Sensibilidade das enterobacteriáceas produtoras de beta-lactamases de espectro alargado à fosfomicina

Introdução: A emergência de enterobacteriáceas produtoras de beta-lactamases de espectro alargado (ESBL) nos últimos anos representa um problema de saúde pública, escasseando alternativas eficazes para o seu tratamento. Vários trabalhos internacionais têm demonstrado uma sensibilidade in vitro muito elevada destas bactérias à fosfomicina, havendo alguns que testaram a eficácia clínica do tratamento de cistites agudas não complicadas no subgrupo das Escherichia coli com resultados promissores. No Hospital Prof. Dr. Fernando Fonseca EPE (HFF) tem havido um aumento anual progressivo do isolamento destes patogéneos. Os autores pretenderam testar a sensibilidade das enterobacteriáceas produtoras de ESBL à fosfomicina no HFF e averiguar o eventual potencial terapêutico. Material e métodos: Estudo prospectivo, durante 6 meses, no qual foi testada a sensibilidade à fosfomicina das enterobacteriáceas produtoras de ESBL isoladas. Foi utilizado o equipamento VITEK 2® para identificação das estirpes. A susceptibilidade à fosfomicina foi determinada através do método de difusão de disco (Oxoid®). O tratamento estatístico foi realizado através do programa Microsoft Excel®. Resultados: Foram identificadas 150 enterobacteriáceas ESBL, das quais 52% corresponderam a Klebsiella pneumoniae e 44% a Escherichia coli. Cerca de 88% das Escherichia coli e 68% das Klebsiella pneumoniae apresentaram sensibilidade à fosfomicina. Conclusões: De acordo com os dados obtidos a nível internacional e no nosso hospital, os autores recomendam a utilização da fosfomicina para tratamento de cistites agudas não complicadas provocadas por Escherichia coli produtoras de ESBL, sugerindo, concomitantemente, a realização de trabalhos futuros de eficácia clínica para consubstanciar esta prática e recomendação.

INTERFERON BETA-1A TREATMENT IN HTLV-1-ASSOCIATED MYELOPATHY/TROPICAL SPASTIC PARAPARESIS: A CASE REPORT

Here a young patient (< 21 years of age) with a history of infective dermatitis is described. The patient was diagnosed with myelopathy associated with HTLV-1/tropical spastic paraparesis and treated with interferon beta-1a. The disease was clinically established as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and laboratory tests confirmed the presence of antibodies to HTLV-1 in the cerebrospinal fluid (CSF). Mumps, cytomegalovirus, Epstein-Barr virus, schistosomiasis, herpes virus 1 and 2, rubella, measles, varicella-zoster toxoplasmosis, hepatitis, HIV, and syphilis were excluded by serology. The patient was diagnosed with neurogenic bladder and presented with nocturia, urinary urgency, paresthesia of the lower left limb, a marked reduction of muscle strength in the lower limbs, and a slight reduction in upper limb strength. During the fourth week of treatment with interferon beta-1a, urinary urgency and paresthesia disappeared and clinical motor skills improved.

Testagem do 1 - beta - D - Ribofuranosil, 1.2.4 - triazole - 3 - carboxamide em pacientes com hepatite

Realizou-se estudo do tipo duplo anonimato em 18 pacientes com hepatite aguda benigna. O gruoo experimental foi testado com uma provável droga de ação antiviral: 1-BETA-D-RIBOFURANOSIL, 1,2,4-TRIAZOLE-3- CARBOXAMIDE. O grupo controle ingeriu um placebo de lactose. Teve-se especial cuidado na seleção de pacientes, incluindo apenas pacientes que preenchessem critérios bem estabelecidos. Os pacientes foram seguidos semanalmente, avaliando-os clínica e laboratorialmente. Os resultados não evidenciaram diferenças significativas entre os dois grupos, sugerindo-se estudos com casuística mais numerosa e em regime de internação hospitalar.

Regulatory Cells, Cytokine Pattern and Clinical Risk Factors for Asthma in Infants and Young Children with Recurrent Wheeze

Several risk factors for asthma have been identified in infants and young children with recurrent wheeze. However, published literature has reported contradictory findings regarding the underlying immunological mechanisms. OBJECTIVES: This study was designed to assess and compare the immunological status during the first 2 years in steroid-naive young children with >or= three episodes of physician-confirmed wheeze (n=50), with and without clinical risk factors for developing subsequent asthma (i.e. parental asthma or a personal history of eczema and/or two of the following: wheezing without colds, a personal history of allergic rhinitis and peripheral blood eosinophilia >4%), with age-matched healthy controls (n=30). METHODS: Peripheral blood CD4(+)CD25(+) and CD4(+)CD25(high) T cells and their cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), GITR and Foxp3 expression were analysed by flow cytometry. Cytokine (IFN-gamma, TGF-beta and IL-10), CTLA-4 and Foxp3 mRNA expression were evaluated (real-time PCR) after peripheral blood mononuclear cell stimulation with phorbol 12-myristate 13-acetate (PMA) (24 h) and house dust mite (HDM) extracts (7th day). RESULTS: Flow cytometry results showed a significant reduction in the absolute number of CD4(+)CD25(high) and the absolute and percentage numbers of CD4(+)CD25(+)CTLA-4(+) in wheezy children compared with healthy controls. Wheezy children at a high risk of developing asthma had a significantly lower absolute number of CD4(+)CD25(+) (P=0.01) and CD4(+)CD25(high) (P=0.04), compared with those at a low risk. After PMA stimulation, CTLA-4 (P=0.03) and Foxp3 (P=0.02) expression was diminished in wheezy children compared with the healthy children. After HDM stimulation, CTLA-4 (P=0.03) and IFN-gamma (P=0.04) expression was diminished in wheezy children compared with healthy children. High-risk children had lower expression of IFN-gamma (P=0.03) compared with low-risk and healthy children and lower expression of CTLA-4 (P=0.01) compared with healthy children. CONCLUSIONS: Although our findings suggest that some immunological parameters are impaired in children with recurrent wheeze, particularly with a high risk for asthma, further studies are needed in order to assess their potential as surrogate predictor factors for asthma in early life.

Avaliação da expressão de interleucina 1 beta (IL-1β) e antagonista do receptor de interleucina 1 (IL-1Ra) em pacientes com hanseníase

A hanseníase é uma doença infectocontagiosa espectral que acompanha-se por uma série de eventos imunológicos desencadeados pela resposta do hospedeiro frente ao agente etiológico, o Mycobacterium leprae. Evidências sugerem que a indução e manutenção da resposta imune/inflamatória na hanseníase estão vinculadas a interações de múltiplas células e fatores solúveis, particularmente através da ação de citocinas. Nesse estudo, foram mensurados níveis de IL-1β e IL-1Ra de 37 casos novos de hanseníase acompanhados ao longo do tratamento e 30 controles sadios pelo teste ELISA. A coleta de sangue periférico foi realizada em quatro tempos para os casos de hanseníase (pré-tratamento com PQT, 2ª dose, 6ª dose e pós-PQT) e em único momento para os controles. Na comparação dos níveis das moléculas de casos no pré-PQT e controles, houve diferença estatisticamente significativa somente para IL-1β. Nossos resultados sugerem a participação dessa citocina no processo imune/inflamatório.

Detecção de metalo-beta-lactamase em Pseudomonas aeruginosa isoladas de pacientes hospitalizados em Goiânia, Estado de Goiás

Pseudomonas aeruginosa é uma bactéria frequentemente isolada no ambiente hospitalar. Este estudo teve como objetivo avaliar o perfil de suscetibilidade de Pseudomonas aeruginosa previamente isoladas de pacientes internados em um hospital de Goiânia (Goiás-Brasil); realizar a triagem fenotípica para a produção de metalo-beta-lactamase e detectar os genes das mesmas pela técnica de "Polimerase Chain Reaction". Foram avaliadas 75 Pseudomonas aeruginosa isoladas no período de janeiro de 2005 a janeiro de 2007. A identificação bioquímica foi realizada pelo sistema API 20E® e o antibiograma pelo método de Kirby-Bauer. Entre os 62 isolados que foram resistentes ao imipenem e à ceftazidima, 35 (56,4%) apresentaram produção de metalo-beta-lactamase e em 26 (74,3%) destes, foi detectado o gene blaSPM-1. A frequência de Pseudomonas aeruginosa produtoras de metalo-beta-lactamase sugere um maior controle da disseminação de resistência no ambiente hospitalar.

Crystallographic studies of proteins involved in the mRNA localization mechanisms in Drosophila melanogaster and amidation of the peptidoglycan residues in Staphylococcus aureus

Part of the work described in this chapter, was the subject of the following publication: D. Vieira, T. a. Figueiredo, A. Verma, R. G. Sobral, A. M. Ludovice, H. de Lencastre, and J. Trincao, “Purification, crystallization and preliminary X-ray diffraction analysis of GatD, a glutamine amidotransferase-like protein from Staphylococcus aureus peptidoglycan,” Acta Crystallogr. Sect. F Struct. Biol. Commun., vol. 70, no. 5, pp. 1–4, Apr. 2014.

Phenotypic and molecular characterization of CTX-M extended-spectrum beta-lactamase-producing Escherichia coli isolates in Shiraz, Iran

AbstractINTRODUCTIONThe aim of this study was to detect the prevalence of the extended-spectrum beta-lactamase (ESBL)-encoding CTX-M gene in Escherichia coliisolates.METHODS:Phenotypic screening of 376 E. coli isolates for ESBL was conducted using disk diffusion. ESBL-producing isolates were tested using PCR and specific primers. The blaCTX-M cluster was identified using the RFLP method, and its genotype was sequenced.RESULTS:From 202 ESBL-producing E. coli , 185 (91.5%) possessed CTX-M genes. CTX-M-1 subtypes were found in 98% of the isolates. The blaCTX-M gene was identical to CTX-M-15.CONCLUSIONS:A high prevalence of CTX-M-1-producing E. coli apparently exists in Shiraz, Iran.

Occurrence and sensitivity profile of extended spectrum beta-lactamase-producing Enterobacteriaceae at a tertiary hospital in Southern Brazil

Abstract: INTRODUCTION: Nosocomial infections are closely associated with antimicrobial drug resistance. One of the most important mechanisms of resistance to β-lactam antibiotics is the production of extended spectrum β-lactamases (ESBLs). The objective of the present study was to evaluate the prevalence and antimicrobial susceptibility profile of ESBL-producing strains and to assess the evolution of antimicrobial drug resistance between 2007 and 2013 at the Hospital São Vicente de Paulo, Passo Fundo, State of Rio Grande do Sul, Brazil. METHODS: We conducted a descriptive, observational, cross-sectional study. Bacterial culture was performed from January to December 2013. The antimicrobial susceptibility profile of these cultures was determined using the disk diffusion method. Phenotypic screening for ESBL production was performed using the disk approximation method. RESULTS : We analyzed a total of 19,112 cultures, 11.5% of which were positive for Enterobacteriaceae. Of these, 30.3% of the isolates were positive for ESBL production, and the most prevalent species was Klebsiella sp. (37.5%). Over 95% of these isolates showed reduced susceptibility to all cephalosporins, aztreonam, and amoxicillin/clavulanic acid. The isolates also showed high sensitivity to the following antimicrobials: amikacin, meropenem, and piperacillin/tazobactam. Overall, the resistance rates among ESBL-producing Enterobacteriaceae decreased from 2007 to 2013. CONCLUSIONS : In our hospital, the increased sensitivity to certain antimicrobial agents seems to be directly related to the implementation of improvements in the methods to prevent and control nosocomial infections in addition to the natural development of other resistance mechanisms.

New Delhi metallo-beta-lactamase-1-producing Acinetobacter spp. infection: report of a survivor

Abstract: New Delhi metallo-beta-lactamase-1 (NDM-1) is a bacterial enzyme that renders the bacteria resistant to a variety of beta-lactam antibiotics. A 20-year-old man was hospitalized several times for surgical treatment and complications caused by a right-sided vestibular schwannoma. Although the patient acquired several multidrug-resistant infections, this study focuses on the NDM-1-producing Acinetobacter spp. infection. As it was resistant to all antimicrobials tested, the medical team developed a 20-day regimen of 750mg/day metronidazole, 2,000,000IU/day polymyxin B, and 100mg/day tigecycline. The treatment was effective, and the patient recovered and was discharged from the hospital.

Rational manipulation of mRNA folding free energy allows rheostat control of pneumolysin production by Streptococcus pneumoniae

Rational manipulation of mRNA folding free energy allows rheostat control of pneumolysin production by Streptococcus pneumoniae

Beta-adrenergic blocking agents in heart failure

Cardiac dysfunction in heart failure is widely recognized as a progressive process, regardless of the clinical signs and symptoms. An increase in cardiac sympathetic drive is one of the earliest neurohormonal responses occurring in patients with heart failure and may be one of the major causes of the progressive remodeling leading to the decline in myocardial function, and responsible for the poor prognosis of patients with heart failure. Therefore, recent data provided by several appropriately designed clinical trials clearly indicate the benefits of beta-adrenoceptor blocking agents, combined with diuretics, ACE inhibitors, and digoxin in chronic heart failure class II to IV due to systolic ventricular dysfunction. The benefits are related to symptoms, functional capacity, remodeling, and improvement in left ventricular function, reduction in cardiovascular hospitalization, a decrease in the overall and sudden cardiac death rate, and are similar in patients with ischemic or nonischemic cardiomyopathy, independent of age, gender, or functional class. In this review we describe the cardiovascular effects of the increase in sympathetic drive, the pharmacological properties of the beta-blockers most evaluated in heart failure therapy (metoprolol, bisoprolol, and carvedilol), the major clinical trials related to these agents in heart failure, the recommendations for their appropriate use in clinical practice, the precautions to be adopted, and how to handle the more common adverse reactions.