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In 2016, an upsurge of neurologic disease associated with infection with multirecombinant enterovirus A71 subgenogroup C1 lineage viruses was reported in France. These viruses emerged in the 2000s; 1 recombinant is widespread. This virus lineage has the potential to be associated with a long-term risk for severe disease among children.
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We determined the crystal structure of an inactive Ser70Gly mutant of CTX-M-9 in complex with the bulky penicillin piperacillin at precovalent and posthydrolytic stages in the catalytic process. The structures obtained at high resolution were compared with the corresponding structures for the small penicillin benzylpenicillin and the bulky cephalosporin cefotaxime. The findings highlight the key role of the configuration of the carbon adjacent to the acylamino group of the side chain of ß-lactams in the precovalent recognition of substrates.
Assuntos
Antibacterianos/química , Proteínas de Escherichia coli/química , Mutação , Piperacilina/química , beta-Lactamases/química , Antibacterianos/metabolismo , Sítios de Ligação , Cristalografia por Raios X , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Modelos Moleculares , Piperacilina/metabolismo , Conformação Proteica , beta-Lactamases/genética , beta-Lactamases/metabolismo , beta-Lactamas/química , beta-Lactamas/metabolismoRESUMO
OBJECTIVES: To describe the efficacy and safety of prolonged cefazolin course for Staphylococcus infection and the emergence of multidrug-resistant bacteria carriage after treatment. METHODS: Monocentric retrospective cohort study of patients hospitalized for blood stream infections (BSI) and osteoarticular infections (OAI) by methicillin susceptible staphylococcal species treated with cefazolin from January 2015 to July 2017. Rectal and nasal swabs were performed at cefazolin initiation and end of treatment to detect respectively methicillin resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) producing bacteria. RESULTS: Fifty-eight patients were included, 41 had a bacteremia including 22 endocarditis and 22 OAI. Mean duration of treatment was 21.5 days at a mean daily dose of 6.5g/d. Fifty-five (94.5%) received combination therapy. Fifty-two (89.7%) of patients achieved bacteriological cure. Four patients were ESBL carriers at inclusion. No additional ESBL or MRSA were detected by end of treatment. CONCLUSION: Cefazolin appears as an effective and safe treatment for BSI or osteoarticular infection and does not appear to select MRSA or ESBL.
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Antibacterianos/administração & dosagem , Cefazolina/administração & dosagem , Farmacorresistência Bacteriana Múltipla , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/tratamento farmacológico , Idoso , Bacteriemia/tratamento farmacológico , Doenças Ósseas Infecciosas/tratamento farmacológico , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Cloxacilina/administração & dosagem , Endocardite Bacteriana/tratamento farmacológico , Feminino , Humanos , Masculino , Meticilina/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pessoa de Meia-Idade , Estudos Retrospectivos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificaçãoRESUMO
Whole-cell fingerprinting by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) in combination with a dedicated bioinformatic software tool (MALDI Biotyper 2.0) was used to identify 152 staphylococcal strains corresponding to 22 staphylococcal species. Spectra of the 152 isolates, previously identified at the species level using a sodA gene-based oligonucleotide array, were analyzed against the main spectra of 3,030 microorganisms. A total of 151 strains out of 152 (99.3%) were correctly identified at the species level; only one strain was identified at the genus level. The MALDI-TOF MS method revealed different clonal lineages of Staphylococcus epidermidis that were of either human or environmental origin, which suggests that the MALDI-TOF MS method could be useful in the profiling of staphylococcal strains. The topology of the dendrogram generated by the MALDI Biotyper 2.0 software from the spectra of 120 Staphylococcus reference strains (representing 36 species) was in general agreement with that inferred from the 16S rRNA gene-based analysis. Our findings indicate that the MALDI-TOF MS technology, associated with a broad-spectrum reference database, is an effective tool for the swift and reliable identification of Staphylococci.
Assuntos
Técnicas Bacteriológicas/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Staphylococcus/química , Staphylococcus/classificação , Análise por Conglomerados , Humanos , SoftwareRESUMO
Introduction. Infection of cardiac implantable electronic devices is a severe condition associated with high mortality, particularly in patients who are dependent upon heart-pacing devices. Staphylococci are found in 70 % of reported cases. Case presentation. We report the case of a cardiac-pacemaker infection in a 79-year-old man, cumulating a history of rheumatoid arthritis treated by corticosteroids and methotrexate by a recently identified micro-organism: Raoultella planticola. He presented local signs of infection on his VVI pacemaker implantation site and underwent urgent pocket device replacement under cefamandole antibioprophylaxis. On incision thick pus oozed out. It was necessary to perform a complete hardware extraction comprising the pulse generator and the ancient lead. Pus was inoculated into aerobic and anaerobic culture vials and Gram staining unveiled Gram-negative rods. Microbiology analysis identified the organism as R. planticola. A new pacing device was inserted on the contrlateral pectoral region. Ciprofloxacin enabled full recovery. A literature review concerning this pathogen revealed that it is involved in severe infections such as bloodstream infections, peritonitis, cellulitis, pneumonia and lung abscesses, and urinary tract infections. In these case reports, underlying co-morbidities were identified such as solid active neoplasia, recent chemotherapy, corticosteroids, solid-organ-recipient patients and recent open surgery. Conclusion.R. planticola is a serious emerging pathogen and contributes to the burden of various infectious conditions. Its pathogenicity and occurrence should be known by clinicians and a high level of awareness is necessary to precisely identify it provide the correct antibiotic regimen.
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beta-Lactamase-mediated resistance to beta-lactam antibiotics poses a major threat to our antibiotic armamentarium. Among beta-lactamases, a significant threat comes from enzymes that hydrolyze extended-spectrum cephalosporins such as cefotaxime. Among the enzymes that exhibit this phenotype, the CTX-M family is found worldwide. These enzymes have a small active site, which makes it difficult to explain how they hydrolyze the bulky extended-spectrum cephalosporins into the binding site. We investigated noncovalent substrate recognition and product release in CTX-M enzymes using steered molecular dynamics simulation and X-ray diffraction. An arginine residue located far from the binding site favors the capture and tracking of substrates during entrance into the catalytic pocket. We show that the accommodation of extended-spectrum cephalosporins by CTX-M enzymes induced subtle changes in the active site and established a high density of electrostatic interactions. Interestingly, the product of the catalytic reaction initiates its own release because of steric hindrances and electrostatic repulsions. This suggests that there exists a general mechanism for product release for all members of the beta-lactamase family and probably for most carboxypeptidases.