Predominance of CTX-M–type extended-spectrum β-lactamase genes among enterobacterial isolates from outpatients in Brazil

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Characterization of CTX-M ESBLs in Enterobacter cloacae, Escherichia coli and Klebsiella pneumoniae clinical isolates from Cairo, Egypt

<p>Abstract</p> <p>Background</p> <p>A high rate of resistance to 3^rdgeneration cephalosporins among Enterobacteriaceae isolates from Egypt has been previously reported. This study aims to characterize the resistance mechanism (s) to extended spectrum cephalosporins among resistant clinical isolates at a medical institute in Cairo, Egypt.</p> <p>Methods</p> <p>Nonconsecutive <it>Klebsiella pneumoniae </it>(Kp), <it>Enterobacter cloacae </it>(ENT) and <it>Escherichia coli </it>(EC) isolates were obtained from the clinical laboratory at the medical institute. Antibiotic susceptibility was tested by CLSI disk diffusion and ESBL confirmatory tests. MICs were determined using broth microdilution. Isoelectric focusing (IEF) was used to determine the pI values, inhibitor profiles, and cefotaxime (CTX) hydrolysis by the β-lactamases. PCR and sequencing were performed using <it>bla</it>_CTX-Mand IS<it>Ecp1</it>-specific primers, with DNA obtained from the clinical isolates. Conjugation experiments were done to determine the mobility of <it>bla</it>_CTX-M.</p> <p>Results</p> <p>All five clinical isolates were resistant to CTX, and were positive for ESBL screening. IEF revealed multiple β-lactamases produced by each isolate, including a β-lactamase with a pI of 8.0 in Kp and ENT and a β-lactamase with a pI of 9.0 in EC. Both β-lactamases were inhibited by clavulanic acid and hydrolyzed CTX. PCR and sequence analysis identified <it>bla</it>_CTX-M-14in Kp and ENT and a <it>bla</it>_CTX-M-15in EC. Both <it>bla</it>_CTX-M-14and <it>bla</it>_CTX-M-15were preceded by IS<it>Ecp1 </it>elements as revealed by partial sequence analysis of the upstream region of the <it>bla</it>_CTX-Mgenes. <it>bla</it>_CTX-M-15 was transferable but not <it>bla</it>_CTX-M-14.</p> <p>Conclusion</p> <p>This is the first report of CTX-M-14 in Kp and ENT isolates from Egypt, the Middle East and North Africa.</p

How to detect carbapenemase producers? A literature review of phenotypic and molecular methods

© 2014 Elsevier B.V. This review describes the current state-of-art of carbapenemase detection methods. Identification of carbapenemases is first based on conventional phenotypic tests including antimicrobial susceptibility testing, modified-Hodge test and carbapenemase-inhibitor culture tests. Second, molecular characterization of carbapenemase genes by PCR sequencing is essential. Third, innovative biochemical and spectrometric detection may be applied

Non-Hodgkin Lymphoma in Children and Adolescents: Progress Through Effective Collaboration, Current Knowledge, and Challenges Ahead

Non-Hodgkin lymphoma is the fourth most common malignancy in children, has an even higher incidence in adolescents, and is primarily represented by only a few histologic subtypes. Dramatic progress has been achieved, with survival rates exceeding 80%, in large part because of a better understanding of the biology of the different subtypes and national and international collaborations. Most patients with Burkitt lymphoma and diffuse large B-cell lymphoma are cured with short intensive pulse chemotherapy containing cyclophosphamide, cytarabine, and high-dose methotrexate. The benefit of the addition of rituximab has not been established except in the case of primary mediastinal B-cell lymphoma. Lymphoblastic lymphoma is treated with intensive, semi-continuous, longer leukemia-derived protocols. Relapses in B-cell and lymphoblastic lymphomas are rare and infrequently curable, even with intensive approaches. Event-free survival rates of approximately 75% have been achieved in anaplastic large-cell lymphomas with various regimens that generally include a short intensive B-like regimen. Immunity seems to play an important role in prognosis and needs further exploration to determine its therapeutic application. ALK inhibitor therapeutic approaches are currently under investigation. For all pediatric lymphomas, the intensity of induction/consolidation therapy correlates with acute toxicities, but because of low cumulative doses of anthracyclines and alkylating agents, minimal or no long-term toxicity is expected. Challenges that remain include defining the value of prognostic factors, such as early response on positron emission tomography/computed tomography and minimal disseminated and residual disease, using new biologic technologies to improve risk stratification, and developing innovative therapies, both in the first-line setting and for relapse

Kinetic characterization of GES-22 beta-lactamase harboring the M169L clinical mutation

The class A p-lactamase GES-22 has been identified in Acinetobacter baumannii isolates in Turkey, and subsequently shown to differ from GES-11 by a single substitution (M169L). Because M169 is part of the omega loop, a structure that is known to have major effects on substrate selectivity in class A beta-lactamases, we expressed, purified and kinetically characterized this novel variant. Our results show that compared with GES-11(6xHis), GES-22(6xHis) displays more efficient hydrolysis of penicillins, and aztreonam, but a loss of efficiency against ceftazidime. In addition, the M169L substitution confers on GES-22 more efficient hydrolysis of the mechanistic inhibitors clavulanic acid and sulbactam. These effects are highly similar to other mutations at the homologous position in other class A beta-lactamases, suggesting that this methionine has a key structural role in aligning active site residues and in substrate selectivity across the class.Recep Tayyip Erdogan University:BAP-2013.102.03.12 Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK): TUBITAK-113Z054 United States Department of Health & Human Services National Institutes of Health (NIH) - USA 1R15AI082416 Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) 2214-

The Shift from Local to Global Visual Processing in 6-Year-Old Children Is Associated with Grey Matter Loss

International audienceBackground: A real-world visual scene consists of local elements (e.g. trees) that are arranged coherently into a global configuration (e.g. a forest). Children show psychological evolution from a preference for local visual information to an adult-like preference for global visual information, with the transition in visual preference occurring around 6 years of age. The brain regions involved in this shift in visual preference have not been described. Methods and Results: We used voxel-based morphometry (VBM) to study children during this developmental window to investigate changes in gray matter that underlie the shift from a bias for local to global visual information. Six-year-old children were assigned to groups according to their judgment on a global/local task. The first group included children who still presented with local visual processing biases, and the second group included children who showed global visual processing biases. VBM results indicated that compared to children with local visual processing biases, children with global visual processing biases had a loss of gray matter in the right occipital and parietal visuospatial areas. Conclusions: These anatomical findings are in agreement with previous findings in children with neurodevelopmental disorders and represent the first structural identification of brain regions that allow healthy children to develop a global perception of the visual world