Bioactive properties of Persea lingue Ness (Lauraceae) fruit and leaf extracts / Propriedades bioativas de extratos de folhas e frutos de Persea lingue Ness (Lauraceae)

Abstract Persea lingue Ness is a tree species that lives mainly in temperate forests of south-central Chile. Its leaves are used in ethnomedicine, the fruit is a drupe similar to that of the avocado and has not been studied. The aim of this study was to determine the cytotoxicity in leukemia cell and antibacterial activity, along with some chemical content characteristics of P. lingue fruit and leaf extracts. The antibacterial activity was determined by the inhibition of bacterial growth in liquid medium assay against Gram-positive and Gram-negative bacteria. The leukemia cell lines Kasumi-1 and Jurkat were used to evaluate the cytotoxic activity by using propidium iodide and AlamarBlue assays. Total phenolic, flavonoid, condensed tannin, alkaloid and lipid contents were evaluated in the fruit and in the leaf extracts. The antioxidant activity of both extracts were also elavaluated. Leaf extract presented the highest content of total phenols, condensed tannins and flavonoids, and also the highest antioxidant activity. While the fruit extract has a higher amount of lipids and alkaloids and the high antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium and Micrococcus luteus. The leaf extract only showed activity against M. luteus. Concerning the cytotoxic activity, only the fruit extract showed cytotoxicity against the cell lines Jurkat and Kasumi-1. P. lingue fruit extract is a potential source of biologically active molecules for the development of new drugs to be used in some types of leukemia, as well as antibacterial agent.

Resumo Persea lingue Ness é uma árvore que vive principalmente na floresta temperada do centro-sul do Chile. As folhas são usadas na etnomedicina. O fruto é uma drupa similar ao abacate e que nunca foi pesquisada anteriormente. O objetivo deste estudo foi o de avaliar a citotoxicidade em células leucêmicas e as atividades antibacterianas, assim como algumas características químicas do extrato de fruto e da folha do P. lingue. As atividades antibacterianas foram determinadas pelo método da inibição do crescimento bacteriano em meio líquido empregando-se bactérias Gram-positivas e Gram-negativas. As linhagens celulares leucêmicas, Kasumi-1 e Jurkat foram usadas para avaliar a atividade citotóxica em ensaios empregando-se iodeto de propídio e AlamarBlue. Foram avaliados os teores totais de fenóis, flavonóides, taninos condensados, alcalóides e lipídeos presentes nos extratos das folhas e dos frutos. As atividades antioxidantes de ambos os extratos também foram avaliadas. O extrato das folhas foi o que apresentou o maior conteúdo de fenóis, taninos condensados e flavonóides totais e a maior atividade antioxidante. Já o extrato de fruto apresentou a maior quantidade de lipídios e alcaloides e a melhor atividade antibacteriana contra Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium e Micrococcus luteus. Já o extrato das folhas apresentou apenas atividade contra M. luteus. Em relação à atividade citotóxica, apenas o extrato do fruto apresentou citotoxicidade contra as linhagens celulares Jurkat e Kasumi-1. Em resumo, o extrato do fruto de P. lingue é uma potencial fonte de moléculas com atividade biológica para o desenvolvimento de novos fármacos a serem utilizados em alguns tipos de leucemia, bem como agente antibacteriano.

Chemical characterization, cytotoxicity, antimicrobial and antioxidant potential of Justicia pectoralis Jacq and Croton jacobinensis Baill extracts

Abstract In this research, aqueous and ethanolic extracts from Justicia pectoralis Jacq and Croton Jacobinensis Baill were characterized. The UPLC-QTOF-MSE analysis was performed on the extracts identified, predominantly, flavonoids, tannins and acids. The extracts did not indicate toxicity in human epithelial cells. C. jacobinensis presented a concentration of phenolics 60.5% higher than J. pectoralis in all scenarios evaluated and, for both samples, the hydroalcoholic extract at 70% exhibited the best efficiency in the extraction (14501.3 and 32521.5 mg GAE 100 g-1 for J. pectoralis and C. jacobinensis, respectively). The antioxidant activity presented a positive correlation with the concentration of phenolics, being 1.186,1 and 1.507,9 µM of Trolox for J. pectoralis and C. jacobinensis at 70% of ethanol; however, it was not verified statistical difference between the ethanolic solutions (p < 0.05). The antimicrobial activity of J. pectoralis extracts was highlighted once was the most effective against gram-positive bacteria. The results suggest that both J. pectoralis and C. jacobinensis extracts present the potential to be applied as natural additives due to their antioxidant and antimicrobial activity and safety. Thus, it is suggesting the development of studies that could investigate the interaction of these plant extracts with food matrices is required

Meningite bacteriana: uma revisão / Bacterial meningitis: a review

A meningite bacteriana é uma inflamação das leptomeninges que envolvem o Sistema Nervoso Central. Essa patologia, que possui diversos agentes etiológicos, apresenta-se na forma de síndrome, com quadro clínico grave. Entre as principais bactérias que causam a meningite, estão a Neisseria meningitis e Streptococcus pneumoniae. A transmissão ocorre através das vias aéreas por meio de gotículas, sendo a corrente sanguínea a principal rota para as bactérias chegarem à barreira hematoencefálica e, a partir dessa, até as meninges. Atualmente existem vários métodos de diagnóstico precisos, onde a cultura de líquido cefalorraquidiano (LCR) é o método padrão ouro. Ademais, a melhora na qualidade do tratamento com beta-lactâmicos e a maior possibilidade de prevenção, devido à elevação do número e da eficácia de vacinas, vem contribuindo para redução dos casos da doença e de sua gravidade. Porém, apesar desses avanços, ainda há um elevado número de mortalidades e sequelas causadas por essa síndrome.

Bacterial meningitis is an inflammation of the leptomeninges that surround the Central Nervous System. This pathology, which has several etiological agents, is presented as a syndrome with a severe clinical scenario. The main bacteria causing meningitis include Neisseria meningitis and Streptococcus pneumoniae. It can be transmitted by droplets through the airways, with the bacteria using the bloodstream as the main route to reach the blood-brain barrier, and from there to the meninges. There are currently several accurate diagnostic methods, with CSF culture being the gold standard. In addition, the improvement in the quality of beta-lactam treatment and the greater possibility of prevention due to the increased number and effectiveness of vaccines have contributed to reducing the number of cases and severity of the disease. Nevertheless, despite these advances, this syndrome still presents a high number of mortalities and sequelae.

Análisis comparativo de la actividad antimicrobiana de secreciones y excreciones larvarias de Calliphora vicina y Sarconesiopsis magellanica (Diptera: Calliphoridae) / A comparative analysis of Calliphora vicina and Sarconesiopsis magellanica (Diptera: Calliphoridae) larval secretions and excretions antimicrobial activity

Introducción. La creciente resistencia bacteriana a los antibióticos representa una amenaza mundial de salud pública. Las excreciones y secreciones larvarias derivadas de moscas necrófagas de la familia Calliphoridae podrían configurar una fuente promisoria para contrarrestar sus efectos. Objetivo. Comparar la actividad antimicrobiana de las excreciones y secreciones larvarias nativas, y de las mayores y menores de 10 kDa de Calliphora vicina y Sarconesiopsis magellanica (Diptera: Calliphoridae). Materiales y métodos. El bioensayo se hizo a partir de la técnica de turbidimetría y en el caso de las excreciones y secreciones menores de 10 kDa se determinó la concentración inhibitoria mínima (CIM). Resultados. Las excreciones y secreciones nativas y las menores de 10 kDa de C. vicina y S. magellanica, evidenciaron una potente actividad antibacteriana contra tres cepas de Staphylococcus aureus y cuatro bacterias Gram negativas, siendo las menores de 10 kDa más efectivas que las nativas en las dos especies de moscas evaluadas. Además, las menores de 10 kDa presentaron la misma efectividad, aunque en las pruebas de CIM se observó que las de S. magellanica fueron más potentes en todas las bacterias evaluadas, excepto contra la cepa de S. aureus ATCC 25923. Las mayores de 10 kDa no inhibieron el crecimiento bacteriano. Conclusión. Los resultados validaron, en general, que estas sustancias son fuente importante para el aislamiento y la caracterización de agentes antimicrobianos.

Introduction: The growing resistance to antibiotics worldwide represents a global threat to public health. The larval excretions and secretions derived from necrophagous flies from the Calliphoridae family could represent a promising source for counteracting their effects. Objective: To compare the antimicrobial activity of Calliphora vicina and Sarconesiopsis magellanica (Diptera: Calliphoridae) native excretions and secretions and those weighing more than 10 kDa and less. Materials and methods: We used the turbidimetry technique for the bioassay; we determined the minimum inhibitory concentration (MIC) for excretions and secretions weighing less than 10 kDa. Results: Calliphora vicina and S. magellanica native excretions and secretions and those weighing less than 10 kDa exhibited potent antibacterial activity against three Staphylococcus aureus strains and four Gram-negative bacteria; those weighing less than 10 kDa were more effective than the native ones in the two species of flies evaluated here. Furthermore, excretions and secretions weighing less than 10 kDa had the same effectiveness, except in the MIC trials where S. magellanica excretions and secretions weighing less than 10 kDa were more potent against all the bacteria evaluated, except for S. aureus ATCC 25923. Excretions and secretions weighing more than 10 kDa did not inhibit bacterial growth. Conclusions: These results potentially validate these substances as an important source for isolating and characterizing antimicrobial agents.

Probiotics in Crohn's disease remission: a systematic review

Crohn's disease (CD) is an inflammatory condition that can affect the entire gastrointestinal tract due to an exacerbated and inadequate immune system response. Objective. This study aimed to conduct a systematic review, through clinical trials, about the use of probiotics in humans with CD. Materials and methods. Research was carried out in the PubMed, Scopus and Science Direct databases using the keywords "Crohn's disease" and "probiotics". We conducted the review by searching clinical trials published from 2000 to December 2019. Results. Of 2,164 articles found, only nine were considered eligible for this review. The studies investigated patients with CD at different stages of the pathology, and in three studies the potential effect of probiotics in the active phase was observed; in two, in the remission phase; and in four, after intestinal surgery. The sample size of the studies ranged from 11 to 165 individuals and the age of the participants between 5 and 71 years. Gram-positive bacteria were used in six clinical interventions and in two studies yeasts were used. As for the significant results obtained with the treatment with probiotics, in one study there was beneficial clinical effects in patients and, in another, there was an improvement in intestinal permeability. Conclusion. Currently, it is not possible to establish a recommendation for probiotic therapy to control CD due to the few clinical trials with significant results. There is a need for more research on clinical intervention with probiotics in CD to clarify the action, define doses and time of use(AU)

La enfermedad de Crohn (EC) es una afección inflamatoria que puede afectar todo el tracto gastrointestinal debido a una respuesta del sistema inmunitario exacerbada e inadecuada. Objetivo. Realizar una revisión sistemática, a través de ensayos clínicos, sobre el uso de probióticos en humanos con EC. Materiales y métodos. La investigación se realizó en las bases de datos PubMed, Scopus y Science Direct utilizando las palabras clave "enfermedad de Crohn" y "probióticos". La revisión se hizo en ensayos clínicos publicados desde 2000 hasta diciembre 2019. Resultados. De 2164 artículos encontrados, solo nueve fueron considerados elegibles. Los estudios investigaron pacientes con EC en diferentes etapas de la patología, y en tres estudios se observó el efecto potencial de los probióticos en la fase activa; en dos, en remisión; y en cuatro, tras cirugía intestinal. El tamaño de la muestra fue entre 11 y 165 individuos y la edad entre 5 y 71 años. Se utilizaron bacterias grampositivas en seis intervenciones clínicas y en dos estudios se utilizaron levaduras. En cuanto a los resultados significativos obtenidos con el tratamiento con probióticos, en un estudio hubo efectos clínicos beneficiosos en los pacientes y, en otro, hubo una mejora en la permeabilidad intestinal. Conclusión. Actualmente, no es posible establecer una recomendación de terapia con probióticos para el control de la EC debido a los pocos ensayos clínicos con resultados significativos. Existe la necesidad de más investigación sobre la intervención clínica con probióticos en EC para aclarar la acción, definir dosis y tiempo de uso(AU)

Synthesis, antimicrobial and antioxidant activities of pyridyl substituted thiazolyl triazole derivatives

In this present study, 63 different 5-[4-methyl-2-(pyridin-3/4-yl)thiazole-5-yl]-4-substituted-3-substituted benzylthio-4H-1,2,4-triazole derivatives were synthesized, and evaluated for their in vitro antimicrobial activity against various human pathogenic microorganisms and antioxidant activity. The derivatives were synthesized in a multi-step synthesis procedure including triazole and thiazole ring closure reactions, respectively. The synthesized derivatives (A1-24; B1-39) were screened for their antibacterial, antifungal, and antioxidant activities compared to standard agents. The derivatives possessing 3-pyridyl moiety particularly exhibited relatively high antibacterial activity (MIC= < 3.09-500 µg/mL) against Gram-positive bacteria, and compounds possessing 4-pyridyl moiety showed remarkable antioxidant activity

Green synthesis of silver nanoparticles using leaf extracts of Mentha arvensis Linn. and demonstration of their in vitro antibacterial activities

Abstract A study was carried out to synthesize silver nanoparticles (Ag-NPs) using plant extracts and to explore their pharmaceutical application as antibacterial agents. Dried leaves of Mentha arvensis Linn. were powdered and extracts were prepared using three different organic solvents. Preliminary screening on antibacterial activity by agar well diffusion method indicated that the methanolic extract possessed higher potential than the other two. Phytochemical analysis of the leaf extract revealed that it possesses tannins, steroids, terpenoids and flavonoids. Ag-NPs prepared using this extract were of spherical to cuboidal shape ranging in size from 40 to 70 nm. It retained essential chemical groups and had the required surface plasmon resonance. Further to the antimicrobial assay, the Ag-NPs, in contrast to the whole methanolic leaf extract, showed better (100% vs. 80%) bactericidal activity against the indicator organisms. The zones of growth inhibition for gram positive bacteria ranged between 14±0.6 and 23±0.3, while it was between 12±0.6 and 22±0.2 for gram negative bacteria. The Ag-NPs presented the minimum inhibitory concentration values of 250 µg/mL for gram positive bacteria and 250 - 500 µg/mL for gram negative bacteria. These findings suggest that the natural compounds present in M. arvensis L. possess the potency to facilitate the synthesis and antibacterial action of Ag-NPs.

Interações populacionais mediadas por quorum sensing na microbiota do soro-fermento utilizado na produção do queijo Canastra / Population interactions mediated by quorum sensing in the microbiota of the endogenous culture used in the production of canasta cheese

Bactérias regulam a expressão de diversos fenótipos de acordo com a sua densidade populacional, em um comportamento conhecido como quorum sensing. Em micro-organismos de origem alimentar, o quorum sensing pode influenciar na formação de biofilmes, produção de toxinas e de enzimas hidrolíticas. Em bactérias Gram-negativas a sinalização é normalmente mediada por moléculas de N-acilhomoserina lactona (AHLs), conhecidas por autoindutor 1 (AI-1). Estudos revelam a inibição do quorum sensing nestas bactérias por enzimas que degradam as AHLS, em um processo denominado quorum quenching. Tipicamente brasileiro, o queijo Canastra é um produto artesanal maturado, produzido a partir de leite cru e do pingo, um tipo de soro-fermento coletado e utilizado diariamente na produção. A composição microbiana do pingo é diversificada e característica da região produtora. Essa combinação de bactérias, única em cada queijaria, resulta em aroma e textura típicos. Enquanto a microbiota Gram-positiva contribui para o desenvolvimento de sabor, textura e aroma no produto, bactérias Gram-negativas nesses queijos são geralmente associadas à formação de olhaduras, aromas desagradáveis, má coagulação da massa e até à patogenicidade. Este trabalho visou analisar a interação entre a microbiota Gram-positiva e Gram-negativa presente no pingo pela detecção dos sistemas de quorum sensing e quorum quenching nas amostras. A presença de AHLs foi avaliada em 45 amostras de pingo, a partir da extração em acetato de etila acidificado e da avaliação dos extratos por meio de bioensaios com Agrobacterium tumefaciens WCF47(pCF218)(pCF372) e KYC55(pJZ410)(pJZ372)(pJZ384), resultando em apenas uma amostra positiva. Em seguida, 350 isolados foram obtidos a partir de 11 amostras de pingo, sendo 200 isolados classificados como Gram-positivos e 150 Gram-negativos. Os Gramnegativos foram avaliados quanto à produção de AHLs in vitro através de ensaio em placa utilizando as estirpes biossensoras A. tumefaciens WCF47(pCF218)(pCF372), Chromobacterium violaceum CV026 e Escherichia coli pSB403, resultando em 39 isolados produtores de AHLs, provenientes de 10 pingos diferentes. Já os isolados Gram-positivos foram analisados quanto à capacidade de inibição do QS utilizando as estirpes biossensoras C. violaceum CV026 e A. tumefaciens WCF47(pCF218)(pCF372), em meio suplementado com C6-HSL ou 3-oxo-C12-HSL. Foi detectada a inibição total da resposta ao quórum por 78 isolados testados, enquanto a inibição parcial foi provocada por outros 63. A inibição do crescimento das estirpes biossensoras também foi observada para 24 isolados. Os isolados promotores de inibição parcial foram recultivados em meio mínimo com C6-HSL ou 3-oxo-C12-HSL como únicas fontes de carbono. Foram recuperados 28 isolados, e a ação desses sobre diferentes substratos foi avaliada, resultando em 22 isolados produtores de lactonases e 6 produtores de acilase. Os 39 isolados Gram-negativos e os 28 isolados Gram-positivos finais foram identificados por MALDI-TOF MS, resultando, segundo o conhecimento do autor, no primeiro relato de produção de AHLs por Pseudomonas fulva, Enterobacter xiangfangensis e Lelliottia amnigena, bem como a produção de lactonases por Staphylococcus xylosus e a produção de acilase por S. aureus, Microbacterium maritypicum e Rothia kristinae. Este trabalho mostrou que interações populacionais mediadas por quorum sensing dependente de AHLs na microbiota do soro-fermento são possíveis. Porém, essas interações estão propensas a serem inibidas por meio de lactonases e acilases produzidas por parte das bactérias Gram-positivas

Bacteria regulate the expression of different phenotypes according to their population density, in a behavior known as quorum sensing. In food-borne microorganisms, quorum sensing can influence the formation of biofilms, production of toxins and hydrolytic enzymes. In Gram-negative bacteria, signaling is normally mediated by Nacyl homoserine lactone molecules (AHLs), known as autoinducer 1 (AI-1). Studies reveal the inhibition of quorum sensing in these bacteria by enzymes that degrade AHLS, in a process called quorum quenching. Typically Brazilian, Canastra cheese is a matured artisanal product, produced from raw milk and pingo, a type of endogenous culture collected and used daily in production. The microbial composition of pingo is diverse and characteristic of the producing region. This combination of bacteria, unique in each cheese factory, results in a typical aroma and texture. While the Gram-positive microbiota contributes to the development of flavor, texture and aroma in the product, Gram-negative bacteria in these cheeses are generally associated with the formation of eyes, off-flavors, poor curd coagulation and even pathogenicity. Thus, this work aimed to analyze the interaction between the Gram-positive and Gram-negative microbiota present in this culture by detecting quorum sensing and quorum quenching systems in the samples. The presence of AHLs was evaluated in 45 samples of pingo, with extraction with acidified ethyl acetate and the evaluation of the extracts through bioassays with Agrobacterium tumefaciens WCF47(pCF218)(pCF372) and KYC55(pJZ410)(pJZ372)(pJZ384 ), resulting in only one positive sample. Then, 350 isolates were obtained from 11 endogenous culture samples, with 200 being classified as Gram-positive and 150 Gram-negative. Gram-negatives were evaluated for the production of AHLs in vitro by plaque assay using the biosensor strains A. tumefaciens WCF47(pCF218)(pCF372), Chromobacterium violaceum CV026 and Escherichia coli pSB403, resulting in 39 AHL-producing isolates from 10 different samples. Gram-positive isolates were analyzed for their ability to inhibit quorum sensing using biosensor strains C. violaceum CV026 and A. tumefaciens WCF47(pCF218)(pCF372), in medium supplemented with N-hexanoyl-L-homoserine lactone or 3-oxo-dodecanoyl-Lhomoserine lactone. Total inhibition of the quorum response was detected by 78 tested isolates, while partial inhibition was caused by 63. Growth inhibition of biosensor strains was also observed for 24 isolates. Partial inhibition promoter isolates were recultured on minimal medium with C6-HSL or 3-oxo-C12-HSL as sole carbon sources. Twenty-eight isolates were recovered, and the action of these isolates on different substrates was evaluated, resulting in 22 lactonase producers and 6 acylase producers. The 39 Gram-negative isolates and the final 28 Grampositive isolates were identified by MALDI-TOF MS, resulting, to the best of the author's knowledge, in the first report of AHL production by Pseudomonas fulva, Enterobacter xiangfangensis and Lelliottia amnigena, as well as the lactonase production by Staphylococcus xylosus and acylase production by S. aureus, Microbacterium maritypicum and Rothia kristinae. This work demonstrated that population interactions mediated by AHLs-dependent quorum sensing in Canastra cheese endogenous culture microbiota are possible. However, these interactions are prone to inhibition by lactonases and acylases produced by Gram-positive bacteria

Infecção primária da corrente sanguínea associada ao cateter venoso central em neonatos / Infección primaria del torrente sanguíneo asociada al catéter venoso central en neonatos resumen / Central venous catheter-associated primary bloodstream infection in neonates

RESUMO Objetivo: analisar a infecção primária da corrente sanguínea associada ao cateter venoso central em neonatos internados em unidades de terapia intensiva. Método: tratou-se de um estudo ecológico realizado em 2017 a partir de notificações de infecção primária da corrente sanguínea associada ao cateter venoso central ocorridas na capital de um estado da região Centro-Oeste do Brasil. Os dados foram coletados por meio de um formulário a partir de dois bancos de dados, municipal (2012 a 2016) e nacional (2014 a 2016). Resultados: a tendência temporal da densidade de incidência de infecção foi decrescente (p=0,019), com taxa de utilização de cateter venoso central de 45%. Os patógenos mais frequentes foram Klebsiella pneumoniae, Staphylococcus coagulase negativo e Enterobacter spp. Aumento de resistência às cefalosporinas e à oxacilina ocorreu para bactérias Gram-negativo e Gram-positivo, respectivamente. Conclusão: Conclui-se que houve uma redução na taxa de IPCS associada ao cateter em neonatos no período avaliado e os episódios infecciosos foram predominantemente causados por bactérias Gram-negativo, incluindo isolados multirresistentes aos antimicrobianos. Esses achados apontam para a importância e necessidade de estratégias educacionais para a equipe multiprofissional sobre vigilância de infecção, medidas preventivas e uso racional de antimicrobianos.

Resumen: Objetivo: analizar la infección primaria del torrente sanguíneo asociada al catéter venoso central en neonatos ingresados en unidades de cuidados intensivos. Método: se trató de un estudio ecológico, realizado en 2017, a partir de notificaciones de infección primaria del torrente sanguíneo asociada al catéter venoso central, ocurridas en la capital de un estado de la región Centro-Oeste de Brasil. Los datos fueron recogidos por medio de un formulario de dos bases de datos, municipal (2012 a 2016) y nacional (2014 a 2016). Resultados: la tendencia temporal de la densidad de incidencia de infección fue decreciente (p=0,019), con tasa de utilización de catéter venoso central del 45%. Los patógenos más frecuentes fueron Klebsiella pneumoniae, Staphylococcus coagulase negativa y Enterobacter spp. Aumento de resistencia a las cefalosporinas y a la oxacilina ocurrió para bacterias Gramnegativas y Grampositivas, respectivamente. Conclusión: hubo una reducción en la tasa de infección primaria del torrente sanguíneo asociada al catéter en neonatos en el período evaluado, y los episodios infecciosos fueron predominantemente causados por bacterias gramnegativas, incluyendo aislados multirresistentes a los antimicrobianos. Estos hallazgos señalan la importancia y necesidad de estrategias educativas para el equipo multiprofesional sobre vigilancia de infecciones, medidas preventivas y uso racional de antimicrobianos.

ABSTRACT Objective: to analyze primary bloodstream infections associated with central venous catheter in neonates admitted to intensive care units. Method: ecological study, conducted in 2017, from reports of primary bloodstream infections associated with central venous catheter, which occurred in the capital of a state in the Midwest region of Brazil. Data were collected using a form from two databases, municipal (2012 to 2016) and national (2014 to 2016). Results: the temporal trend of the infection incidence density was decreasing (p=0.019), with a central venous catheter use rate of 45%. The most frequent pathogens were Klebsiella pneumoniae, Coagulase-negative staphylococci, and Enterobacter spp. Increased resistance to cephalosporins and oxacillin occurred for Gram-negative and Gram-positive bacteria, respectively. Conclusion: There was a reduction in the rate of catheter-associated primary bloodstream infection in neonates in the period evaluated, and the infectious episodes were predominantly caused by Gram-negative bacteria, including antimicrobial multi-resistant isolates. These findings point to the importance and need for educational strategies for the multiprofessional team on infection surveillance, preventive measures, and rational use of antimicrobials.

The extracellular vesicles from gram-positive bacteria: a review / 生物工程学报

Extracellular vesicles (EVs), also known as membrane vesicles, are vesicular bodies secreted by eukaryotic cells and bacteria. EVs can carry proteins, DNA, RNA, and various metabolites for the exchange and transmission of substances between cells. They play contents-dependent physiological functions, such as delivering nutrients, participating in immune response, and treating cancers. Currently, most studies focus on the exploration of vesicles secreted by eukaryotic cells and gram-negative bacteria, while few studies focus on gram-positive bacteria. This review summarized the production, content composition, physiological function, and engineering of EVs secreted by gram-positive bacteria, and prospected future perspectives in this area.

Bacteremia after Bacillus clausii administration for the treatment of acute diarrhea: A case report / Bacteriemia tras la administración de Bacillus clausii para el tratamiento de la diarrea aguda: reporte de un caso

Abstract | Bacillus clausii is a gram-positive rod used as a probiotic to treat diarrhea and the side effects of antibiotics such as pseudomembranous colitis. We report a case of B. clausii bacteremia in a non-immunocompromised patient with active peptic ulcer disease and acute diarrhea. The probiotic was administered during the patient's hospitalization due to diarrhea of infectious origin. B. clausii was identified in the bloodstream of the patient through Matrix- Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF) days after her discharge. Given the wide use of probiotics, we alert clinicians to consider this microorganism as a causative agent when signs of systemic infection, metabolic compromise, and hemodynamic instability establish after its administration and no pathogens have been identified that could explain the clinical course.

Resumen | Bacillus clausii es un bacilo Gram positivo usado como probiótico para tratar la diarrea y efectos adversos de los antibióticos, como la colitis pseudomembranosa. Se reporta un caso de bacteriemia por B. clausii en una paciente inmunocompetente con enfermedad ulcerosa péptica activa y diarrea aguda. El probiótico le fue administrado durante la hospitalización debido al origen infeccioso de la diarrea. B. clausii se identificó en el torrente sanguíneo de la paciente, utilizando espectrometría de desorción/ionización mediante láser asistido por matriz (Matrix-Assisted Laser Desorption/Ionization, MALDI), acoplada a un detector de iones (Time of Flight, TOF) (MALDI-TOF), días después de haber sido dada de alta. Dado el amplio uso de los probióticos, alertamos a los clínicos para que consideren este microorganismo como agente causal cuando se detecten signos de infección sistémica, compromiso metabólico, e inestabilidad hemodinámica tras su administración, y no se haya identificado ningún patógeno que pueda explicar el cuadro clínico.

Evaluación del efecto antibacteriano sinérgico de rifamicina en propóleo sobre bacterias grampositivas / Evaluation of the synergistic antibacterial effect of rifamycin in propolis on gram-positive bacteria

Introducción: En la medicina militar, la aplicación de las sustancias antibacterianas en las infecciones tópicas, es importante en el tratamiento de las tropas. Objetivos: Evaluar el efecto antibacteriano sinérgico de rifamicina en propóleo sobre bacterias grampositivas. Métodos: Estudio experimental in vitro y comparativo. Se efectuó el análisis fitoquímico preliminar del propóleo de Apis mellífera. Se utilizaron 96 placas de agar Muller Hinton (Britania®) (48 placas para cada especie bacteriana) repartidas en 6 grupos (n = 8). grupo I (agua destilada), grupo II (alcohol etílico al 96 por ciento), grupo III (rifamicina al 0,5 por ciento), grupo IV (rifamicina al 1 por ciento), grupo V (propóleo al 20 por ciento) y grupo VI (rifamicina al 1 por ciento en propóleo al 40 por ciento); se empleó la metodología de Kirby - Bauer; las cepas usadas fueron Staphylococcus aureus ATCC 25923, Streptococcus pyogenes ATCC 19615 y las mediciones de las zonas de inhibición se efectuaron a las 24 horas. Resultados: Se detectaron compuestos fenólicos, taninos, flavonoides, alcaloides y triterpenoides en propóleo. Se comprobó el efecto antibacteriano del grupo V con 18,627 ± 0,1008 mm (92,59 por ciento) y 19,247 ± 0,0762 mm (96,74 por ciento), y el efecto antibacteriano sinérgico del grupo VI con 19,316 ± 0,1202 mm (96,02 por ciento) y 19,613 ± 0,0820 mm (98,58 por ciento), comparados con rifamicina al 1 por ciento (100 por ciento) sobre S. aureus ATCC 25923 y S. pyogenes ATCC 19615. Conclusiones: La combinación de rifamicina al 1 por ciento unida al propóleo al 40 por ciento presenta una mayor actividad antibacteriana in vitro sobre bacterias grampositivas debido a su efecto sinérgico(AU)

Introduction: In military medicine, the application of antibacterial substances in topical infections are important in the treatment of troops. Objectives: To evaluate the synergistic antibacterial effect of rifamycin in propolis on gram-positive bacteria. Methods: In vitro and comparative experimental study. Preliminary phytochemical analysis of Apis mellifera propolis was carried out. 96 Muller Hinton agar plates (Britania®) (48 plates for each bacterial species) divided into 6 groups (n = 8) were used group I (distilled water), group II (96 percent ethyl alcohol), group III (rifamycin 0,5 percent), group IV (rifamycin 1 percent), group V (propolis 20 percent) and group VI (rifamycin 1 percent in 40 percent propolis); Kirby-Bauer methodology was used; the strains used were Staphylococcus aureus ATCC 25923, Streptococcus pyogenes ATCC 19615 and the measurements of the zones of inhibition were carried out at 24 hours. Results: Phenolic compounds, tannins, flavonoids, alkaloids and triterpenoids were detected in propolis. The antibacterial effect of group V was verified with 18,627 ± 0,1008 mm (92,59 percent) and 19,247 ± 0,0762 mm (96,74 percent), and the synergistic antibacterial effect of group VI with 19,316 ± 0,1202 mm (96,02 percent) and 19,613 ± 0,0820 mm (98,58 percent), compared with rifamycin 1 percent (100 percent) on S. aureus ATCC 25923 y S. pyogenes ATCC 19615. Conclusions: The combination of rifamycin 1 percent together with propolis 40 percent has a greater antibacterial activity in vitro on gram-positive bacteria due to its synergistic effect(AU)

Action of benzalkonium chloride in different pH

Ammonium quaternary compounds are widely used in poultry and swine production as disinfectants in the control of pathogens. They act on gram-positive bacteria, gram-negative bacteria, enveloped fungi and viruses. However, in some conditions of pH and presence of organic matter can be inactivated. This study evaluated the action of ammonium quaternary compounds at 1:1,000 and 1:2,000 dilutions against Salmonella enterica serovarTyphimurium and Salmonella enterica serovar Enteritidis in the presence of three different organic matter simulators, fetal bovine serum, skim milk and whole milk concentration of 1, 3, 5, and 7% and at pH 6 and 9, with 15 min of contact. It was possible to verify that the organic matter simulators adjusted in the same conditions of contact time and percentage, in the in vitro tests, presented different results and the fetal bovine serum did not inactivate the disinfectant. However, the best result against S. Typhimurium and S. Enteritidis was obtained at pH 6 at the dilution of 1:1,000 in all organic matter simulators.

Disparities in antimicrobial consumption and resistance within a country: the case of beta-lactams in Argentina / Disparidades en el consumo de antimicrobianos y la resistencia a estos dentro de un país: el caso de los betalactámicos en Argentina / Disparidades internas no consumo e na resistência aos antimicrobianos: o caso dos betalactâmicos na Argentina

ABSTRACT Objective. To describe bacterial resistance and antimicrobial consumption ratio at the subnational level in Argentina during 2018, considering beta-lactams group as a case-study. Methods. Antimicrobial consumption was expressed as defined daily doses (DDD)/1000 inhabitants. Resistance of Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus to beta-lactams was recorded. Resistance/consumption ratio was estimated calculating "R" for each region of Argentina, and this data was compared with other countries. Results. The most widely consumed beta-lactams in Argentina were amoxicillin (3.64) for the penicillin sub-group, cephalexin (0.786) for first generation cephalosporins, cefuroxime (0.022) for second generation; cefixime (0.043) for third generation and cefepime (0.0001) for the fourth generation group. Comparison between beta-lactams consumption and bacterial resistance demonstrated great disparities between the six regions of the country. Conclusions. The case-study of Argentina shows that antimicrobial consumption and resistance of the most common pathogens differed among regions, reflecting different realities within the same country. Because this situation might also be occurring in other countries, this data should be taken into account to target local efforts towards better antimicrobial use, to improve antimicrobial stewardship programs and to propose more suitable sales strategies in order to prevent and control antimicrobial resistance.

RESUMEN Objetivo. Determinar la razón entre la resistencia bacteriana y el consumo de antimicrobianos a nivel subnacional en Argentina en el 2018, considerando el grupo de los betalactámicos como estudio de caso. Métodos. El consumo de antimicrobianos se expresó como una dosis diaria determinada (DDD) por 1000 habitantes. Se registró la resistencia de Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae y Staphylococcus aureus a los betalactámicos. Se determinó la razón entre la resistencia y el consumo calculando "R" para cada región de Argentina, y estos datos se compararon con los de otros países. Resultados. Los betalactámicos más consumidos en Argentina fueron la amoxicilina (3,64) para el subgrupo de la penicilina; la cefalexina (0,786) para las cefalosporinas de primera generación; la cefuroxima (0.022) para las de segunda generación; la cefixima (0.043) para las de tercera generación, y la cefepima (0.0001) para el grupo de la cuarta generación. La comparación entre el consumo de betalactámicos y la resistencia bacteriana demostró que había grandes disparidades entre las seis regiones del país. Conclusiones. El estudio de caso en Argentina indica que el consumo de antimicrobianos y la resistencia a los patógenos más comunes difería entre las regiones; esto demuestra que hay distintas realidades dentro del mismo país. Como esta situación también se puede dar en otros países, estos datos se deben tener en cuenta para definir las actividades locales destinadas a fomentar un mejor uso de los antimicrobianos, para mejorar los programas de manejo de los antimicrobianos y para proponer estrategias de venta más adecuadas con el fin de prevenir y controlar la resistencia a los antimicrobianos.

RESUMO Objetivo. Descrever a relação entre o consumo de antimicrobianos e a resistência bacteriana no nível subnacional na Argentina em 2018, considerando o grupo dos betalactâmicos no estudo de caso. Métodos. O consumo de antimicrobianos foi representado por doses diárias definidas (DDD) por 1.000 habitantes. Foi registrada a resistência de Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae e Staphylococcus aureus aos betalactâmicos. A relação entre consumo e resistência foi calculada com base no "R" para cada região do país e os dados da Argentina foram comparados aos de outros países. Resultados. Os betalactâmicos de maior consumo na Argentina foram amoxicilina (3,64) no grupo das penicilinas, cefalexina (0,786) no grupo das cefalosporinas de primeira geração, cefuroxima (0.022) no grupo das cefalosporinas de segunda geração, cefixima (0.043) no grupo das cefalosporinas de terceira geração e cefepima (0.0001) no grupo das cefalosporinas de quarta geração. Ao se comparar o consumo de betalactâmicos e a resistência bacteriana, observou-se grande disparidade entre as seis regiões do país. Conclusões. O estudo de caso revela diferenças no consumo de antimicrobianos e na resistência dos patógenos mais comuns entre as regiões da Argentina, refletindo realidades distintas dentro do mesmo país. Como esta mesma situação pode estar ocorrendo em outros países, estes achados devem servir para direcionar os esforços locais a uma melhor utilização dos antimicrobianos, aperfeiçoar os programas de gestão do uso destes medicamentos e propor estratégias de venda mais apropriadas, visando a prevenir e controlar a resistência aos antimicrobianos.

Diseño, estandarización e implementación de una nueva técnica en Guatemala, para el diagnóstico rápido de hemocultivos positivos, utilizando la tecnología Maldi-tof / Design, standardization and implementation of a new technique in Guatemala, for the rapid diagnosis of positive blood cultures, using Maldi-tof technology

Las enfermedades infecciosas son un problema de salud que a pesar de los avances médicos siguen cobrando vi-das en todo el mundo; como las septicemias. La presente investigación tuvo por objetivo diseñar, estandarizar e implementar un protocolo inexistente en Guatemala, para el diagnóstico rutinario de hemocultivos positivos dentro de las instalaciones del Laboratorio Clínico del Hospital General San Juan de Dios, lugar en donde se encuentra el único espectrómetro de masas de tipo Maldi-tof (Matrix Assisted Laser Desorption Ionization-Time of flight-mass spectrometry).Se utilizaron 240 muestras de pacientes de los diferentes servicios. El diagnóstico se realizó compa-rando las identificaciones obtenidas a partir de cultivos microbiológicos puros con muestras directas de botellas con caldo BHI(Brain Heart Infusion).Los resultados de las dos metodologías fueron evaluados con el diseño estadístico "apareado o emparejado en grupo". La comparación no evidenció discordancia en las identificaciones; pero sí en los tiempos de respuesta. La reducción de tiempo fue de 42.9 h para bacterias Gram positivo, 45.0 h para bacterias Gram negativo y 126.2 h para levaduras, todos a favor de identificaciones a partir de muestras directas. Con esta investigación se pretende ofrecer una nueva alternativa que permitirá brindar un diagnóstico rápido, confiable y certero a la población guatemalteca. También permitirá reducir la morbimortalidad de los pacientes con septicemias, promover el ahorro de insumos hospitalarios, disminuir el tiempo de estancia hospitalaria, ahorrar el consumo de antibióticos innecesarios y contribuir indirectamente a combatir la resistencia antimicrobiana; un problema actual de gran importancia a nivel mundial.

Infectious diseases are a health problem that despite medical advances in terms of diagnosis continue to take lives worldwide, such is the case of sepsis. The purpose of this research was to design, standardize and implement a non-existent protocol in Guatemala, for the routine diagnosis of positive blood cultures, within the facilities of the clinical laboratory of the San Juan de Dios General Hospital; where the only Maldi-tof (Matrix Assisted Laser Desorp-tion Ionization-Time of flight-mass spectrometry) type mass spectrometer is located. For this, 240 samples of positive blood cultures were used, coming from patients of the different services. The microbiological diagnosis was made by comparing the identification data obtained from pure microbiological cultures and direct samples of BHI broth (Brain Heart Infusion) bottles. The results of the two methodologies were evaluated based on "paired or matched in groups" statistical design. The Maldi-tof technique did not show disagreement regarding identification between the two types of samples; but it did in the response time. The time reduction was 42.9 h for Gram positive bacteria, 45.0 h for Gram negative and 126.2 h for yeasts, supporting identification from direct samples. This research aims to provide a new diagnostic alternative that will allow access to fast, reliable, and accurate results for the Guatemalan population. It will also help to reduce e morbidity and mortality rates of patients with sepsis, to promote hospital supplies savings, decrease the patient length of stay, save unnecessary antibiotics and indirectly contribute to combating antimicrobial resistance; a critical problem faced by the world today.

What Are the Roles of Carbapenems in an Institution-specific Epidemiological Antibiogram in East Trinidad?

ABSTRACT Objective: To provide an overview of the development of an institution-specific epidemiological antibiogram. Emphasis was on last-line antibiotics, such as carbapenems. Methods: In 2013, the antibiograms of various organisms were retrieved from the computerized database of the Microscan (Siemens Healthcare) at the Microbiology Laboratory of the Sangre Grande Hospital in East Trinidad, West Indies. These were divided into blood and urine specimen antibiograms. All the wards and hospital clinics were included. A 20% cut-off was used to determine that a particular antibiotic or antibiotic class could be used for empiric therapy. All the organisms were not chosen. Only the most common and clinically relevant organisms were chosen. Results: Blood: Escherichia coli, Klebsiella pneumonia, Proteus mirabilis: Imipenem, mero- penem, ertapenem showed greater than 80% sensitivity, respectively. Pseudomonas aeruginosa: ceftazidime, ciprofloxacin, gentamicin, levofloxacin and tazobactam/piperacillin showed 100%, 80%, 80%, 100% and 100% sensitivity, respectively. Urines: E. coli, Klebsiella pneumonia, Proteus mirabilis: Imipenem, meropenem, ertapenem, were greater than 80% sensitive. Enterobacter cloacae: Imipenem, meropenem were 92%, 100% sensitive. Pseudomonas aeruginosa: tazobactam-piperacillin and amikacin were both 85% susceptible. Acinetobacter baumanii/haemolyticus: All the antibiotics were above the 20% resistance threshold. Conclusion: Patient-specific antibiograms and unit-specific trends (eg, ICU, surgical wards and outpatient clinic) can be used as a guide in patients with less severe infections. Carbapenems can still be used empirically, in East Trinidad, for sepsis.

Desenvolvimento e validação de um aplicativo móvel para identificação de bactérias Gram-positivas e Gram-negativas / Development and validation of a mobile application to identify Gram-positive and Gram-negative bacteria

Objetivo: A internet e os smartphones estão fortemente presentes no cotidiano mundial. Além de proporcionarem comunicação e lazer, os smartphones, por meio de aplicativos, são portas de entrada para as tecnologias da informação e comunicação, recursos utilizados por docentes e discentes como metodologia científica de ensino-aprendizado. Além disso, atuam como ferramenta de apoio para profissionais. As evoluções científicas também abrangem a microbiologia clínica, onde é possível observar a inclusão de recursos tecnológicos com o objetivo de minimizar o tempo de análise e assegurar a qualidade dos resultados; entretanto, a automatização ainda é uma realidade distante em muitos laboratórios do Brasil, portanto, o objetivo desta pesquisa foi desenvolver e validar a funcionalidade de um aplicativo como ferramenta de apoio para discentes e profissionais de microbiologia clínica. Métodos: Pesquisa metodológica, aplicada e de produção tecnológica, realizada de abril a outubro de 2019. Foi escolhida a metodologia de Galvis-Panqueva, que compõe as etapas de construção e validação. Ao final das etapas que compõem a validação, 16 discentes da Ulbra Canoas e oito profissionais de microbiologia clínica avaliaram o aplicativo quanto às percepções como usuários. Após esta avaliação, obteve-se o Índice de Validade de Conteúdo. Resultados: O Índice de Validade de Conteúdo entre os profissionais foi de 0,97 e entre os discentes foi de 0,94, valores aceitáveis para validação. Conclusão: Os resultados atingiram o objetivo proposto e corrobora com demais pesquisas da mesma linha metodológica. O aplicativo atendeu aos critérios de desenvolvimento e validação e mostrou-se uma boa ferramenta de apoio para discentes e profissionais de microbiologia clínica.

Objective: The internet and smartphones are strongly present in the daily world. In addition to providing communication and leisure, smartphones, through applications, are the gateway to Information and Communication Technologies, a resource used by teachers and students as a scientific teaching-learning methodology. In addition, they act as a support tool for professionals. Scientific developments also include clinical microbiology, where it is possible to observe the inclusion of technological resources in order to minimize the analysis time and ensure the quality of the results. However, automation is still a distant reality in many laboratories in Brazil, therefore, the objective of this research was to develop and validate the functionality of an application as a support tool for students and professionals in clinical microbiology. Methods: Methodological, applied and technological production research, carried out from April to October 2019. The GalvisPanqueva methodology was chosen, which comprises the stages of construction and validation. At the end of the steps that make up the validation, 16 students from the Ulbra Canoas and eight professionals of clinical microbiology evaluated the application regarding their perceptions as users. Afterwards, the Content Validity Index was obtained. Results: The Content Validity Index among professiona was 0,97 and among students it was 0,94, acceptable values for validation. Conclusion: The results achieved the proposed objective and corroborates with other researches of the same methodological line. The application met the development and validation criteria and proved to be a good support tool for students and professionals in clinical microbiology.

Carbapenem-resistant bacilli in a hospital in southern Brazil: prevalence and therapeutic implications

Abstract Background Gram-negative bacilli (GNB), notably Acinetobacter spp., Pseudomonas spp., and Klebsiella spp., are becoming increasingly resistant to carbapenems and are associated with high health care costs and mortality, becoming a global concern. Objective To determine the prevalence rates of carbapenem resistance among Acinetobacter spp., Pseudomonas spp., and Klebsiella spp. in the main sites of nosocomial infection at a tertiary care hospital in southern Brazil and the consequent therapeutic implications. Methods Cultures processed at the institution's laboratory in 2017 were analyzed, and those positive for Acinetobacter spp., Pseudomonas spp., and Klebsiella spp. were identified. Antibiograms were evaluated for meropenem sensitivity following the Clinical Laboratory Standards Institute guidelines. Results Acinetobacter spp. had the lowest prevalence among the three GNB, and resistance of this pathogen to meropenem at different sites of infection ranged from 36% (blood) to 82% (respiratory tract). Pseudomonas spp. was highly prevalent at the respiratory tract (31%) and had a high resistance rate to meropenem in rectal swab samples (71%), but a relatively low frequency at infection sites (skin/soft tissue, 13%; blood, 25%). Klebsiella spp. was identified in 7.5% of the blood cultures and 15% of the urine cultures and was the chief colonizer among all pathogens, representing 54% of all rectal swab samples, of which 53% were meropenem resistant. At sites of infection, rates of Klebsiella spp. resistant to meropenem ranged from 19% (skin) to 55% (vascular catheter). Conclusions The prevalence of carbapenem-resistant GNB at our hospital was relatively low compared to national and international data; thus, meropenem remains a good therapeutic option against these bacteria. Other antibiotics effective against GNB, such as ceftazidime, cefepime, and piperacillin-tazobactam, can be used in most cases, while meropenem should be reserved for patients with sepsis. Strict contact precaution measures are still needed, given the high resistance rate observed at the colonizing site.

A vancomicina administrada na dose empírica garante a cobertura de pacientes pediátricos contra patógenos Gram-positivos? / Does vancomycin administered at an empirical dose ensure coverage of pediatric patients against gram-positive pathogens?

RESUMO Objetivo: Investigar a efetividade da vancomicina contra Gram-positivos com concentração inibitória mínima de 1mg/L em pacientes pediátricos com base na razão entre área sob a curva e concentração inibitória mínima > 400. Métodos: População de 22 pacientes pediátricos (13 meninos) internados no centro de terapia intensiva pediátrica, com função renal preservada, que foram distribuídos em dois grupos (G1 < 7 anos e G2 ≥ 7 anos). Após a quarta dose de vancomicina (10 - 15mg/kg a cada 6 horas), duas amostras de sangue foram colhidas (terceira e quinta horas), seguidas da dosagem sérica por imunoensaios para investigação da farmacocinética e da cobertura do antimicrobiano. Resultados: Não se registrou diferença entre os grupos com relação à dose, ao nível de vale ou ainda na área sob a curva. A cobertura contra Gram-positivos com concentração inibitória mínima de 1mg/L ocorreu em apenas 46% dos pacientes em ambos os grupos. A farmacocinética se mostrou alterada nos dois grupos diante dos valores de referência, mas a diferença entre grupos foi registrada pelo aumento da depuração total corporal e pelo encurtamento da meia-vida biológica, mais pronunciados nos pacientes mais novos. Conclusão: A dose empírica mínima de 60mg/kg ao dia deve ser prescrita ao paciente pediátrico de unidade de terapia intensiva com função renal preservada. A utilização da razão entre área sob a curva e concentração inibitória mínima na avaliação da cobertura da vancomicina é recomendada para se atingir o desfecho desejado, uma vez que a farmacocinética está alterada nesses pacientes, podendo impactar na efetividade do antimicrobiano.

Abstract Objective: To investigate the vancomycin effectiveness against gram-positive pathogens with the minimum inhibitory concentration of 1mg/L in pediatric patients based on the area under the curve and the minimum inhibitory concentration ratio > 400. Methods: A population of 22 pediatric patients (13 boys) admitted to the pediatric intensive care unit with preserved renal function was stratified in two groups (G1 < 7 years and G2 ≥ 7 years). After the fourth dose administered of vancomycin (10 - 15mg/kg every 6 hours) was administered, two blood samples were collected (third and fifth hours), followed by serum measurement by immunoassays to investigate the pharmacokinetics and antimicrobial coverage. Results: There was no difference between the groups regarding dose, trough level or area under the curve. Coverage against gram-positive pathogens with a minimum inhibitory concentration of 1mg/L occurred in only 46% of patients in both groups. The pharmacokinetics in both groups were altered relative to the reference values, and the groups differed in regard to increased total body clearance and shortening of the biological half-life, which were more pronounced in younger patients. Conclusion: A minimum empirical dose of 60mg/kg per day should be prescribed for pediatric patients in intensive care units with preserved renal function. The use of the ratio between the area under the curve and minimum inhibitory concentration in the evaluation of vancomycin coverage is recommended to achieve the desired outcome, since the pharmacokinetics are altered in these patients, which may impact the effectiveness of the antimicrobial.

Synergistic antibacterial activity of monoterpenes in combination with conventional antimicrobials against Gram-positive and Gram-negative bacteria / Atividade antibacteriana sinérgica de monoterpenos combinados com antimicrobianos convencionais frente a bactérias Gram-positivas e Gram-negativas

Introduction: bacterial infections are a public health problem. Besides, the emergence of strains resistant to antimicrobials has contributed to the search for new alternatives, such for the terpenes with antimicrobial potential. Objectives: the objective of this study was to determine the possible interaction of isolated monoterpenes (-)-Carveol, Geraniol, Citronellol, α-terpineol, R-(-) Carvone, (-)-Menthol, Linalool, D-Dihydrocarvone, and (-)-Terpine-4-ol with conventional antimicrobials (Chloramphenicol, Minocycline, Amoxicillin and Ciprofloxacin) when they are evaluated on Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa strains. Methodology: the minimum inhibitory concentrations of these test drugs were determined using the microdilution method. The Checkerboard method was used to assess the interactions, by determining the fractional inhibitory concentration index (FIC index). Results: aamong the monoterpenes, only Carveol, Citronellol, and Geraniol presented antimicrobial activity (MIC < 1024 µg/mL). They presented synergistic effects against Pseudomonas aeruginosa ATCC-9027 (FIC index ≤ 0.5) when in combination with Minocycline. Conclusion: this study contributes to the development of new approaches to control bacterial resistance and to the possibility of discovering new drugs.

Introdução: as infecções bacterianas são um problema de saúde pública. Além disso, o surgimento de cepas resistentes aos antimicrobianos tem contribuído para a busca de novas alternativas, como a pesquisa de terpenos com potencial antimicrobiano. Objetivos: o objetivo deste estudo foi determinar a possível interação de monoterpenos isolados (-) - Carveol, Geraniol, Citronelol, α-terpineol, R - (-) Carvona, (-)-Mentol, Linalol, D-Diidrocarvona e (-)-Terpina-4-ol com antimicrobianos convencionais (cloranfenicol, minociclina, amoxicilina e ciprofloxacina) quando avaliados em Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, Escherichia coli e Pseudomonas aeruginosa. Metodologia: as concentrações inibitórias mínimas destas drogas foram determinadas usando o método de microdiluição. O método checkerboard foi utilizado para avaliar as interações, determinando o índice de concentração inibitória fracionária (índice FIC). Resultados: entre os monoterpenos, apenas Carveol, Citronelol e Geraniol apresentaram atividade antimicrobiana (CIM < 1024 µg/mL). Eles apresentaram efeitos sinérgicos contra Pseudomonas aeruginosa ATCC-9027 (índice FIC ≤ 0,5) quando em combinação com Minociclina. Conclusão: este estudo contribui para o desenvolvimento de novas abordagens para o controle da resistência bacteriana e para a possibilidade de descoberta de novas drogas.