Antimicrobial activity of ceftobiprole against Gram-negative and Gram-positive pathogens: results from INVITA-A-CEFTO Brazilian study

Ceftobiprole is a broad-spectrum cephalosporin with potent activity against staphylococci, including those resistant to oxacillin, as well as against most Gram-negative bacilli including Pseudomonas aeruginosa. In this study, the in vitro activity of ceftobiprole and comparator agents was tested against bacterial isolates recently collected from Brazilian private hospitals. A total of 336 unique bacterial isolates were collected from hospitalized patients between February 2008 and August 2009. Each hospital was asked to submit 100 single bacterial isolates responsible for causing blood, lower respiratory tract or skin and soft tissue infections. Bacterial identification was confirmed and antimicrobial susceptibility testing was performed using CLSI microdilution method at a central laboratory. The CLSI M100-S21 (2011) was used for interpretation of the antimicrobial susceptibility results. Among the 336 pathogens collected, 255 (75.9%) were Gram-negative bacilli and 81 (24.1%) were Gram-positive cocci. Although ceftobiprole MIC50 values for oxacillin resistant strains were two-fold higher than for methicillin susceptible S. aureus, ceftobiprole inhibited 100% of tested S. aureus at MICs 6 µg/mL for both species. Our results showed that ceftobiprole has potent activity against staphylococci and E. faecalis, which was superior to that of vancomycin. Our data also indicates that ceftobiprole demonstrated potency comparable to that of cefepime and ceftazidime against key Gram-negative species.Janssen-CilagUniversidade Federal de São Paulo (UNIFESP) Post-graduation Course in SciencesUNIFESPUNIFESP, Post-graduation Course in SciencesSciEL

Emerging importance of multidrug-resistant Acinetobacter species and Stenotrophomonas maltophilia as pathogens in seriously ill patients: Geographic patterns, epidemiological features, and trends in the SENTRY Antimicrobial Surveillance Program (1997-1999)

As part of the SENTRY Antimicrobial Surveillance Program, a total of 1078 Acinetobacter species and 842 Stenotrophomonas maltophilia isolates were collected between January 1997 and December 1999 from 5 geographic regions (Canada, the United States, Latin America, Europe, and the Asia-Pacific). the frequency of infections (by geographic region and body site), including those due to imipenem-resistant Acinetobacter species and trimethoprim-sulfamethoxazole (TMP-SMZ)-resistant S. maltophilia, was evaluated. the possibility of seasonal variations in bloodstream infections caused by Acinetobacter species was studied, as was the activity of several therapeutic antimicrobials against all strains. Acinetobacter species and S. maltophilia were most frequently associated with pulmonary infections, independent of the region evaluated. in contrast, patterns of antimicrobial resistance markedly varied among distinct geographic regions, especially for nosocomial isolates. Although the carbapenems were the most active antimicrobials against Acinetobacter species, nearly 11.0% of the nosocomial isolates were resistant to this drug group in both regions. TMP-SMZ, ticarcillin-clavulanic acid, gatifloxacin, and trovafloxacin were the only agents with consistent therapeutic activity against S. maltophilia isolates. Rates of resistance to TMP-SMZ ranged from 2% in Canada and Latin America to 10% in Europe. the geographic differences in resistance patterns among Acinetobacter species and S. maltophilia isolates observed in this study emphasize the importance of local surveillance in determining the most adequate therapy for acinetobacter and S. maltophilia infections and the possible clonal, epidemic nature of occurrence.Universidade Federal de São Paulo, Div Infect Dis, BR-04025010 São Paulo, BrazilUniv Iowa, Coll Med, Iowa City, IA USAQueen Elizabeth II Hlth Sci Ctr, Halifax, NS, CanadaBellvitge Hosp, Barcelona, SpainUniv Utrecht, Utrecht, NetherlandsUniversidade Federal de São Paulo, Div Infect Dis, BR-04025010 São Paulo, BrazilWeb of Scienc

A perspetiva dos professores de educação especial sobre a importância da expressão dramática como técnica psicopedagógica no desenvolvimento da comunicação da criança com perturbação de Asperger

Os princípios pelos quais a escola inclusiva se rege defendem que os alunos não devem apenas estar juntos, mas acima de tudo, devem aprender juntos, de forma a perceberem que a escola é de todos e para todos, ainda que dentro das suas diferenças. Terá o professor capacidades, conhecimentos e estratégias suficientes para abraçar este desafio? Numa tentativa de aprofundarmos o nosso conhecimento acerca da Perturbação de Asperger propomo-nos a desenvolver um trabalho que defina a doença, dentro do já então conhecido, e evidencie tanto as “fragilidades” como as “capacidades” dos portadores, carinhosamente apelidados de “Aspies”. Trata-se de uma tentativa de reunir os conhecimentos necessários para começar a entender a essência dos Asperger. Porque é que na opinião do psicólogo clínico Tony Attwood, especialista mundial nesta Perturbação, precisamos de pessoas com Asperger, sugerindo que estes indivíduos possam ser, de alguma forma, especiais e capazes de grandes feitos. Neste sentido, surge este estudo para tentar perceber a perspetiva dos professores de Educação Especial sobre a importância da Expressão Dramática como técnica psicopedagógica no desenvolvimento da comunicação da criança com Perturbação de Asperger. Pretendemos perceber a influência que a utilização desta técnica pode ter no desenvolvimento comunicacional da criança com Perturbação de Asperger, pois talvez seja relevante sugerir a elaboração de um programa de treino de competências comunicacionais que utilize a Expressão Dramática. A Expressão Dramática vai além do seu papel de ferramenta lúdica e de distração, daí a importância de se conhecer as vantagens da sua utilização nesta área e tentar perceber se pode contribuir ou não para o sucesso de uma criança com esta problemática

Novel beta-Lactams

The beta-lactam class constitutes the largest group of antimicrobial agents, which includes penicillins, cephalosporins, monobactams, and carbapenems. These compounds, which have in common the beta-lactam ring in their structure, are the most prescribed antibiotic class due to their clinical efficacy and safety. This article reviews the beta-lactam compounds which have been recently approved by the United States Food and Drug Administration (US-FDA) or have reached at least phase III of development. We also discuss ME1036, a carbapenem with anti-methicillin-resistant Staphylococcus aureus (MRSA) activity, which is in phase 11 of development. An important advance in the beta-lactam field was the development of cephalosporins and carbapenems with potent anti-MRSA activity such as ceftobiprole, ceflaroline and ME1036. This manuscript also reviews data on doripenem, a new 1-beta-methyl carbapenem that shows potent in vitro activity against Gram-positive and -negative pathogens, and a low propensity to select for in vitro resistance in Pseudomonas aeruginosa and, Enterobacteriaceae. In addition, doripenem showed to be a safe and effective drug in phase III clinical trials that resulted in its recent US-FDA approval. Although ME1036 is still in phase II of development its data was included in this revision since it is one of the first carbapenems to demonstrate anti-MRSA in vitro activity and efficacy in animal models of MRSA infection.Univ Fed Sao Paulo, Div Infect Dis, Dept Med, UNIFESP EPM, Sao Paulo, BrazilJMI Labs, N Liberty, IA USAUniv Fed Sao Paulo, Div Infect Dis, Dept Med, UNIFESP EPM, Sao Paulo, BrazilWeb of Scienc

Evaluation of in vitro activity of new fluoroquinolones, cephalosporins and carbapenems against 569 gram-negative bacteria

OBJECTIVE. Evaluation of the in vitro activity of new fluoroquinolones, cephalosporins and carbapenems against gram-negative bacteria. MATERIAL AND METHOD. A total of 569 clinical isolates were obtained from inpatients at São Paulo Hospital - UNIFESP/EPM in June and July of 1992. The species distribution was as follows: Enterobacter sp. (62), Escherichia coli (308), Klebsiella pneumoniae (27), Klebsiella sp. (9), Proteus mirabilis (23), Pseudomonas aeruginosa (88), Pseudomonas sp. (4), Serratia sp. (30) and other gram-negatives (7). Susceptibility tests were performed by broth microdilution. The antimicrobials agents tested were: ciprofloxacin, ofloxacin, levofloxacin, grepafloxacin, DU 6859-a, ceftazidime, cefepime, FK 037, imipenem, meropenem and biapenem. RESULTS. DU 6859-a showed the highest antimicrobial activity among the fluoroquinolones. It was two- to four-fold more active than ciprofloxacin against some species. The potency and antimicrobial spectrum were similar between the fourth-generation cephalosporins against Enterobacteriaceae, except for Enterobacter sp. strains which were more susceptible to cefepime than they were to cefetazidime or FK 037. When testing Pseudomonas aeruginosa, ceftazidime was slightly more active than the other cephalosporins. Against Enterobacteriaceae and Pseudomonas aeruginosa strains, meropenem was more active than imipenem or biapenem. In addition, the percentage of strains, susceptible to meropenem was higher than the percentage susceptible to the other cerbapenems against these species. CONCLUSION. The new antimicrobial agents demonstrated in vitro activity higher than that of agents commercially avaliable. However, more studies are necessary to further evaluate the in vivo activity and the clinical benefit of these compounds.OBJETIVO. A proposta deste estudo foi a avaliação da atividade in vitro de novos antimicrobianos da classe das fluoroquinolonas, das cefalosporinas e dos carbapenens contra bactérias gram-negativas. MATERIAL E MÉTODO. Foram avaliadas 569 amostras clínicas isoladas no Hospital São Paulo - UNIFESP/EPM, no período compreendido entre junho e julho de 1992. A distribuição das espécies foi: Enterobacter sp. (62), Escherichia coli (308), Klebsiella pneumoniae (27), Klebsiella sp. (9), Proteus mirabilis (23), Pseudomonas aeruginosa (88), Pseudomonas sp. (4), Serratia sp. (30) e outros gram-negativos (7). Os testes de sensibilidade aos antimicrobianos avaliados (ciprofloxacina, ofloxacina, levofloxacina, grepafloxacina, DU 6859-a, ceftazidima, cefepima, FK 037, imipenem, meropenem e biapenem) foram realizados pela técnica de microdiluição em caldo. RESULTADOS. A fluoroquinolona mais potente foi a DU 6859-a; em algumas amostras, apresentou potência duas a quatro vezes superior àquela apresentada pela ciprofloxacina. As novas cefalosporinas de 4ª geração apresentaram potência e espectro de ação semelhantes nas amostras de Enterobacteriaceae, com exceção das amostras de Enterobacter sp., para as quais a cefepima foi mais ativa, e das amostras de P. aeruginosa, para as quais a cefalosporina mais potente e com maior percentagem de suscetibilidade foi a ceftazidima. O meropenem foi o carbapenem mais potente e com maior percentagem de suscetibilidade nas amostras estudadas. CONCLUSÃO. As novas drogas apresentaram, em geral, melhor atividade in vitro do que drogas da mesma classe já utilizadas na prática clínica. Porém, mais estudos serão necessários para avaliar a atividade in vivo desses agentes e sua real utilidade clínica

In vitro susceptibility of Burkholderia cepacia complex isolates: Comparison of disk diffusion, Etest (R), agar dilution, and broth microdilution methods

Broth microdilution, agar dilution, Etest (R) and disk diffusion techniques were compared to evaluate the susceptibility profile of 82 Bcc clinical isolates against six antimicrobials as recommended by CLSI. Broth microdilution was considered the "gold standard" method. The regression analysis was applied to determine the essential (EA) and categorical (CA) agreement rates. STX (MIC50, 1 mg/L) was the most potent antimicrobial tested against Bcc isolates. The worst in vitro activity was observed for chloramphenicol (MIC50, 16 mg/L) and ticarcillin-clavulanic acid (MIC50, >256 mg/L). The EA among broth microdilution and agar dilution results was good for the majority of antimicrobial tested. When comparing broth microdilution and Etest (R), ceftazidime, SXT and chloramphenicol exhibited EA rates below 90%. SXT showed an excellent CA (100%) when dilution methodologies were compared. However, a low CA rate was found for this agent between dilution and disk diffusion methodologies resulting in unacceptable very major and minor error rates. (C) 2016 Elsevier Inc. All rights reserved.Univ Fed Sao Paulo, Escola Paulista Med, Dept Internal Med, Lab Alerta,Div Infect Dis, Sao Paulo, BrazilUniv Estado Rio de Janeiro, Fac Ciencias Med, Dept Microbiol Imunol & Parasitol, Rio De Janeiro, BrazilLaboratório Alerta, Division of Infectious Diseases, Departament of Internal Medicine, Escola Paulista de Medicina/Universidade Federal de São Paulo, São Paulo, BrazilWeb of ScienceFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP: 2012/04,910-

Metallo-β-lactamase-production in meropenem-susceptible Pseudomonas aeruginosa isolates: risk for silent spread

The aim of this study was to characterize two metallo-β-lactamases (MBLs)-producing Pseudomonas aeruginosa clinical isolates showing meropenem susceptibility. Antimicrobial susceptibility was assessed by automated testing and Clinical and Laboratory Standards Institute agar dilution method. MBL production was investigated by phenotypic tests. Molecular typing was determined by pulsed field gel electrophoresis (PFGE). MBL-encoding genes, as well as their genetic context, were identified by polymerase chain reaction (PCR) and sequencing. The location of blaIMP-16 was determined by plasmid electrophoresis, Southern blot and hybridization. Transcriptional levels of blaIMP-16, mexB, mexD, mexF, mexY, ampC and oprD were determined by semi-quantitative real time PCR. The P. aeruginosa isolates studied, Pa30 and Pa43, showed imipenem and meropenem susceptibility by automated testing. Agar dilution assays confirmed meropenem susceptibility whereas both isolates showed low level of imipenem resistance. Pa30 and Pa43 were phenotypically detected as MBL producers. PFGE revealed their clonal relatedness. blaIMP-16 was identified in both isolates, carried as a single cassette in a class 1 integron that was embedded in a plasmid of about 60-Kb. Pa30 and Pa43 overexpressed MexAB-OprM, MexCD-OprJ and MexXY-OprM efflux systems and showed basal transcriptional levels of ampC and oprD. MBL-producing P. aeruginosa that are not resistant to meropenem may represent a risk for therapeutic failure and act as silent reservoirs of MBL-encoding genes

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