can be complex, and relies upon a multidisciplinary team of hepatologists, endoscopists, interventional radiologists and hepatobiliary surgeons, with the main goal being to offer relief from the clinical presentations and prevent the development of more serious complications. This comprehensive review provides insight on various aspects of hepatolithiasis, with a focus on epidemiology, new evidence on pathophysiology, most important clinical aspects, different classification systems and contemporary management.

Epidemiology and Risk Factors of Early Bacterial Infections After Pediatric Living Donor Liver Transplantation

Advancements in surgical techniques, immunosuppression regimens, and peri-operative and postoperative care have resulted in marked improvement in outcomes after pediatric living donor liver transplantation (PLDLT). Despite these developments, infectious complications remain a major cause of morbidity and mortality. This is a retrospective cohort analysis of pediatric recipients from January 2004 to December 2018. Patients were classified into infected and non-infected groups based on the occurrence of bacterial infection during the first 3 months after transplant. Perioperative risk factors for early post-transplant bacterial infections and postoperative outcomes were investigated. Seventy-two out of 221 children developed early bacterial infection (32.6%). The first episodes of bacterial infection most frequently occurred in the second week after LDLT (37.5%). In multivariate analysis, active infection before transplant and complications with Clavien-Dindo grading >3 were the only independent risk factors. Early bacterial infections were independently associated with longer intensive care unit stays, longer hospital stays, and a higher incidence of readmission for bacterial infection during the first year after transplant. Additionally, the overall patient survival rate was significantly higher in the non-infected group (P = .001). Risk factors for infection, such as age, weight, disease severity, ABO-incompatible, and other operative factors, were not identified as independent risk factors. We have demonstrated that there are similarities and disparities in the epidemiology and risk factors for early bacterial infection after transplant between centers. Identification and better characterization of these predisposing factors are essential in the modification of current preventive strategies and treatment protocols to improve outcomes for this highly vulnerable group.

Bacterial infections as a risk factor for non-neoplastic portal vein thrombosis development in cirrhotic patients.

Portal vein thrombosis (PVT) and sepsis are common complications in patients with liver cirrhosis. Factors that lead to PVT are not completely understood. This study aimed to investigate the possible association between bacterial infections and the development of PVT in cirrhotic patients. 202 consecutive cirrhotic patients without previous infections, followed at the Liver Unit in Verona Hospital, were enrolled from 2017 to 2021 (median follow-up 3.3 years). During the follow-up period, PVT was diagnosed by ultrasound, CT and/or MRI, and episodes of bacterial infections requiring hospitalization were recorded. Malignant PVT was an exclusion criterion. Of the 202 patients enrolled (68.3% males, mean age 63.8±11 years), 22 (10.8%) developed PVT during the follow up. In patients with PVT, the prevalence of previous bacterial infections was significantly higher compared to patients without PVT (63.6% vs 31.1%; p=0.02). Cox regression analysis revealed that a history of bacterial infection was the only variable that demonstrated a significant association with the risk of de novo PVT occurrence (HR 4.04, 95% CI: 1.68-9.65). in patients with liver cirrhosis bacterial infections are a predisposing factor for the following development of PVT. Further studies are needed to confirm this evidence.

Incidence and risk factors of neonatal bacterial infections: a community-based cohort from Madagascar (2018–2021)

BackgroundFew studies on neonatal severe bacterial infection are available in LMICs. Data are needed in these countries to prioritize interventions and decrease neonatal infections which are a primary cause of neonatal mortality. The BIRDY project (Bacterial Infections and Antimicrobial Drug Resistant among Young Children) was initially conducted in Madagascar, Senegal and Cambodia (BIRDY 1, 2012–2018), and continued in Madagascar only (BIRDY 2, 2018–2021). We present here the BIRDY 2 project whose objectives were (1) to estimate the incidence of neonatal severe bacterial infections and compare these findings with those obtained in BIRDY 1, (2) to identify determinants associated with severe bacterial infection and (3) to specify the antibiotic resistance pattern of bacteria in newborns.MethodsThe BIRDY 2 study was a prospective community-based mother and child cohort, both in urban and semi-rural areas. All pregnant women in the study areas were identified and enrolled. Their newborns were actively and passively followed-up from birth to 3 months. Data on clinical symptoms developed by the children and laboratory results of all clinical samples investigated were collected. A Cox proportional hazards model was performed to identify risk factors associated with possible severe bacterial infection.FindingsA total of 53 possible severe bacterial infection and 6 confirmed severe bacterial infection episodes were identified among the 511 neonates followed-up, with more than half occurring in the first 3 days. For the first month period, the incidence of confirmed severe bacterial infection was 11.7 per 1,000 live births indicating a 1.3 -fold decrease compared to BIRDY 1 in Madagascar (p = 0.50) and the incidence of possible severe bacterial infection was 76.3, indicating a 2.6-fold decrease compared to BIRDY 1 in Madagascar (p < 0.001). The 6 severe bacterial infection confirmed by blood culture included 5 Enterobacterales and one Enterococcus faecium. The 5 Enterobacterales were extended-spectrum β-lactamases (ESBL) producers and were resistant to quinolones and gentamicin. Enterococcus faecium was sensitive to vancomycin but resistant to amoxicillin and to gentamicin. These pathogns were classified as multidrug-resistant bacteria and were resistant to antibiotics recommended in WHO guidelines for neonatal sepsis. However, they remained susceptible to carbapenem. Fetid amniotic fluid, need for resuscitation at birth and low birth weight were associated with early onset possible severe bacterial infection.ConclusionOur results suggest that the incidence of severe bacterial infection is still high in the community of Madagascar, even if it seems lower when compared to BIRDY 1 estimates, and that existing neonatal sepsis treatment guidelines may no longer be appropriate in Madagascar. These results motivate to further strengthen actions for the prevention, early diagnosis and case management during the first 3 days of life.

Impact of bacterial infections prior to liver transplantation on post-transplant outcomes in patients with cirrhosis

Bacterial infections are frequent in patients with cirrhosis and increase the risk of death and drop-out from liver transplant (LT) waiting list. In patients with bacterial infections, LT is frequently delayed because of the fear of poor outcomes. We evaluated the impact of pre-LT infections on post-LT complications and survival. From 2012 to 2018, consecutive patients transplanted at the Hospital of Padua were identified and classified in two groups: patients surviving an episode of bacterial infection within 3 months before LT (study group) and patients without infections before LT (control group). Post-LT outcomes (complications, new infections, survival) were collected. A total of 466 LT recipients were identified (study group n= 108; control group n= 358). After LT, the study group had a higher incidence of new bacterial (57% vs. 20%, p <0.001) and fungal infections (14% vs. 5%, p= 0.001) and of septic shock (8% vs. 2%, p= 0.004) than the control group. Along with the model for end-stage liver disease (MELD) score and alcohol-related cirrhosis, bacterial infection pre-LT was an independent predictor of post-LT infections (odds ratio= 3.92; p <0.001). Nevertheless, no significant difference was found in 1-year (88% vs. 89%, p= 0.579) and 5-year survival rates (76% vs. 75%, p= 0.829) between the study group and control group. Within the study group, no association was found between the time elapsed from infection improvement/resolution to LT and post-LT outcomes. Patients with pre-LT infections have a higher risk of new bacterial and fungal infections and of septic shock after LT. However, post-LT survival is excellent. Therefore, as soon as the bacterial infection is improving/resolving, transplant should not be delayed, but patients with pre-transplant bacterial infections require active surveillance for infections after LT. Bacterial infections increase mortality and delay transplant in patients with cirrhosis awaiting liver transplantation (LT). Little is known about the impact of adequately treated infections before LT on post-transplant complications and outcomes. The study highlights that pre-LT infections increase the risk of post-LT infections, but post-LT survival rates are excellent despite the risk. These findings suggest that physicians should not delay LT because of concerns about pre-LT infections, but instead should actively monitor these patients for infections after surgery.

Structured Immune Workup in Healthy Children With a First Episode of Severe Bacterial Infection: A 7-year Single-Center Study.

Severe bacterial infections (SBIs) in otherwise healthy children are rare and may represent an underlying impairment of the immune system, including primary immunodeficiency. However, it is unclear whether and how children should be assessed. We retrospectively analyzed data from hospital records of previously healthy children aged 3 days to 18 years with SBI, including pleuropneumonia, meningitis, and/or sepsis. Patients were diagnosed or immunologically followed up between 1 January 2013 and 31 March 2020. Among 432 children with SBI, findings could be analyzed in 360. Follow-up data were available for 265 children (74%), of whom 244 (92%) underwent immunological testing. Laboratory abnormalities were found in 51 of 244 patients (21%), with 3 deaths (1%). Fourteen children (6%) had immunodeficiency considered clinically relevant (3 complement deficiencies, 1 autoimmune neutropenia, 10 humoral immunodeficiencies), and 27 (11%) had milder humoral abnormalities or findings suggestive of delayed adaptive immune maturation. A substantial proportion of children with SBI may benefit from routine immunological testing, revealing (potentially) clinically relevant impaired immune function in 6%-17% of children. The identification of immune abnormalities allows for specific counseling of families and optimization of preventive measures, such as booster vaccinations, to avoid future SBI episodes.

Naïve T Cell-Depleted Hematopoietic Graft Combined with Solid Organ Transplantation As Strategy to Induce Tolerance By Transient Mixed Chimerism

BACKGROUND The major challenge of solid organ transplantation (SOT) is to prevent graft rejection. The chronic use of pharmacological immunosuppression has been associated with increased rates of infection, cardiovascular, metabolic, endocrine disorders, and cancer. The induction of chimerism by donor hematopoietic stem cell transplantation (HSCT) together with SOT is an active tolerance induction approach. Here, we present a new model for inducing transient mixed chimerism in 2 patients undergoing SOT employing a non-myeloablative conditioning (NMA) regimen and a partially T cell-depleted (TCD) graft consisting of CD34+ hematopoietic progenitor cells and CD45RA− memory lymphocytes. METHODS SOT and HSCT were performed at University Hospital La Paz, Madrid. Bone marrow harvesting was performed on the iliac crest and lumbar and dorsal vertebrae of the deceased donor for patient#1 and mobilized leukoapheresis from sibling donor for patient#2. First we obtained the enriched by CD34+ selection using the CliniMACS system (Miltenyi Biotec) and afterwards the CD45RA− cells were purified. Lineage-specific chimerism analysis was analyzed using quantitative real-time polymerase chain reaction. Immune cell recovery was monitored by multiparametric flow cytometry. We obtained the permission of the Organización Nacional de Trasplantes and the informed consent was obtained from the patient and donor and/or caregivers. RESULTSPatient 1 A 15-year-old boy was diagnosed with intestinal epithelial dysplasia in 2008. After two previous intestinal and multivisceral acute cellular rejections forced a third MVT. With the imptemption to induce donor tolerance, a T cell-depleted bone marrow graft from the same deceased donor was employed. Bone marrow harvesting was performed obtaining a total volume of 141 ml with 4x109 total nucleated cells. Peripheral blood was obtained after unclasping the thoracic aorta. The stem cell fraction from bone marrow was enriched by CD34+ selection, obtaining 8.75x105/kg CD34+cells/kg. Memory lymphocytes were purified and aliquots containing 1x106/kg CD3+CD45RO+ and 2.1x104/kg CD3+CD45RA+ T cells. Both products were cryopreserved. The conditioning regimen before HSCT included fludarabine and cyclophosphamide. On day 88 after MVT, we infused all the CD34+ cells and 1x106/Kg CD3+CD45RO+ T cells. The CD3+CD45RO+ T cells were also infused periodically on a monthly basis for 1 year. Donor chimerism in CD3+ T cells ranged from 0.05 to 5.1 during the first year after HSCT. We observed a peak of the percentage of regulatory T cells (Tregs). No degree of graft-versus-host disease (GvHD) was observed, and the patient became independent of total parenteral and enteral nutrition. Serial follow-up intestinal biopsies did not show any sign of immune rejection. The patient continued to receive sirolimus to maintain drug concentrations at 6 ng/ml as the only immunosuppression treatment. No signs of rejection were detected after 27 months of follow-up. Patient 2 A 49-year-old woman was diagnosed with chronic kidney failure secondary to rapidly progressive glomerulonephritis. The patient had received 3 previous kidney transplants from deceased donors. A kidney transplant from her sibling was performed in March 2021. Hematopoietic progenitor cells were obtained from mobilized peripheral blood leukapheresis. A NMA conditioning regimen employing total lymphoid irradiation (8 Gy) with antithymocyte globulin (7.5 mg/kg). Two weeks after the kidney transplantation, we infused a graft consisting of 1.27x107/kg CD34+, 4.43x106/kg CD3+CD45RO+, and 5x104/kg CD3+CD45RA+ cells. Controls for hematopoietic chimerism demonstrated the presence of transient mixed hematopoietic chimerism during the first 2 months after SOT of between 0.1% and 40% CD3+ cells. The patient continued on monotherapy with tacrolimus. Immune reconstitution analysis showed a Treg peak. The patient did not have acute rejection, GvHD, viral reactivations or episodes of bacterial infection during the 17 months of follow-up. CONCLUSIONS We describe for the first time the use of non-myeloablative conditioning and a CD45RA− T cell-depleted graft to induce transitory mixed chimerism using both hematopoietic progenitors and a solid organ coming from the same donor, for tolerance induction purposes. The patients continue to progress favorably 17 months or more after SOT, receiving immunosuppressive monotherapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Pathogen distribution and risk factors of bacterial and fungal infections after liver transplantation.

Liver transplant recipients have a high rate of postoperative infection, and identification of patients at high risk for bacterial and fungal infections will help prevent disease and improve long-term outcomes for them. This study aims to understand the composition, distribution, prognosis of bacterial and fungal infections within 2 months after liver transplantation and to analyze their risk factors. The data of pathogen composition, distribution, and prognosis of bacterial and fungal infections among liver transplant recipients in the Third Xiangya Hospital of Central South University from May 2020 to October 2021 were collected, and the risk factors for these infections were analyzed. A total of 106 episodes of bacterial or fungal infections occurred in 71.4% of liver transplant recipients (75/105). Gram-negative bacteria were the dominant pathogenic bacteria (49/106, 46.2%), followed by Gram-positive bacteria (31/106, 29.2%). The most common Gram-negative bacterium was Acinetobacter baumannii (13/106, 12.3%). The most common Gram-positive bacterium was Enterococcus faecium (20/106, 18.9%). The most common infections were pulmonary (38/105, 36.2%) and multiple site infections (30/105, 28.6%). Six (6/105, 5.7%) patients with infections died within 2 months after liver transplantation. Univariate analysis showed that the model for end-stage liver disease (MELD) score ≥25, antibiotic use within half a month before transplantation, infections within 2 months prior to transplantation, intraoperative red blood cell infusion≥8 U, indwelling urinary tract catheter ≥4 days after transplantation, and the dosage of basiliximab use ≥40 mg were associated with infections. Multivariate logistic regression analysis revealed that only infections within 2 months prior to transplantation (OR=5.172, 95% CI 1.905-14.039, P<0.01) was an independent risk factor for bacterial and fungal infections after liver transplantation. Postoperative bacterial and fungal infections were reduced in liver transplant recipients receiving basiliximab ≥40 mg (OR=0.197, 95% CI: 0.051-0.762, P<0.05). The incidence of bacterial and fungal infections is high in the early stage after liver transplantation, and the mortality after infection is significantly higher than that of non-infected patients. The most common infection is respiratory infection, and the dominant pathogens is Gram-negative bacteria. Patients infected within 2 months prior to liver transplantation are prone to bacterial and fungal infections. Standard use of basiliximab can reduce the incidence of infections after liver transplantation.

The «microbiome» of post-liver transplant complications

This paper reviews modern literature and presents a brief analysis of our own data on one of the most pressing issues in modern transplantology and, in particular, transplant hepatology – the role and place of gut-liver axis (GLA) in the early post-transplant period.Objective: to compare the correlation between gut microbiome palette and incidence of certain early postoperative complications in liver transplantation.Materials and methods. The study design is presented as a pilot, prospective, observational, double-blind study based on investigation of the composition of the microbiome residing in the large intestinal in patients that underwent orthotopic liver transplantation (OLTx). The primary cohort of patients consisted of 12 patients who underwent OLTx from a postmortem donor. To assess the gut microbiome palette, biomaterial was collected from all patients in the preand post-transplant period followed by next-generation sequencing. The study was conducted as primary study results registered under number NCT04281797.Results. In the preoperative period, differences close to statistically reliable in relation toActinobacteriawere observed in patients included in the liver transplant waiting list for cirrhosis (LC) and hepatocellular carcinoma (HCC) in cirrhosis. However, due to the pilot nature of the study, this study cohort was limited to an extremely small sample. In turn, in the post-transplant period, there was a statistically significant difference in the taxonomic range ofActinobacteria(p &lt; 0.05) between the above groups, indicating a possible effect of liver transplantation on the gut microbiome. In addition, in the early post-transplant period, there was a marked difference in the microbiome palette between patients with and without acute cellular rejection.Conclusion. GLA and the gut microbiome play a critical role in many liver diseases, and may also have a significant impact on the post-transplant period. In this regard, further research in this direction will not only characterize the predictors and risk factors of bacterial infection and rejection episodes, but will also allow us to form a completely new approach to the treatment tactics for certain complications, including through formation of a microbiota-oriented pharmacotherapy.

La thymoglobuline en traitement d’induction chez les transplantés rénaux à faible risque immunologique: une expérience marocaine

Introductionla thymoglobuline® est un anticorps polyclonal indiqué en traitement d´induction en transplantation rénale. Le but de notre travail est d´étudier l´efficacité de la thymoglobuline® en traitement d´induction chez des transplantés rénaux à faible risque immunologique.Méthodesil s´agit d´une étude rétrospective entre Janvier 2012 et Septembre 2017. On a inclus les patients à faible risque immunologique, défini par l´absence de transplantation antérieure et d´anticorps spécifiques du donneur (DSA), qui ont reçu un traitement d´induction à base de thymoglobuline®. On a étudié les caractéristiques démographiques et cliniques, les paramètres biologiques ainsi que les complications post transplantation rénale.Résultatsnous avons inclus 55 patients transplantés rénaux avec un suivi moyen de 38 ± 16 mois. L´âge moyen était de 39,1 ± 12,1 ans avec une prédominance masculine (58,2%). Aucun patient n´avait de DSA avant la greffe. La dose cumulative de la thymoglobuline® était de 4,26 ± 0,87 mg/kg avec une durée moyenne de 5 ± 0,82 jours. La déplétion lymphocytaire était maximale au premier jour de la perfusion. Nous avons recensé 3 cas de reprise retardée de la fonction du greffon, au moins un épisode d´infection bactérienne chez 56,4% de nos patients, 7 cas d´infection à cytomégalovirus (CMV) (12,7%) et 2 cas de maladie à CMV (3,6%). La survie du greffon était notée chez tous nos patients avec un taux de créatinine sérique moyen à 11,7 ± 3,6 mg/l au cours de la dernière consultation.Conclusionbien qu´elle ne soit pas indiquée en première intention chez les patients à faible risque immunologique, la thymoglobuline® peut néanmoins être prescrite à dose plus faible, avec une efficacité similaire et sans exposition à un risque de rejet plus élevé.

Diagnostic value of procalcitonin for bacterial infections in patients undergoing hemodialysis: a systematic review and meta-analysis

Background The diagnostic value of procalcitonin (PCT) in patients undergoing hemodialysis (HD) remains unclear. Methods We searched multiple databases (PubMed, EMBASE, and Cochrane Library) for studies published through August 2021 that evaluated the diagnostic performance of PCT in patients undergoing HD and having suspected bacterial infections. The bivariate fixed effects model was used to calculate pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and summary receiver operating characteristic (SROC) curves. Results We identified a total of 1799 studies, of which seven diagnostic studies comprised 1444 patients and 430 bacterial infection episodes. Bivariate pooled sensitivity and specificity for PCT were 0.90 (95% CI: 0.85–0.94) and 0.83 (95% CI: 0.56–0.95), respectively. Furthermore, pooled DOR, PLR, NLR, and area under the curve (AUC) were 47 (95% CI: 11–209), 5.4 (95% CI: 1.7–16.9), 0.12 (95% CI: 0.07–0.20), and 0.92 (95% CI: 0.90–0.94), respectively. We also compared the diagnostic accuracy of PCT and C-reactive protein (CRP), and our results showed that the diagnostic accuracy parameters for PCT were significantly higher than those for CRP. Conclusions PCT is a useful marker for diagnosis of bacterial infections in patients undergoing HD at a cutoff value of 1.5 ng/ml.

Implementation and impact of an antibiotic control program and multidrug-resistant bacterial colonization in a liver transplant unit.

infections by multidrug-resistant bacteria are a major cause of morbidity and mortality in transplant patients. a retrospective single-center study was performed to evaluate the implementation of an Antimicrobial Treatment Optimization Program (PROA) on multidrug-resistant bacteria colonization and infection after liver transplant (LT). colonization by multidrug-resistant bacteria and infections during the first year after a liver transplant were analyzed in a group of 76 transplanted patients in two stages, before and after PROA (2016-2019). Clinical variables related to infection, readmissions and survival one year after the liver transplant were analyzed. there was good adherence to the PROA. Infection was the most frequent cause for readmission during the first year after the liver transplant. Incidence of infections was similar during both periods (mean of 1.25 and 1.5 episodes of bacterial infection per patient/year, respectively) with 19 bacterial infectious episodes, six by hospital-acquired multidrug-resistant and extensively drug-resistant (MDR-XDR) bacteria in the pre-PROA stage, and 18 bacterial infectious episodes, five by MDR-XDR in the post-PROA stage. A 37 % decrease of post-TH of rectal colonization by MDR-XDR after liver transplant was observed during 2019. epidemiological surveillance policies and antibiotic optimization are key to control the increase of colonization and infection by multidrug-resistant bacteria in liver transplant units. Long-term studies are needed to better evaluate the impact of these programs.

Antibacterial and Antifungal Activities of Ethiopian Medicinal Plants: A Systematic Review.

Background: Podoconiosis and lymphatic filariasis are the most common causes of lower limb lymphoedema in the tropics. Many sufferers experience frequent painful episodes of acute bacterial infection. Plant based traditional medicines are used to treat infections in many countries and are culturally established in Ethiopia. Ethiopian medicinal plants found to have antibacterial and antifungal activities were reviewed with the aim of increasing information about the treatment of wound infections in patients with lymphoedema. Methods: This study collates data from published articles on medicinal plants with antibacterial and antifungal activities in Ethiopia. A systematic search of Scopus, EMBASE, PUBMED/MEDLINE and Google Scholar was undertaken. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed. The protocol was registered on PROSPERO with registration number CRD42019127471. All controlled studies of in vitro antibacterial and antifungal activities were considered. All articles containing the descriptors published until June 28, 2019 were included. The outcome was measured as percent inhibition of microbial growth. For quality assessment of individual in vitro studies, OECD guidelines and the WHO-Good Laboratory Practice (GLP) handbook were used. Results: Seventy-nine studies met the inclusion criteria. A total of 150 plant species and three compounds had been tested against 42 species of bacteria, while 43 plant species had been tested against 22 species of fungus. Conclusion: Materials derived from several Ethiopian medicinal plants have been shown to have promising activity against a variety of bacteria and fungi. Those derived from Azadiractha indica A. Juss. and Lawsonia inerms L. are the most extensively studied against a wide range of gram-negative and positive bacteria, and fungal species.

The role of prophylactic antibiotics in hepatitis B virus-related acute-on-chronic liver failure patients at risk of bacterial infection: a retrospective study

BackgroundAcute-on-chronic liver failure (ACLF) is characterized by an excessive systemic inflammatory response and organ failure and has high mortality. Bacterial infections (BIs) worsen the clinical course of ACLF and carry a poor prognosis in ACLF patients. The efficacy of third-generation cephalosporins has been challenged in recent years. The aim of this study was to characterize the difference between ACLF patients with and without BIs and to provide a reference for medical intervention.MethodsA total of 140 patients with hepatitis B virus-related ACLF (HBV-ACLF) hospitalized at the Department of Infectious Diseases, Huashan Hospital, Fudan University (Shanghai, China) between May 2013 and January 2020 were enrolled. Mann-Whitney U test was used to compare the baseline characteristics of HBV-ACLF patients with and without BIs. Univariate and multivariate analyses were performed to find predictors of BIs. The characteristics of BIs and the role of prophylactic antibiotics were profiled.ResultsA total of 97 episodes of BIs occurred in patients during the course of HBV-ACLF. Patients with and without BIs differed in clinical characteristics. The incidence of BIs showed a positive correlation with the ACLF grade (P = 0.003) and the clinical course (P = 0.003). The 90-day transplant-free survival of patients with BIs was lower than those without BIs (P < 0.0001). Patients administered prophylactic antibiotics showed a lower incidence of BIs and had a higher transplant-free survival probability than those who did not (P = 0.046). No statistical differences in antibiotic efficacy between third-generation and other antibiotics were observed (P = 0.108).ConclusionsBIs affected the clinical course and prognosis of patients with HBV-ACLF. Prophylactic antibiotics were of potential clinical importance in the prevention of BIs and improving the clinical course and prognosis in HBV-ACLF patients. Third-generation cephalosporins were qualified for use in antibiotic prophylaxis.

Humoral Immunodeficiency and Immune Globulin Replacement Therapy (IGRT) Usage in DiGeorge Syndrome.

An analysis of patients in the United States Immunodeficiency Network (USIDNET) registry previously described a discordance in the reported prevalence of humoral immune deficiency in patients with DiGeorge syndrome (DGS) and its treatment. The primary purpose of this study is to evaluate the rates of humoral immunodeficiency and immune globulin replacement therapy (IGRT) use in patients with DiGeorge syndrome in the USIDNET registry as of September 2016, and to correlate IGRT use with prior infections and laboratory evidence of immune deficiency. Current patients in the USIDNET registry with DGS were identified. Patients who were treated with immune globulin replacement therapy (IGRT) were compared with those who were untreated with respect to their laboratory findings and clinical history. Four hundred seventy-three patients were identified. The use of IGRT in patients with DGS has increased over time from 3 to 6.6%. IGRT was more common in patients with humoral immune deficiency (18.2% of those with hypogammaglobulinemia, 39.1% of those with documented low vaccine titers), but most patients with evidence of humoral immune deficiency remain untreated with IGRT. Patients treated with IGRT were more likely to have experienced episodes of pneumonia, sepsis, and bacterial skin infections (p < 0.01 for all). Humoral immune deficiencies were more common among patients with DGS than previously reported. IGRT was used most commonly in patients with DGS who demonstrated frequent or severe bacterial infections. There is still a significant deficit between those with DGS who have laboratory evidence of a humoral immune deficiency and those being treated for it.

Pneumococcal Serotype-specific Opsonophagocytic Activity in Interleukin-1 Receptor-associated Kinase 4-deficient Patients.

The antibody response after pneumococcal vaccines and their effectiveness against invasive pneumococcal disease (IPD) in patients with interleukin-1 receptor-associated kinase 4 (IRAK4) deficiency have not been fully evaluated. Here, we evaluated pneumococcal serotype-specific opsonophagocytic activity (OPA) in IRAK4-deficient patients along with their clinical course. We investigated 6 IRAK4-deficient patients in Japan, whose attending physicians could be contacted. We performed OPA measurements using stored and more recent serum samples obtained from these patients. All patients had received pneumococcal vaccination. Among the 3 patients who had IPD, 2 had an episode of pneumococcal meningitis and the other developed pneumococcal bacteremia 3 years after the occurrence of pneumococcal meningitis. Only one episode of invasive bacterial infection was caused by a Streptococcus pneumoniae vaccine-type strain. An increased opsonization index was found in the sera after vaccination for all IRAK-deficient patients, including when the 23-valent pneumococcal polysaccharide vaccine was used. A significant increase in levels of OPA against most of the pneumococcal vaccine antigens was observed for all IRAK4-deficient patients. However, IPD could not be prevented by pneumococcal vaccination alone. Therefore, adequate prophylaxis should be provided with antibiotics at least until 8 years of age, along with regular immunoglobulin therapy, particularly during the infantile period.

High mortality associated with gram-negative bacterial bloodstream infection in liver transplant recipients undergoing immunosuppression reduction.

BACKGROUNDImmunosuppression 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.AIMTo assess the effect of temporary IS withdrawal on 30 d mortality of LT recipients presenting with severe infection.METHODSA 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.RESULTSSeventy-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. CONCLUSIONIS 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.IS

Statin use and risk of severe bacterial infection in a population living with HIV: prospective cohort study of the ANRS CO3 Aquitaine Cohort 2000–2018

ObjectivesBacterial infections remain one of the main causes of morbidity and death in people living with HIV (PLHIV) in the most recent years. Several studies have demonstrated a protective effect of statins in the primary prevention of bacterial infections in other immunocompromised populations, but this effect remains controversial. The objective of this study was to evaluate the effect of statin use on the occurrence of a first episode of severe bacterial infection (SBI) in PLHIV in the ANRS CO3 Aquitaine cohort between 2000 and 2018. MethodsAll individuals included in the prospective ANRS CO3 Aquitaine cohort who had at least two follow-up visits between 2000 and 2018 were included. The primary endpoint was the occurrence of a first episode of bacterial infection leading to hospitalization of ≥48 hours or death. Statin exposure was updated during follow-up. Marginal Cox structural models were developed to consider the potential indication bias and time-dependent confusion. Numerous sensitivity analyses were carried out. ResultsIn this study 51 658 person-years were followed. The overall incidence of a first episode of SBI was 12.4/1000 person-years. No effect of statins on the occurrence of SBI was demonstrated when subjects were considered on statins throughout their follow-up after treatment initiation (HR = 0.97; 95%CI: 0.75–1.25). The results were similar for the effect of statins on the risk of pneumonia and for all sensitivity analyses. ConclusionIn this large cohort of PLHIV with 18 years of follow-up and a high risk of severe infections, we found no effect of statins on the risk of occurrence of SBI or pneumonia.

Neutropenia resulting from high-dose intravenous immunoglobulin in dermatological patients.

Current guidelines recommend high-dose intravenous immunoglobulin (IVIG) as a rescue therapy to treat severe cutaneous autoimmune disorders. Data on IVIG-induced hematological adverse events are limited in dermatological patients. We assessed the incidence and clinical implications of IVIG-induced neutropenia. Patients who received one or several cycles of IVIG between 2014 and 2019 were retrospectively evaluated. IVIG was given according to standardized infusion protocols. Daily differential blood counts were performed. Information on clinical baseline data, dermatological diagnosis, immunosuppressive pre-treatment, and IVIG-related adverse events was retrieved from patient files. Seventeen patients received 106 IVIG treatment cycles. Neutrophil counts below 1,500/μL were documented during 36 (34.0%) cycles, and neutrophils fell below 1,000/μL in 14 (13.2%) cases. The average drop of neutrophils from day one (pre-dose) to days 2 and 3 of IVIG therapy was statistically significant (p=0.006, and p=0.002, respectively) despite correction for hemodilution, and so was a slight decrease of thrombocytes (p=0.029, and p=0.011, respectively). Four patients developed seven episodes of bacterial infections during or immediately after IVIG therapy. IVIG-induced neutropenia is frequent in dermatological patients. A risk of secondary bacterial infections cannot be excluded.

High prevalence of multidrug-resistant gram-negative bacterial infection following pediatric liver transplantation.

Bacterial infection has been identified as one of the most significant complications of liver transplantation (LT). Multidrug-resistant (MDR) gram-negative bacteria (GNB) infection remains problematic issue following LT in the adults. However, data in children are scarce. We aimed to examine the prevalence and associated factors of MDR-GNB infection among pediatric LT recipients.We performed a single-center retrospectively study of 118 children who underwent LT between January 2010 and December 2018. Data on the prevalence, clinical characteristics, types, and sites of MDR-GNB infection within 3 months after LT as well as the treatment outcomes were collected. Multidrug resistance was defined as acquired non-susceptibility to at least 1 agent in 3 or more antibiotic classes.In total, 64 (53.7%) patients developed 96 episodes of culture-proven bacterial infection with 93 GNB isolates. Moreover, there were 58 (62.4%) MDR-GNB isolates, with a predominance of Klebsiella pneumoniae (32.7%), Escherichia coli (31%), and Pseudomonas aeruginosa (10.3%). Interestingly, 10 (17.2%) isolates were determined to be carbapenem-resistant Enterobacteriaceae. The median time to MDR-GNB infection was 9 (interquartile range: 5-33) days. The most common type of infection was intra-abdominal infection (47.9%). In the multivariate analysis, the significant variables associated with post-LT MDR-GNB infection include exposure to third-generation cephalosporins (hazard ratio [HR]: 2.16, P = .023), operative time (hazard ratio [HR] 1.20, P = .009), and length of intensive care unit stay (HR 1.03, P = .049). With a focus on carbapenem-resistant Enterobacteriaceae infection, a pediatric end-stage liver disease score >21 was the only significant 6 variable in the multivariate analysis (HR 11.48, P = .024). The overall 3-month mortality rate was 6.8%.This study has highlighted the high prevalence rate of MDR-GNB infection after pediatric LT. Therefore, caution on the emergence of MDR-GNB infection should be paid in at-risk children. Moreover, knowledge regarding the prevalence of MDR-GNB infection and resistant patterns is essential for guideline development to prevent and minimize the risk of MDR-GNB infection in this group of patients.