Gut microbiota trajectory in ß-thalassemia major children who underwent allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The gut microbiota of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) changes, leading to complications such as acute graft-versus-host disease (GVHD). This study aimed to evaluate the human microbiota composition before and after HSCT in ß-thalassemia major (ß-TM) children. METHOD: Twenty-two ß-TM children who received allo-HSCT between December 2018 and March 2020 were enrolled. They were followed up for more than 100 days after HSCT, and their gut microbiota information and disease data were recorded at five-time points. RESULTS: The dominant bacteria were Bacteroidetes and Firmicutes at the phylum level and Lachnospiraceae at the family level before and after HSCT. In the differential analysis, Ruminococcaceae constantly decreased after HSCT. Besides, Rothia mucilaginosa was the most abundant 2 months after HSCT compared to before it. Additionally, GVHD patients presented decreased levels of Bacteroidetes compared to those without GVHD. Moreover, Blautia levels significantly decreased in critically ill GVHD patients. CONCLUSION: The gut microbiota of the 22 ß-TM children showed a clear trend of destruction and reconstruction within 100 days after HSCT. The extra-oral infections and inflammations of Rothia mucilaginosa, a Gram-positive bacterium of the normal oropharyngeal tract microbiota, might play an important role in the recovery process of HSCT. Finally, decreased Bacteroidetes levels were associated with GVHD onset.

Identification of different proteins binding to Na, K-ATPase α1 in LPS-induced ARDS cell model by proteomic analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by refractory hypoxemia caused by accumulation of pulmonary fluid, which is related to inflammatory cell infiltration, impaired tight junction of pulmonary epithelium and impaired Na, K-ATPase function, especially Na, K-ATPase α1 subunit. Up until now, the pathogenic mechanism at the level of protein during lipopolysaccharide- (LPS-) induced ARDS remains unclear. METHODS: Using an unbiased, discovery and quantitative proteomic approach, we discovered the differentially expressed proteins binding to Na, K-ATPase α1 between LPS-A549 cells and Control-A549 cells. These Na, K-ATPase α1 interacting proteins were screened by co-immunoprecipitation (Co-IP) technology. Among them, some of the differentially expressed proteins with significant performance were identified and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Data are available via ProteomeXchange with identifier PXD032209. The protein interaction network was constructed by the related Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Several differentially expressed proteins were validated by Western blot. RESULTS: Of identified 1598 proteins, 89 were differentially expressed proteins between LPS-A549 cells and Control-A549 cells. Intriguingly, protein-protein interaction network showed that there were 244 significantly enriched co-expression among 60 proteins in the group control-A549. while the group LPS-A549 showed 43 significant enriched interactions among 29 proteins. The related GO and KEGG analysis found evident phenomena of ubiquitination and deubiquitination, as well as the pathways related to autophagy. Among proteins with rich abundance, there were several intriguing ones, including the deubiquitinase (OTUB1), the tight junction protein zonula occludens-1 (ZO-1), the scaffold protein in CUL4B-RING ubiquitin ligase (CRL4B) complexes (CUL4B) and the autophagy-related protein sequestosome-1 (SQSTM1). CONCLUSIONS: In conclusion, our proteomic approach revealed targets related to the occurrence and development of ARDS, being the first study to investigate significant differences in Na, K-ATPase α1 interacting proteins between LPS-induced ARDS cell model and control-A549 cell. These proteins may help the clinical diagnosis and facilitate the personalized treatment of ARDS.

A natural halogenated fluoride adenosine analog 5'-fluorodeoxy adenosine induced anticolon cancer activity in vivo and in vitro.

Adenosine (ADO) and its analogs have been introduced into the anticancer clinical trials, especial for the ADO derivatives with fluoride. The biosynthesis of fluorinase produces a fluorine-containing ADO analog 5'-fluorodeoxy adenosine (5'-FDA). The toxicity and application of 5'-FDA has not been evaluated, which limits the application of ADO analogs. In order to study its potential mechanism, we carried out the following experiments. In our research, 5'-FDA displayed good antitumor activity in colon cancer cells and two colon cancer models. As a result, 5'-FDA concentration-dependently inhibited the proliferation, migration, and invasion in colon cancer cells through its proapoptosis and cell cycle arrest pathway. Furthermore, 5'-FDA inhibited the growth of colon cancer and its pulmonary metastasis in CT26 inbred mice without affecting their body weight. It was found that 5'-FDA remarkably increased the protein levels of Caspase 3 and cleaved-Caspase 9 and decreased Cyclin A2 and CDK2 via the regulation of p53 signaling pathway, and increased the protein levels of Caspase 8 and cleaved-Caspase 8 which participated in apoptosis pathway. All in all, 5'-FDA displayed excellent therapeutic effects on colon cancer and its pulmonary metastasis. We believed that our study provided a theoretical basis for further preclinical research of 5'-FDA in the treatment of cancer.

The Wee1 kinase inhibitor MK1775 suppresses cell growth, attenuates stemness and synergises with bortezomib in multiple myeloma.

Multiple myeloma stem-like cells (MMSCs) are responsible for initiation and relapse, though novel treatment paradigms that effectively eradicate MMSCs are yet to be developed. Selective inhibition of the cell cycle regulatory kinase Wee1 by MK1775 is being explored as a potential anti-cancer therapeutic. We report that higher expression of Wee1 is correlated with poor survival in multiple myeloma (MM). The MM models and patient-derived CD138+ plasma cells are particularly sensitive to the growth-inhibitory effects of the Wee1 inhibitor MK1775. MK1775 induces Mus81-Eme1 endonuclease-mediated DNA damage in S-phase cell cycle that results in a blockade of replication and then apoptosis. Furthermore, MK1775 strongly suppresses the features of stemness in vitro, in vivo and in primary CD138+ cells by decreasing ALDH1+ cell fraction and the expression of ALDH1. In addition, co-treatment of MK1775 with bortezomib is synergistic in vitro and in vivo. Bortezomib, although it enhances ALDH1+ cells, when combined with MK1775 abrogates this stimulatory effect on stemness. Considering MM as an invariably incurable malignancy due to the presence of heterogenic myeloma stem-like cells, our study presents inhibition of Wee1 as a promising targeted therapy for MM and provides a compelling rationale to further investigate the activity of MK1775 against myeloma in clinical settings.

Risk Factors for Acquisition of Carbapenem-Resistant Klebsiella pneumoniae and Mortality Among Abdominal Solid Organ Transplant Recipients with K. pneumoniae Infections.

BACKGROUND For abdominal solid organ transplant (ASOT) recipients, infection with Klebsiella pneumoniae, particularly carbapenem-resistant K. pneumoniae (CRKP), can be life-threatening. The aims of this study were to characterize the risk factors associated with acquisition of CRKP and 90-day crude mortality among patients. MATERIAL AND METHODS In our cohort study, we retrospectively reviewed 68 K. pneumoniae-infected transplant recipients, studied their demographics, clinical manifestations, microbiology, and outcomes, and determined the risk factors associated with the occurrence of CRKP and crude mortality due to K. pneumoniae infections. RESULTS Sixty-eight ASOT recipients (5.4%) experienced 78 episodes of K. pneumoniae infection. Among these, 20 patients (29.4%) died. The independent risk factors associated with mortality were multiple infected organs or sites (odds ratio=22.034, 95% confidence intervals=4.348-111.653, P=0.001) and septic shock (odds ratio=27.090, 95% confidence intervals=1.841-398.512, P=0.016). Risk factors associated with acquisition of CRKP were multiple infected organs or sites (odds ratio=3.056, 95% confidence intervals=1.091-8.556, P=0.033). CONCLUSIONS K. pneumoniae infections, especially CRKP, frequently occurred among ASOT recipients, with a high mortality rate. Multiple infected organs or sites and septic shock were predictors of crude mortality caused by K. pneumoniae infections, while CRKP infections were associated with multiple infected organs or sites. Greater efforts are needed towards improved antibiotic administration, early diagnosis and precise treatment, recognition of septic shock, and reduced length of hospitalization.

Revision of the medically relevant species of the yeast genus Diutina.

Diutina (Candida) rugosa is emerging as a causative agent of human infections. Recently some close relatives have been described, that is, D. mesorugosa, D. pseudorugosa, and D. neorugosa, some of which have also been implicated in human infection. Phylogenetic relationships of 24 clinical isolates of the D. rugosa complex are reconstructed using multilocus sequence analysis of five housekeeping genes, supplemented with phenotypic studies of CandiSelect™ 4 Agar and nutritional physiology. Diutina mesorugosa could not meaningfully be distinguished from D. rugosa and is regarded as a synonym. Diutina neorugosa and D. pseudorugosa represent separate, distantly related species within the genus Diutina, but have as yet not been encountered in clinical settings.

Inulin enhanced rifaximin-inhibited colon cancer pulmonary metastasis by flora-regulated bile acid pathway.

Inulin as a natural polysaccharide regulates intestinal microorganisms, and improves the immune and gastrointestinal function. In order to explore the effect of inulin on pulmonary metastasis of colon cancer, we set up a CT26 injected pulmonary metastatic model. The results showed that inulin used alone did not improve pulmonary metastasis of colon cancer, while inulin combined with rifaximin significantly prolonged the survival time of mice, and inhibited pulmonary metastasis compared with model and inulin groups. Inulin treatment increased the abundance of harmful bacteria such as Proteobacteria and Actinobacteria, while combined treatment decreased their abundance and increased the abundance of beneficial bacteria containing Firmicutes and Eubacterium which belonged to the bile acid-related bacteria. The combination treatment decreased the content of primary bile acids and secondary bile acids in the feces of mice, especial for DCA and LCA which were the agonists of TGR5. Furthermore, the combination treatment reduced the mRNA expression of the TGR5, cyclin dependent kinase 4, cyclin 1 and CDK2, increased the mRNA expression of p21 in the lung, down-regulated the level of NF-κB p65, and up-regulated the level of TNF-α compared with the model group. The above may be the reason for the better use of the combination treatment.

Litchi procyanidins inhibit colon cancer proliferation and metastasis by triggering gut-lung axis immunotherapy.

Litchi chinensis seed, as a valuable by-product of the subtropical fruit litchi (Litchi chinensis Sonn.), has been confirmed to be rich in procyanidins (LPC). The anticarcinogenic properties of procyanidins has been primarily attributed to their antioxidant and anti-inflammatory activities. However, there is a comparative paucity of information on if and how LPC inhibits colon cancer. Here, LPC significantly inhibited CT26 colon cancer cells proliferation and metastasis in vivo and in vitro. In CT26 lung metastatic mice, the anti-metastatic effect of LPC relied on its regulation of gut microbiota such as increase of Lachnospiraceae UCG-006, Ruminococcus, and their metabolites such as acetic acid, propionic acid and butyric acid. In addition, LPC significantly inhibited CT26 colon cancer cells metastasis through increasing CD8+ cytotoxic T lymphocytes infiltration and decreasing the number of macrophages. Antibiotics treatment demonstrated that the therapeutic effect of LPC depended on the gut microbiota, which regulated T cells immune response. Taken together, LPC had strong inhibitory effects on colon cancer pulmonary metastasis by triggering gut-lung axis to influence the T cells immune response. Our research provides a novel finding for the utilization of procyanidins in the future, that is, supplementing more fruits and vegetables rich in procyanidins is beneficial to the treatment of colon cancer, or it can be used as an adjuvant drug in clinical anti-tumor immunotherapy.

Case Report: Response to ALK-TKIs in a metastatic lung cancer patient with morphological heterogeneity and consistent molecular features.

Lung adenosquamous carcinoma (ASC) is a rare heterogeneous tumor containing two distinct components of adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). The limited biopsy sampling of the primary tumor might have overlooked either the ADC component or the SQCC component, resulting in a misdiagnosis of pure histology. Genotyping for driver mutations is now routinely performed in clinical settings to identify actionable oncogenic mutations and gene arrangements. Additionally, somatic mutations can potentially serve as a marker of clonal relationships. We report a rare case of ASC lung cancer, in which metastases were identified as ADC, while the primary was initially diagnosed as SQCC based on a fibrobronchoscope brush biopsy. The primary and metastatic tumors shared ALK rearrangement and other mutations support they were derived from a single clone origin. Our hypothesis is that the primary tumor contained a minor component of ADC that was not present in the histologic sections of lung biopsy. After sequential ALK-tyrosine kinase inhibitor (TKI) targeted therapy, both the patient's primary lung tumor and the site of metastatic subcutaneous nodules decreased in size, with the metastatic sites demonstrating more noticeable shrinkage. However, after 11 months of targeted therapy, the patient was found to be resistant to ALK-TKIs. Subsequently, the patient's respiratory status deteriorated rapidly, and a cycle of immunotherapy and chemotherapy did not show efficacy. To the best of our knowledge, this is a very rare case of lung ASC, disseminated metastasizing, with distinct morphology between the primary and metastases. Different therapeutic effects of ALK-TKIs were observed in two different morphological sites, with the metastatic cutaneous lesions shrinking more significantly than the primary lung lesions, though they both harbor the same EML4-ALK rearrangement. This case may provide diagnostic and therapeutic insights into lung ASC.

Lipid metabolism contribute to the pathogenesis of IgA Vasculitis.

BACKGROUND AND OBJECTIVES: The underlying mechanism of IgA vasculitis (IgAV) and IgA vasculitis with nephritis (IgAVN) remains unclear. Therefore, there are no accurate diagnostic methods. Lipid metabolism is related to many immune related diseases, so this study set out to explore the relationship of lipids and IgAV and IgAVN. METHODS: Fifty-eighth patients with IgAV and 28 healthy controls were recruited, which were divided into six separate pools to investigate the alterations of serum lipids according to the clinical characteristics: healthy controls group (HCs) and IgAV group (IgAVs), IgAVN group (IgAV-N) and IgAV without nephritis group (IgAV-C), initial IgAV group (IgAV0) and IgAV in treatment with glucocorticoids group (IgAV1). RESULTS: 31 identified lipid ions significantly changed in IgAVs with p < 0.05, variable importance of the projection (VIP) > 1 and fold change (FC) > 1.5. All these 31 lipid ions belong to 6 classes: triacylglycerols (TG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine, ceramide, and lysophosphatidylcholine. TG (16:0/18:1/22:6) +NH4 over 888875609.05, PC (32:1) +H over 905307459.90 and PE (21:4)-H less than 32236196.59 increased the risk of IgAV significantly (OR>1). PC (38:6) +H was significantly decreased (p < 0.05, VIP>1 and FC>1.5) in IgAVN. PC (38:6) less than 4469726623 conferred greater risks of IgAV (OR=45.833, 95%CI: 6.689~341.070). CONCLUSION: We suggest that lipid metabolism may affect the pathogenesis of IgAV via cardiovascular disease, insulin resistance, cell apoptosis, and inflammation. The increase of TG(16:0/18:1/22:6) + NH4, and PC(32:1) + H as well as PE (21:4)-H allow a good prediction of IgAV. PE-to-PC conversion may participate in the damage of kidney in IgAV. PC (38:6) + H may be a potential biomarker for IgAVN.

Polyphenol-Rich Extract from Litchi chinensis Seeds Alleviates Hypertension-Induced Renal Damage in Rats.

Litchi chinensis seed is a valuable byproduct of the subtropical fruit litchi (L. chinensis Sonn.), whose extract (LSE) has been confirmed to ameliorate dyslipidemia, hyperglycemia, and oxidative stress caused by type 2 diabetes. However, if LSE exerts an effect on anti-hypertension and hypertensive renal damage remains unknown. In this study, 13 polyphenols and one fatty acid were identified by UPLC-Q/TOF-MS. Network pharmacological analysis revealed that the therapeutic effects of LSE may be involved in multitargets and multipathways, such as the TNF signaling pathway, interleukin (IL)-6-mediated signaling pathway, NF-kappa B signaling pathway, removal of superoxide radicals, negative regulation of blood pressure, and so forth. Moreover, spontaneously hypertensive rats (SHRs) were daily gavaged with LSE (60 mg/kg) for 10 weeks. LSE remarkably reduced systolic blood pressure (SBP). The hypertension-induced renal damage was improved by suppressing inflammation and oxidative stress, which was consistent with the prediction of network pharmacology. In addition, LSE treatment remarkably increased the relative abundances of Lactobacillus and the production of short-chain fatty acids in the intestine. Our study indicated that a byproduct of litchi, namely, litchi seed, may be effective in reducing SBP and alleviating hypertensive renal damage.

Epidemiology, Susceptibility, and Risk Factors Associated with Mortality in Carbapenem-Resistant Gram-Negative Bacterial Infections Among Abdominal Solid Organ Transplant Recipients: A Retrospective Cohort Study.

INTRODUCTION: Carbapenem-resistant gram-negative bacteria (CR-GNB) can cause life-threatening infections among abdominal solid organ transplantation (ASOT) recipients. This study aimed to investigate the epidemiology and drug susceptibility of CR-GNB pathogens and identity the risk factors associated with 90-day crude mortality of CR-GNB infections among ASOT recipients. METHODS: We retrospectively reviewed the clinical characteristics, drug resistance rate, and risk factors associated with mortality in CR-GNB infections among ASOT recipients between August 1, 2013, and August 1, 2020. The Cox regression model was performed to identify the independent risk factors for mortality. RESULTS: During the 8-year period, CR-GNB infections occurred in 153 of 1452 (10.5%) recipients, and 23 of 153 (15.0%) patients died. The most common pathogen was Acinetobacter baumannii (n = 47). The drug resistance rate of CR-GNB pathogens was relatively low to tigecycline (33.3%) and high to other categories (> 60%). There was a significant increasing trend in drug resistance to tigecycline as time went on (from 24 to 40%, P = 0.04). The independent risk factors for mortality were mechanical ventilation (hazard ratio 7.40, 95% confidence interval 2.69-20.38, P < 0.001), septic shock (hazard ratio 7.41, 95% confidence interval 2.86-19.23, P < 0.001), and platelet count < 50,000/mm3 (hazard ratio 4.00, 95% confidence interval 1.49-10.76, P = 0.006). CONCLUSION: CR-GNB is widespread with high prevalence and mortality rates among ASOT recipients. Mechanical ventilation, septic shock, and low platelet count represent three independent risk factors related to the mortality of ASOT recipients with CR-GNB infection. We suggest that tigecycline may be used under rigorous management because of the significant increasing risk of drug resistance.

Integrated Analyses of Gut Microbiome and Host Metabolome in Children With Henoch-Schönlein Purpura.

Recent studies have shown that intestinal microbes and metabolites are involved in the pathogenesis of many diseases. However, whether and how they are related to Henoch-Schönlein purpura (HSP) has yet to be understood. This work is designed to detect gut microbes, intestinal and serum metabolites in children with HSP, trying to discover the etiology and pathogenesis of HSP. A total of 86 children were recruited in this study, namely, 58 children with HSP (HSP group) and 28 healthy children as control groups (CON group). 16S rDNA amplicon sequencing technology and UPLC-QTOF/MS non-targeted metabolomics analysis were used to detect the intestinal microbes and metabolites, and also multi-reaction monitoring technology for detecting serum arachidonic acid (AA) and its metabolites. Then, correlation analysis was performed to explore the possible interaction between the differential gut microbes and metabolites. As a result, at the microbiota family level, the CON group had an advantage of Coriobacteriaceae while the HSP group had a dominant Bacteroidaceae. Five kinds of bacteria in the HSP group were significantly enriched at the genus level, and seven kinds of bacteria were significantly enriched in the CON group. A total of 59 kinds of gut metabolites significantly differ between the two groups, in which most are lipids and peptides. Spearman correlation analysis showed that Bacteroides, Dialister, and Agathobacter were associated with unsaturated fatty acids, especially AA metabolism. Then, we tested the AA related metabolites in serum and found thromboxane B2, leukotriene B4, prostaglandin D2, 9S-hydroxyoctadecadienoic acid, and 13S-hydroxyoctadecadienoic acid significantly changed. In conclusion, children with HSP had dominant Bacteroidaceae and decreased Coriobacteriaceae in the family level of gut microbes, and also lipids and peptides changed most in the gut metabolites. Our data suggested that the biosynthesis and metabolism of unsaturated fatty acids, especially AA and its metabolites, might participate in the occurrence and development of HSP.

Friend or foe? The roles of inulin-type fructans.

Inulin-type fructans (ITFs) as functional fructans and soluble dietary fiber are a mixture of inulin, oligofructose and fructooligosaccharide with ß configuration. They are modified by gut microbiota at the end of ileum, subsequently, improve digestive system, metabolic syndrome, immune system and inflammatory diseases, and prevent against infection and cancer. However, it has been reported that inadequate consumption of ITFs aggravates the development of non-alcoholic fatty liver disease, results in gastrointestinal symptoms, liver cancer and intestinal inflammation. Therefore, this review summarizes the health benefits, pharmaceutical applications and safety evaluation of ITFs, which would direct their rational applications.

Identification of N-methylaniline based on azo coupling reaction by combining TLC with SERRS.

The objective of this study was to establish a novel method for the determination of N-methylaniline (NMA) based on azo coupling reaction in infant pacifiers prepared with food contact silicone materials by combining thin layer chromatography (TLC) with surface-enhanced resonance Raman scattering (SERRS). TLC was used to separate the azo reaction products to confirm the component spot of azo compound, then the spot of azo compound mixed with silver sol on the TLC plate was qualitatively detected by SERRS. The limit of detection (LOD) of the method is as low as 0.50 ppm for NMA. The influence of sample matrix about the TLC-SERRS detection of NMA was investigated by experiment of simulated positive sample, and the NMA in infant pacifiers exposed to silica gel products was detected. The method of TLC-SERRS for the determination of NMA in infant pacifiers prepared with food contact silicone materials was established, and the real samples were detected. Compared with the methods ever reported, the method has the advantages of high sensitivity, specificity and low cost. It provides a new reference method for establishing a safety system for food contact silicone materials.

Correlation Analysis between Gut Microbiota and Metabolites in Children with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune-mediated diffuse connective tissue disease characterized by immune inflammation with an unclear aetiology and pathogenesis. This work profiled the intestinal flora and faecal metabolome of patients with SLE using 16S RNA sequencing and gas chromatography-mass spectrometry (GC-MS). We identified unchanged alpha diversity and partially altered beta diversity of the intestinal flora. Another important finding was the increase in Proteobacteria and Enterobacteriales and the decrease in Ruminococcaceae among SLE patients. For metabolites, amino acids and short-chain fatty acids were enriched when long-chain fatty acids were downregulated in SLE faecal samples. KEGG analysis showed the significance of the protein digestion and absorption pathway, and association analysis revealed the key role of 3-phenylpropanoic acid and Sphingomonas. Sphingomonas were reported to be less abundant in healthy periodontal sites of SLE patients than in those of HCs, indicating transmission of oral species to the gut. This study contributes to the understanding of the pathogenesis of SLE disease from the perspective of intestinal microorganisms, explains the pathogenesis of SLE, and serves as a basis for exploring potential treatments for the disease.

Pseudomonas aeruginosa bacteremia among liver transplant recipients.

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.

Methicillin-resistant Staphylococcus aureus bacteremia among liver transplant recipients: epidemiology and associated risk factors for morbidity and mortality.

Bacteremia due to Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), complicates the clinical course of liver transplantation and is associated with high morbidity and mortality. Intravascular catheters had been reported to be the most frequent source of MRSA bacteremia. Among bacteremic liver recipients, 26.3%-100% of S. aureus were MRSA. Previous studies identified pre-transplant and post-transplant acquired S. aureus carriage, greater severity of liver disease, hepatocellular carcinoma and infection with immuno-modulatory viruses as predictors of S. aureus bacteremia in liver recipients. MRSA bacteremia accompanied by pneumonia and abdominal infections was related to mortality. Vancomycin, as well as daptomycin, is a first-line antibiotic for MRSA bacteremia. The purpose of this review is to better understand the characteristics of MRSA bacteremia by summarizing the epidemiology and antimicrobial resistance of S. aureus, the primary source, and related risk factors for morbidity and mortality of MRSA bacteremia. We have also explored the diagnostic, therapeutic and preventive measures for MRSA bacteremia to improve the outcomes of liver recipients.

Epidemiology, susceptibility, and risk factors for acquisition of MDR/XDR Gram-negative bacteria among kidney transplant recipients with urinary tract infections.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Prospective evaluation of the chromogenic medium CandiSelect 4 for differentiation and presumptive identification of non-Candida albicans Candida species.

Rapid identification of pathogenic yeasts is a crucial step in timely and appropriate antifungal therapy. For diagnostics in the clinical laboratory, simplified alternatives to barcoding are needed. CandiSelect 4 (CS4) medium, a chromogenic medium for isolation of clinical yeasts, allows routine recognition of Candida albicans and presumptive identification of Candida tropicalis, Candida glabrata, and Candida krusei. We evaluated an extension of this method with 46 non-Candida albicans Candida (NCAC) and 7 Malassezia species. The medium supported growth of all species tested and a wide diversity of cultural types were observed. Colony colours were in violet, turquoise (including green and blue), or white tinges. Eight NCAC species produced violet pigmentation similar to that of C. albicans. Most NCAC species, including C. glabrata and C. tropicalis were distributed in the turquoise group. Malassezia species were invariably blue.