To evaluate clinical practices for ESBL-producing urinary tract infection (UTI) in France.
Methods
We performed an observational, retrospective, cross-sectional, hospital-based study in 22 pediatric departments of university or secondary care hospitals. We collected data of the last five patients presenting with ESBL-producing UTI in 2012 and the physicians’ therapeutic approach to two case vignettes of acute non-septic ESBL-producing pyelonephritis (7-month-old girl) and cystitis (30-month-old girl). The adequacy of the therapeutic decision was analyzed by a panel of independent infectious disease experts.
Results
A total of 80 case patients of ESBL-producing UTI were collected: 54 with acute pyelonephritis (mean age: 28 months, female: 66%), of whom 98% received an intravenous ESBL-adapted antibiotic treatment and 55% a two-drug antibiotic therapy. Carbapenems were used in 56% of cases and aminoglycosides in 36%. Of the 26 cystitis patients (mean age: 5 years, female: 73%), 85% were treated with antibiotics, including three intravenously (carbapenems = 2). For the case vignettes, physicians (n = 85) would have treated the pyelonephritis patient with carbapenems (76%) and/or aminoglycosides (68%); 71% would have used a two-drug antibiotic treatment. The cystitis patient would have been treated intravenously by 29% of physicians; 8% would have used a two-drug antibiotic treatment, 16% would have prescribed carbapenems, and 11% aminoglycosides. Antibiotic treatments were deemed appropriate in 37% of cases.
Conclusions
Antimicrobial treatment for ESBL-producing UTI greatly varies, and carbapenems are excessively prescribed. Specific guidelines for ESBL infections are required. 相似文献
Objectives: The first goal of this study was to empirically identify, among university students, groups with varying levels of risk based on indicators of gambling and substance use. The second goal was to compare the identified groups on various demographic characteristics.
Methods: The study comprised of 2139 full-time undergraduate students, representative of university students in Montreal, Canada. A 3-step latent class logistic regression analysis was performed to identify groups and compare them on demographic characteristics.
Results: The statistical fit indices of the latent class analysis revealed a four-class solution. Class 1 (30.1% of the sample) included non-gamblers with low probabilities of substance use. Class 2 (11.2% of the sample) grouped non-gamblers with high-risk patterns of consumption. Class 3 (36.42% of the sample) included gamblers who are low-risk substance users, and individuals in Class 4 (22.25% of the sample) reported risky patterns of gambling and substance-using behaviors. Results of the logistic regression suggested that gender, being born in Canada, and working full- or part-time are significant predictors of class membership. Participants in both groups labeled at-risk (with and without gambling) were also more likely to report psychological distress and to live outside the family environment.
Conclusions: This study raises important questions regarding the choice of preventive models and feeds into the long-standing debate around universal versus high-risk approaches. 相似文献
In mammals, amino acid metabolism has evolved to control immune responses. Autoimmune diseases are heterogeneous conditions that involve the breakdown of tolerogenic circuitries and consequent activation of autoreactive immune cells. Therefore, critical enzymes along amino acid degradative pathways may be hijacked to keep in check autoimmunity. We examined here current knowledge of indoleamine 2,3-dioxygenase 1 (IDO1) and arginase 1 (ARG1), the main enzymes catabolizing tryptophan and arginine, respectively, in organ-specific and systemic autoimmune diseases as well as in the development of autoantibodies to therapeutic proteins. At variance with neoplastic contexts, in which it is known to act as a pure immunosuppressive molecule, ARG1 exhibited a protective or pathogenetic profile, depending on the disease. In contrast, in several autoimmune conditions, the bulk of data indicated that drugs capable of potentiating IDO1 expression and activity may represent valuable therapeutic tools and that IDO1-based immunotherapeutic protocols could be more effective if tailored to the genetic profile of individual patients. 相似文献
Caenorhabditis elegans spermiogenesis involves spermatid activation into spermatozoa. Activation occurs through either SPE‐8 class‐dependent or class‐independent pathways. Pronase (Pron) activates the SPE‐8 class‐dependent pathway, whereas no in vitro tools are available to stimulate the SPE‐8 class‐independent pathway. Thus, whether there is a functional relationship between these two pathways is currently unclear. In this study, we found that proteinase K (ProK) can activate the SPE‐8 class‐independent pathway. In vitro spermiogenesis assays using Pron and ProK suggested that SPE‐8 class proteins act in the hermaphrodite‐ and male‐dependent spermiogenesis pathways and that some spermatid proteins presumably working downstream of spermiogenesis pathways, including MAP kinases, are preferentially involved in the SPE‐8 class‐dependent pathway. We screened a library of chemicals, and a compound that we named DDI‐1 inhibited both Pron‐ and ProK‐induced spermiogenesis. To our surprise, several DDI‐1 analogues that are structurally similar to DDI‐1 blocked Pron, but not ProK, induced spermiogenesis. Although the mechanism by which DDI‐1 blocks spermiogenesis is yet unknown, we have begun to address this issue by selecting two DDI‐1‐resistant mutants. Collectively, our data support a model in which C. elegans male and hermaphrodite spermiogenesis each has its own distinct, parallel pathway. 相似文献
ScopeThe aim of these guidelines is to provide recommendations for decolonizing regimens targeting multidrug-resistant Gram-negative bacteria (MDR-GNB) carriers in all settings.MethodsThese evidence-based guidelines were produced after a systematic review of published studies on decolonization interventions targeting the following MDR-GNB: third-generation cephalosporin-resistant Enterobacteriaceae (3GCephRE), carbapenem-resistant Enterobacteriaceae (CRE), aminoglycoside-resistant Enterobacteriaceae (AGRE), fluoroquinolone-resistant Enterobacteriaceae (FQRE), extremely drug-resistant Pseudomonas aeruginosa (XDRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), cotrimoxazole-resistant Stenotrophomonas maltophilia (CRSM), colistin-resistant Gram-negative organisms (CoRGNB), and pan-drug-resistant Gram-negative organisms (PDRGNB). The recommendations are grouped by MDR-GNB species. Faecal microbiota transplantation has been discussed separately. Four types of outcomes were evaluated for each target MDR-GNB:(a) microbiological outcomes (carriage and eradication rates) at treatment end and at specific post-treatment time-points; (b) clinical outcomes (attributable and all-cause mortality and infection incidence) at the same time-points and length of hospital stay; (c) epidemiological outcomes (acquisition incidence, transmission and outbreaks); and (d) adverse events of decolonization (including resistance development). The level of evidence for and strength of each recommendation were defined according to the GRADE approach. Consensus of a multidisciplinary expert panel was reached through a nominal-group technique for the final list of recommendations.RecommendationsThe panel does not recommend routine decolonization of 3GCephRE and CRE carriers. Evidence is currently insufficient to provide recommendations for or against any intervention in patients colonized with AGRE, CoRGNB, CRAB, CRSM, FQRE, PDRGNB and XDRPA. On the basis of the limited evidence of increased risk of CRE infections in immunocompromised carriers, the panel suggests designing high-quality prospective clinical studies to assess the risk of CRE infections in immunocompromised patients. These trials should include monitoring of development of resistance to decolonizing agents during treatment using stool cultures and antimicrobial susceptibility results according to the EUCAST clinical breakpoints. 相似文献
In contrast to rats, mouse models are nowadays generally used for the investigation of immune responses and immune-mediated diseases, there are many different strains and mouse-specific tools available, and it is easy to generate transgenic and constitutive or inducible knockout mice for any gene. Many immune markers and mechanisms have been detected in mice and have been introduced as gold standard in immunology, however, some turned out to be not unconditionally transferable to the human immune system.Rats have been used more frequently in former days but are mostly outstripped by mice due to the fact that fewer strains are available, they need more space than mice, are more expensive to maintain and breed, and it is extremely difficult to generate transgenic or ko-rats. Consequently, the choice of rat-specific diagnostic tools like antibodies is quite poor and most researchers have switched to mouse models for the investigation of immune mechanisms, while rats are still widely used for toxicology by the pharmaceutical industry. However, it should be taken into consideration that there are some immunological similarities between rats and humans that are not presented in mice. Some of them like MHC class II and Foxp3 expression by activated effector T cells we have detected during our research on the immune response of rat models of experimental autoimmune uveitis. 相似文献
MHC class II regulates B cell activation, proliferation, and differentiation during cognate B cell-T cell interaction. This is, in part, due to the MHC class II signaling in B cells. Activation of MHC Class II in human B cells or “primed” murine B cells leads to tyrosine phosphorylation, calcium mobilization, AKT, ERK, JNK activation. In addition, crosslinking MHC class II with monoclonal Abs kill malignant human B cells. Several humanized anti-HLA-DR/MHC class II monoclonal Abs entered clinical trials for lymphoma/leukemia and MHC class II-expressing melanomas. Mechanistically, MHC class II is associated with a wealth of transmembrane proteins including the B cell-specific signaling proteins CD79a/b, CD19 and a group of four-transmembrane proteins including tetraspanins and the apoptotic protein MPYS/STING. Furthermore, MHC class II signals are compartmentalized in the tetraspanin-enriched microdomains. In this review, we discuss our current understanding of MHC class II signaling in B cells focusing on its physiological significance and the therapeutic potential. 相似文献