Exploring how structural changes to new Licarin A derivatives effects their bioactive properties against rapid growing mycobacteria and biofilm formation.

Several species of rapidly growing mycobacteria (RGM) have been associated with biofilms in areas such as biomedical devices, water distribution systems, cosmetic surgery, and catheter-related blood infections. Biofilms which exhibit antimicrobial resistance such as those formed by the genus Mycobacterium pose a significant risk to health and are of particular interest to researchers. Licarin A (a neolignan found in numerous plant species e.g. nutmeg) has been reported to show a wide range of biological actions including anti-inflammatory, antioxidant, and antibacterial properties. The aim of this study was to prepare a set of Licarin A derivatives and investigate the impact of specific structural changes on its antimycobacterial ability, and its effect on the biofilm formation of RGM species. Initially, the phenolic sub-unit and alkenyl side chain of Licarin A were modified to create derivatives with a higher partition coefficient; as the activity of a compound against mycobacteria seems to be strongly influenced by its hydrophobicity. Further, polar groups were inserted into the side chain to change the hydrophilic-lipophilic profile of the molecules. Results showed variability in the susceptibility profile of mycobacteria against the Licarin A derivatives under analysis. A number of the derivatives showed significant inhibitory activity of planktonic growth of the three strains of mycobacteria used, with even lower MIC values than those observed with reference drugs and Licarin A itself. Cytotoxicity assays showed they also have low toxicity, confirming that structural modifications to the Licarin A have made improvements to its antimycobacterial properties.

Detection and analysis of different interactions between resistance mechanisms and carbapenems in clinical isolates of Klebsiella pneumoniae

Carbapenems are considered last-line agents for the treatment of serious infections caused by Klebsiella pneumoniae, and this microorganism may exhibit resistance to -lactam antibiotics due to different mechanisms of resistance. We evaluated 27 isolates of K. pneumoniae resistant to carbapenems recovered from inpatients at the University Hospital of Santa Maria-RS from July 2013 to August 2014. We carried out antimicrobial susceptibility, carbapenemase detection, testing for the presence of efflux pump by broth microdilution and loss of porin by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Genetic similarity was evaluated by ERIC-PCR. High levels of resistance were verified by the minimum inhibitory concentration for the antimicrobials tested. The blaKPC gene was present in 89% of the clinical isolates. Blue-Carba and combined disk with AFB tests showed 100% concordance, while the combined disk test with EDTA showed a high number of false-positives (48%) compared with the gold-standard genotypic test. Four isolates showed a phenotypic resistance profile consistent with the overexpression of the efflux pump, and all clinical isolates had lost one or both porins. The ERIC-PCR dendrogram demonstrated the presence of nine clusters. The main mechanism of resistance to carbapenems found in the assessed isolates was the presence of the blaKPC gene.(AU)

Detection and analysis of different interactions between resistance mechanisms and carbapenems in clinical isolates of Klebsiella pneumoniae

Abstract Carbapenems are considered last-line agents for the treatment of serious infections caused by Klebsiella pneumoniae, and this microorganism may exhibit resistance to β-lactam antibiotics due to different mechanisms of resistance. We evaluated 27 isolates of K. pneumoniae resistant to carbapenems recovered from inpatients at the University Hospital of Santa Maria-RS from July 2013 to August 2014. We carried out antimicrobial susceptibility, carbapenemase detection, testing for the presence of efflux pump by broth microdilution and loss of porin by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Genetic similarity was evaluated by ERIC-PCR. High levels of resistance were verified by the minimum inhibitory concentration for the antimicrobials tested. The blaKPC gene was present in 89% of the clinical isolates. Blue-Carba and combined disk with AFB tests showed 100% concordance, while the combined disk test with EDTA showed a high number of false-positives (48%) compared with the gold-standard genotypic test. Four isolates showed a phenotypic resistance profile consistent with the overexpression of the efflux pump, and all clinical isolates had lost one or both porins. The ERIC-PCR dendrogram demonstrated the presence of nine clusters. The main mechanism of resistance to carbapenems found in the assessed isolates was the presence of the blaKPC gene.

Detection and analysis of different interactions between resistance mechanisms and carbapenems in clinical isolates of Klebsiella pneumoniae.

Carbapenems are considered last-line agents for the treatment of serious infections caused by Klebsiella pneumoniae, and this microorganism may exhibit resistance to ß-lactam antibiotics due to different mechanisms of resistance. We evaluated 27 isolates of K. pneumoniae resistant to carbapenems recovered from inpatients at the University Hospital of Santa Maria-RS from July 2013 to August 2014. We carried out antimicrobial susceptibility, carbapenemase detection, testing for the presence of efflux pump by broth microdilution and loss of porin by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Genetic similarity was evaluated by ERIC-PCR. High levels of resistance were verified by the minimum inhibitory concentration for the antimicrobials tested. The blaKPC gene was present in 89% of the clinical isolates. Blue-Carba and combined disk with AFB tests showed 100% concordance, while the combined disk test with EDTA showed a high number of false-positives (48%) compared with the gold-standard genotypic test. Four isolates showed a phenotypic resistance profile consistent with the overexpression of the efflux pump, and all clinical isolates had lost one or both porins. The ERIC-PCR dendrogram demonstrated the presence of nine clusters. The main mechanism of resistance to carbapenems found in the assessed isolates was the presence of the blaKPC gene.

In vitro antimicrobial efficacy of a fixed-dose combination of RHZE against M. tuberculosis

ABSTRACT The use of drugs in fixed-dose combination (FDC) is now recommended by the World Health Organization (WHO) due to the emergence of multidrug-resistant strains of Mycobacterium tuberculosis. FDC uses different drugs against tuberculosis (TB) in a single tablet for phase-intensive therapeutic intervention. This therapy aims to optimize treatment, to prevent inappropriate use of drugs, and to prevent the emergence of new resistant strains. This study aims to evaluate the susceptibility of clinical isolates of M. tuberculosis against rifampicin, isoniazid, ethambutol, and pyrazinamide. The antimicrobials were tested separately and in associations according to FDC. This was used for broth microdilution method, which was compared to the proportions method previously considered as the gold standard. In antimicrobials testing alone, several strains were resistant to one, two, or three drugs. However, when applied to association of drugs in FDC, there was no antimicrobial resistance. The results strengthen the FDC's concept, which aims to unite the four anti-TB drugs to combat bacterial resistance.

Antibiofilm effect of antimicrobials used in the therapy of mycobacteriosis.

Rapidly growing mycobacteria (RGM) are opportunistic pathogens found in the environment. When in biofilms, mycobacteria is highly resistant to antibacterial treatments. The purpose of this study is to evaluate the antibiofilm activity of antimicrobials commonly used in therapy against mycobacteria. The antimicrobial susceptibility of Mycobacterium abscessus, Mycobacterium fortuitum and Mycobacterium massiliense was determined in planktonic and sessile populations. The antimicrobials amikacin, ciprofloxacin, clarithromycin, doxycycline, imipenem and sulfamethoxazole were tested. For each drug, it was evaluated the susceptibility of the pathogen, the ability to inhibit biofilm formation and the resistance of biofilms to antimicrobial activity. Results showed although, the antimicrobials tested are used as an alternative therapy for RGM, M. abscessus proved to be resistant to clarithromycin, beside that, M. massiliense showed a resistant profile to clarithromycin and sulfamethoxazole. Moreover, the inhibition of biofilm formation and its destruction have not been fully met. Considering that the biofilms are a known form of bacterial resistance, the failure of alternatives to inhibit or destroy biofilms can trigger the recurrence of infections. In RGM, besides causing treatment failures, biofilms are a factor of pathogenic risk, since these microorganisms are found in environmental sources and can cause infections easily.

Incidência de meningite por Haemophilus influenzae no RS 1999-2010: impacto da cobertura vacinal / Incidence of meningitis caused by Haemophilus influenzae in the state of Rio Grande do Sul 1999-2010: impact of vaccination campaign

O objetivo deste artigo é analisar e verificar a situação epidemiológica das meningites causadas pelo agente Haemophilus influenzae tipo b nos últimos 10 anos no Rio Grande do Sul. Estudo retrospectivo, descritivo, utilizando o sistema de dados de notificação de meningites, e cobertura vacinal, armazenados em base on line Tabnet - Tabulação de dados Epidemiológicos - CEVS/SES/RS, abrangendo o período de 1999 a 2010. Foram utilizados casos notificados e confirmados, tendo como critério de seleção o ano de inicio dos sintomas, idade, diagnostico e evolução. Foi analisado o Estado do Rio Grande do Sul, representado por 19 coordenadorias de saúde. Comparações entre proporções foram avaliadas pelo teste de z. No RS foram notificados 3043 casos confirmados de meningite bacteriana, sendo 6,77% dos casos causados por H. influenzae. O coeficiente de incidência da meningite por H. influenzae, sem considerar faixa etária, caiu significativamente (95,6%) após 1999, assim como a mortalidade. Crianças menores de um ano continuam sendo as mais acometidas (52%), não havendo alteração na letalidade. Os resultados apresentados revelaram um impacto positivo das estratégias de vacinação contra Hib no Estado do Rio Grande do Sul nos últimos dez anos.

This article seeks to analyze and update the epidemiological situation of meningitis caused by Haemophilus influenzae type b in the past 10 years in the state of Rio Grande do Sul (RS). It is a retrospective, descriptive study, which used the data notification system of meningitis and vaccination campaign coverage, stored in the Epidemiological TABNET online database, for the period from 1999 to 2010. Cases notified and confirmed were used and the selection criteria were the year when the symptoms were detected, age, diagnosis, and evolution. Nineteen health centers in the state of Rio Grande do Sul were analyzed. The z-test was used to evaluate comparisons between the proportions. In the period studied, 3043 confirmed cases of bacterial meningitis were reported, of which 6.77% were caused by H. influenzae. The incidence and mortality rates of meningitis caused by H. influenzae, without taking age group into consideration, fell significantly (95.6%) after 1999. Children under one year old continue to be the most affected (52%), there being no change in lethality. The results presented revealed a positive impact of Hib vaccination strategies in the state of Rio Grande do Sul over the past ten years.

Identification of mycobacteria isolated at University Hospital of Santa Maria, Rio Grande do Sul, Brazil / Identificação de micobactérias isoladas no Hospital Universitário de Santa Maria, Rio Grande do Sul, Brasil

This study evaluated the prevalence of nontuberculous mycobacterium (NTM) in relation to the total number of cases of mycobacterial infections detected in patients admitted at the University Hospital of Santa Maria from 2008 to 2010. From the positive samples for the genus Mycobacterium, 67% belonged to the Mycobacterium tuberculosis complex (MTBC) and 33% of them were classified as NTM. This investigation aims to contribute to the epidemiology of mycobacterioses, inasmuch as patients infected by NTM require distinctive treatment and monitoring in comparison with those infected by MTBC.

Foi avaliada a prevalência de micobactérias não tuberculosas (MNT) em relação ao total de casos de micobacterioses identificadas em pacientes do Hospital Universitário de Santa Maria, entre os anos de 2008 e 2010. Entre as amostras positivas para o gênero Mycobacterium, 67% eram do complexo Mycobacterium tuberculosis (CMTB) e 33% foram classificadas como MNT. Este estudo procura contribuir com a epidemiologia das micobacterioses, uma vez que os pacientes infectados por MNT necessitam de tratamento e acompanhamento diferenciado dos infectados pelo CMTB.

Fatores epidemiológicos do dengue na região central do estado do Rio Grande do Sul, Brasil, 2007 - 2010 / Epidemiological features of dengue in the central region of Rio Grande do Sul state, Brazil, from 2007 to 2010

O objetivo deste estudo foi avaliar fatores epidemiológicos do dengue, nos municípios da 4ª Coordenadoria Regional de Saúde/RS (4a CRS/RS), nos anos de 2007 a 2010. Trata-se de um estudo descritivo, empregando como variáveis: município de notificação; ano de notificação; sexo e faixa etária do paciente; índice de infestação predial (IIP) e índice de Breteau (IB). Foram constatados 13 casos importados da doença, em cinco municípios, sendo a maior ocorrência em Santa Maria. Houve notificação de casos em ambos os sexos e em diferentes faixas etárias. Focos positivos do Aedes aegypti foram encontrados em armadilhas instaladas em pontos estratégicos de Santa Maria e Santiago. O IIP e IB, em ambos os municípios, não representaram risco à saúde pública. Conclui-se, portanto, que as ações de vigilância em saúde devem ser fomentadas com o objetivo de orientar as práticas de controle do vetor, bem como promover a educação sanitária e ambiental, a fim de impedir a instalação de casos autóctones nos municípios estudados.

The aim of this study was to evaluate the epidemiological issues of dengue in the counties of the 4th Coordenadoria Regional de Saúde (government agency to surveillance on public health) of Rio Grande do Sul state, Brazil, during 2007 to 2010. This is a descriptive study, using as variables: cities where dengue was reported; year; sex and age of the patient; infestation (IIP) and Breteau (BI) index. A total of 13 imported cases of the dengue was reported in five cities and higher occurrence was in Santa Maria city. There were notifications of dengue in both sex and in different age groups. Positive foci of Aedes aegypti were found in the traps at strategic points in both cities, Santa Maria and Santiago. BII and BI varied during the studied period in both cities, and, so far, they did not constitute a risk to public health. We conclude that the health surveillance should be enhanced with the purpose of guiding vector control practices, as well as promote health and environmental education in order to prevent the installation of autochthonous dengue cases in the cities studied.

Qualidade higiênico-sanitária dos restaurantes cadastrados na Vigilância Sanitária de Santa Maria, RS, Brasil, no período de 2006 a 2010 / Hygienic-sanitary status of restaurants recorded in the health surveillance unit of Santa Maria, Rio Grande do Sul, Brazil, from 2006 to 2010

O presente estudo teve por objetivo avaliar, através dos roteiros de inspeção, as condições higiênico-sanitárias dos restaurantes cadastrados pela Vigilância Sanitária (VISA) do município de Santa Maria - RS. Neste estudo, foram incluídos 315 roteiros de vistorias provenientes de 120 restaurantes com alvarás sanitários e fiscalizados no período de janeiro de 2006 a dezembro de 2010. As variáveis (a) condições de armazenamento dos alimentos, (b) equipamentos de conservação a frio e a quente, (c) estrutura física do estabelecimento e (d) condições higiênico-sanitária dos manipuladores dos alimentos foram compiladas e avaliadas. Os resultados foram analisados estatisticamente pelo programa SAS (Statistical Analysis System) versão 9.2 e submetidos aos testes de Qui-quadrado e Fischer. Constatou-se que, no ano de 2009, ocorreram os maiores índices de desconformidades legais nos aspectos higênico-sanitários nos estabelecimentos pesquisados. Esse fato pode estar relacionado ao aumento do número de fiscais sanitários contratados, à descentralização do setor de fiscalização, o que possibilitou a realização de um maior detalhamento dos requisitos fundamentais a serem avaliados nos roteiros de vistoria e, consequentemente, havendo um aumento nas notificações oficiais. Além disso, no ano de 2010, os estabelecimentos apresentaram melhores índices de adequação às boas práticas de produção de alimentos. Com base nas informações obtidas, verificou-se que os serviços prestados pelo setor de alimentos da VISA de Santa Maria estão em crescente evolução.

The present study was to evaluate, through the forms of inspection, the sanitary conditions of restaurants registered for Sanitary Surveillance (VISA) in the municipality of Santa Maria, RS, Brazil. This study included 315 inspection forms, from 120 restaurants with sanitary permits from January 2006 to December 2010. The following variables: (a) food storage conditions, (b) equipment for hot and cold storage, (c) the physical structure of establishment and (d) hygienic and sanitary conditions of food handlers, were compiled and evaluated. The results were statistically analyzed by SAS (Statistical Analysis System) version 9.2 and submitted to the chi-square and Fischer tests. It was observed that in 2009 there were higher rates of nonconformities in the legal hygienic and sanitary aspects in the establishments studied. Such fact can be related to the increasing of the number of health inspectors hired, decentralization of surveillance division, what allowed the achievement of a more detailed inspection forms, and consequently there is an increase in official reports. Additionally, in 2010, food establishments had better rates of conformity with food good manufacturing practices. Based on the information obtained, it was found that the services provided by the VISA of Santa Maria, RS, Brazil are in increasing development.

Emprego do bacteriófago D29 na determinação quantitativa da resistência de Mycobacterium tuberculosis à rifampicina e sua correlação com o gene rpo BETA / D29 phage use on Mycobacterium tuberculosis quantitative resistance determination to rifampin and its rpo

O Mycobacterium tuberculosis agente causador da tuberculose tem sido enfoque no cenário mundial, devido à surgimento de cepas resistentes a drogas da primeira linha de tratamento (rifampicina, isoniazida, pirazinamida e etambutol). Em 1998 foram notificadas 82.931 casos de tuberculose, e destes 22 porcento referentes ao Estado de São Paulo. A taxa de resistência a rifampicina no Brasil foi de 1,3 porcento no período de 1994 a 1997. O teste de sensibilidade é recomendado a todas as cepas isoladas com intuito de diagnosticar rapidamente cepas resistentes. Neste trabalho foi apresentada uma nova metodologia para determinação da Concentração Inibitória Mínima (CIM) de rifampicina em cepas de M. tuberculosis utilizando o bacteriófago D29...