Plano de ação nacional de prevenção e controle da resistência aos antimicrobianos no âmbito da saúde única: 2018-2022 / National Action Plan for the Prevention and Control of Antimicrobial Resistance in the One Health Framework: 2018-2022

No presente documento, é apresentado o Plano Estratégico do PAN-BR (formato executivo), que contém 14 Objetivos Principais, 33 Intervenções Estratégicas e 75 Atividades, alinhados aos 5 Objetivos Estratégicos do Plano de Ação Global.

Antimicrobial and antibiofilm activities of phenolic compounds extracted from Populus nigra and Populus alba buds (Algeria)

The interest of this work is the discovery of new antimicrobial agents of plant origin to inhibit the formation of microbial biofilms. The present research was conducted to identify and quantify the phenolic compounds extracted from Populus nigra and Populus alba buds harvested in the area of Tizi-Ouzou (Algeria), and to evaluate their antimicrobial and antibiofilm activity. High performance liquid chromatography (HPLC) was performed to identify the phenolic compounds in the ethyl acetate fraction of P. nigra and the methanolic extracts of P. nigra and P. alba. The antimicrobial activity of the crude extracts and the fractions of these two species was tested against 11 microorganisms, using the disk diffusion method, while the antibiofilm effect of certain extracts was carried out in a 96-well microplate and on a biomaterial (catheter). HPLC analysis revealed the presence of 10 bioactive compounds. The main phenolic compounds identified in the three extracts were p-coumaric acid, ellagic acid, and Kaempferol. This study was able to demonstrate that the extracts of P. nigra and P. alba buds have interesting antimicrobial properties, with diameters ranging from 6.6 to 21.3 mm. In addition, extracts of P. nigra exhibited antibiofilm effects greater than 70%. Our results provide evidence for the antimicrobial and antibiofilm potential of bud extracts from both poplar species. Thus, these results will pave the way for further research on these two plants.

Racionalização de antimicrobianos em ambiente hospitalar / Antimicrobial stewardship program in hospitals

Foi feita uma revisão sobre o uso racional de antimicrobianos em ambiente hospitalar, pois este é um dos principais desafios encontrados na terapia de infecções em ambiente hospitalar. Foram abordados os principais fatores que nos levam ao atual panorama global em relação à resistência antimicrobiana, bem como as principais estratégias para o uso racional dos antimicrobianos, de modo a garantir melhor terapêutica e menor incidência de resistência aos antimicrobianos. A racionalização de antimicrobianos é um componente-chave de uma abordagem multifacetada para a prevenção de resistência antimicrobiana. A boa gestão de antimicrobianos envolve a seleção do medicamento apropriado, otimizando sempre a dose e a duração do tratamento, utilizando bem os parâmetros de farmacodinâmica e farmacocinética, minimizando a toxicidade e as condições para a seleção de cepas bacterianas resistentes e garantindo, assim, sucesso terapêutico. Com o uso racional de antimicrobianos, podemos obter um melhor desempenho no tratamento de doenças infecciosas. Nesta revisão foi demonstrada a existência de várias estratégias de racionalização de antimicrobianos. Portanto, cabe a cada instituição estudar e analisar quais métodos devem ser implantados. Também é de fundamental importância que o prescritor analise as opções terapêuticas disponíveis e busque a individualização do tratamento, sempre visando à otimização terapêutica.(AU)

A review on antimicrobial stewardship was performed, because this is one of the leading challenges found in infectious diseases therapy in hospital settings. The major factors leading to the current global picture regarding antimicrobial resistance, and the main strategies for antimicrobial stewardship, to ensure the best treatment and lower incidence of antimicrobial resistance were discussed. Antimicrobial stewardship is a multifaceted approach considered a key component in the prevention of antimicrobial resistance. The best antimicrobial stewardship program involves selecting the appropriate medication, always optimizing its dose and duration of treatment using pharmacodynamics and pharmacokinetics parameters, minimizing toxicity and the conditions for selecting resistant bacterial strains, and ensuring treatment success. The rational use of antimicrobials can lead to more success in the treatment of infectious diseases. This review shows several strategies for antimicrobial stewardship. Therefore, it is up to each institution to study and analyze which method should be implemented. It is also crucial that the prescriber reviews the therapeutic options available to seek individualization of treatment, always aiming at therapy optimization.(AU)

The use of antimicrobials in septic patients with acute kidney injury / O uso de antimicrobianos em pacientes sépticos com lesão renal aguda

Abstract Sepsis is the most common cause of death in critically ill patients and it may be associated with multiorgan failure, including acute kidney injury (AKI). This situation can require acute renal support and increase mortality. Therefore, it is essential to administrate antimicrobials in dosis to achieve adequate serum levels, preventing overdosis and drug toxicity or underdosing and risk for resistance to antibiotics and higher mortality. To date, there aren't validated guidelines on antibiotic dosis adjustment in septic patients with AKI and the recommendations are extrapolated from studies conducted in non-critical patients with chronic kidney disease in end stage receiving chronic renal replacement therapy. This study aimed to review and discuss the complexity of that issue, considering the several factors related to the drugs removal: critically ill patient characteristics, antimicrobial properties and dialysis method.

Resumo A sepse é a principal causa de óbito em pacientes críticos e pode cursar com falência de vários órgãos, entre eles os rins, requerendo, com frequência, suporte renal agudo e elevando a mortalidade. Assim, torna-se imprescindível a administração de antimicrobianos em dose que garanta nível sérico adequado para evitar superdosagem e toxicidade medicamentosa ou ainda subdosagem e risco de resistência microbiana, ambas as situações contribuindo para maior mortalidade. Até o momento, não há diretrizes validadas para auxiliar no ajuste de dose de antibióticos nos pacientes sépticos com lesão renal aguda em suporte renal, sendo as recomendações extrapoladas de estudos realizados em pacientes não críticos e com doença renal em estádio final recebendo terapia renal substitutiva crônica. Esse estudo teve como objetivo revisar e discutir a complexidade desse assunto, levando em consideração os vários fatores relacionados à remoção de drogas: características do paciente crítico, propriedades dos antimicrobianos e método dialítico utilizado.

Prescripción de antimicrobianos y su relación con la resistencia bacteriana en un hospital general municipal / Antimicrobians prpescription and their relationship with the bacterial resistance in a municipal general hospital

Se realizó un estudio descriptivo y transversal, de utilización de medicamentos de tipo prescripción-indicación, de los 303 adultos que recibieron tratamiento antimicrobiano, ingresados en los servicios de Cuidados Intensivos, Medicina Interna y Cirugía del Hospital General Orlando Pantoja Tamayo del municipio de Contramaestre, desde enero hasta junio de 2015, con vistas a evaluar la prescripción de estos medicamentos y su relación con la resistencia bacteriana. En la serie, de un total de 568 prescripciones evaluadas predominaron las inadecuadas (82,3 por ciento); asimismo, los antimicrobianos más prescriptos resultaron ser la cefuroxima y la ceftriaxona, que también presentaron el mayor número de cepas resistentes y el Staphylococcus aureus resultó ser el germen con mayor resistencia

A descriptive and cross-sectional study on the use of prescription-indication medications of the 303 adults that received antimicrobian treatment was carried out. They were admitted to the Intensive Care, Internal Medicine and Surgery services of Orlando Pantoja Tamayo General Hospital in Contramaestre, from January to June, 2015, aimed at evaluating the prescription of these medications and their relationship with the bacterial resistance. In the series, there was a prevalence of inadequate prescriptions (82.3 percent) from a total of 568 that were evaluated; also, the most prescribed antimicrobians were the cefuroxime and the ceftriaxone that also presented the highest number of resistant stumps and the Staphylococcus aureus was the germ with higher resistance

Phytoconstituents from Sidastrum micranthum (A. St.-Hil.) Fryxell (Malvaceae) and antimicrobial activity of pheophytin a

abstract Sidastrum micranthum (A. St.-Hil.) Fryxell, a member of the Malvaceae family, is called malva preta in Brazil. As this species is commonly used to treat bronchitis, cough, and asthma, better knowledge of its chemical compounds is important. The phytochemical study of its hexane extract, using chromatographic techniques, led to isolation of six compounds: the triterpene isoarborinol, a mixture of sitosterol and stigmasterol, sitosterol-3-O-β-D-glucopyranoside, pheophytin a, and 132-hydroxy-(132-S)-pheophytin a. Structural identification of these compounds was carried out using spectroscopic methods such as IR and 1D and 2D NMR (HOMOCOSY, HMQC, HMBC, and NOESY). Compounds isolated from S. micranthum were screened for their in vitro antifungal and antibacterial activity against twenty fungal and bacterial standard strains. Pheophytin a exhibited antimicrobial action against all microorganisms tested.

resumo Sidastrum micranthum (A. St.-Hil.) Fryxell, pertencente à família Malvaceae, é conhecida no Brasil como "malva preta". A espécie é popularmente usada contra bronquite, tosse e asma, mostrando a relevância de conhecer melhor sua composição química. O estudo fitoquímico do extrato hexânico da espécie, utilizando técnicas cromatográficas, conduziu ao isolamento de seis compostos: o triterpeno isoarborinol, mistura de sitosterol e estigmasterol, sitosterol-3-O-β-D-glicopiranosídeo, feofitina a e de 132-hidroxi-(132-S)-feofitina a. A identificação estrutural destes compostos foi realizada com base em métodos espectroscópicos, tais como IV, RMN 1D e 2D (HOMOCOSY, HMQC, HMBC e NOESY). As substâncias isoladas de Sidastrum micranthum foram avaliadas quanto às suas atividades antimicrobianas in vitro, contra vinte cepas fúngicas e bacterianas. A feofitina a mostrou ação antimicrobiana contra todos os microrganismos testados.

Development and validation of a rapid turbidimetric assay to determine the potency of norfloxacin in tablets

Norfloxacin is one of the first commercially available (and most widely used) fluoroquinolone antibiotics. This paper reports the development and validation of a simple, sensitive, accurate and reproducible turbidimetric assay method to quantify norfloxacin in tablets formulations in only 4 hours. The bioassay is based on the inhibitory effect of norfloxacin upon the strain ofStaphylococcus epidermidis ATCC 12228 IAL 2150 used as test microorganism. The assay was performed 3x3 parallel lines like, three tubes for each concentration of reference substance and three tubes for each sample concentration. The results were treated statistically by analysis of variance and were found to be linear (r2 = 0.9999) in the selected range of 25-100 μg mL-1; precise (intra-assay: relative standard deviation (RSD) = 1.33%; inter-assay: RSD = 0.21%), accurate (100.74%) and robust with RSD lower than 4.5%. The student's t-test showed no statistically significant difference between the proposed turbidimetric method and an HPLC method previously validated. However the turbidimetric assay can be used as a valuable alternative methodology for the routine quality control of this medicine, complementary to other physical-chemical methods.

O norfloxacino foi a primeira fluorquinolona (e mais utilizada) disponível no mercado. Este trabalho divulga um novo desenvolvimento e validação de um método turbidimétrico simples, sensível, preciso e reprodutível para a quantificação de norfloxacino em comprimidos em apenas 4 horas. O bioensaio é baseado no efeito inibitório de norfloxacino sobre a cepa Staphylococcus epidermidis ATCC 12228 IAL 2150, utilizada como micro-organismo teste. O bioensaio foi efetuado através do delineamento de linhas paralelas 3x3, em que três tubos foram utilizados para a solução padrão e três tubos para as concentrações da amostra. Os resultados foram tratados estatisticamente pela análise de variância, apresentando coeficiente de correlação linear der2 = 0,9999, na faixa de 20 a 100 μg mL-1; precisão (intra-ensaio: desvio padrão relativo (RSD) 1,33%; inter-ensaio: RSD=0,21%), exatidão (100,74%) e robustez com RSD menor que 4,5%. O teste-tmostrou não haver diferença estatisticamente significativa entre o método turbidimétrico proposto e um método por HPLC previamente validado. No entanto, o ensaio turbidimétrico pode ser utilizado como método alternativo para o controle de qualidade de rotina para este antimicrobiano, como um complemento de outros métodos físico-químicos.

Tolerance Tests of Alcaligenes faecalis BW1 Extract.

Aims: To highlight whether metabolites of Alcaligenes faecalis BW1 extract can be administered orally for their possible antimycobacterial effects. Study Design: Study of the influence of certain parameters on the extract of Alcaligenes faecalis by using either discs or well diffusion methods against M. smegmatis. Place and duration of study: Laboratory of Microbial Biotechnology, Department of Biology, Faculty of Sciences and Technical, University Sidi Mohamed Ben Abdellah, BP 2202, Road of Immouzer, Fez, Morocco. From April to August, 2012. Methodology: The impact of acidic pH of gastric juice, bile, hydrogen peroxide, pancreatic enzymes and lysozyme on the antimycobacterial activity of Alcaligenes faecalis BW1 extract was evaluated by agar diffusion method. Detection whether or not antibacterial metabolites having a synergistic effect with rifampicin against M. smegmatis was also explored. Results: Antibacterial metabolites of Alcaligenes faecalis BW1 extract resist to the action of gastric pH, gallbladder bile and hydrogen peroxide. In addition, they are not affected by pancreatic enzymes and lysozyme. Moreover, they have a synergistic effect with rifampicin against M. smegmatis. Conclusion: Anti-mycobacterial metabolites of Alcaligenes faecalis BW1 extract are compatible with rifampicin and could be administered orally as antitubercular agents after their purification, identification in further work.

Assessment of ion diffusion from a calcium hydroxide-propolis paste through dentin

This study evaluated the ability of ions from a non-alcoholic calcium hydroxide-propolis paste to diffuse through dentinal tubules. Thirty-six single-rooted bovine teeth were used. The tooth crowns were removed, and the root canals were instrumented and divided into 3 groups: Group 1 - calcium hydroxide-propylene glycol paste; Group 2 - calcium hydroxide-saline solution paste; Group 3 - calcium hydroxide-propolis paste. After the root canal dressings were applied, the teeth were sealed and placed in containers with deionized water. The pH of the water was measured after 3, 24, 72 and 168 hours to determine the diffusion of calcium hydroxide ions through the dentinal tubules. All of the pastes studied promoted the diffusion of calcium hydroxide ions through the dentinal tubules. Associating propolis to calcium hydroxide resulted in a pH increase, which occurred with greater intensity after 72 hours. The calcium hydroxide-propolis paste was able to diffuse in dentin.

Pharmacokinetics, tissue residue and plasma protein binding of ofloxacin in goats

Ofloxacin was administered to six male goats intravenously (5 mg/kg) to determine its kinetic behavior, tissue residue, in vitro plasma protein binding and to compute a rational dosage regimen. The concentration of ofloxacin in plasma and tissue samples collected at prescheduled time were estimated by using HPLC. The pharmacokinetic parameters were determined by non-compartmental model and plasma protein binding was estimated by equilibrium dialysis technique. The therapeutic concentration (> or = 0.5 microgram/ml) was maintained up to 36 h and the initial concentration at 2.5min (14.76 +/- 0.47 microgram/ml) declined to 0.05 +/- 0.03 microgram/ml at 96 h with a secondary peak (0.64 +/- 0.15 microgram/ml) at 24 h. The mean AUC, AUMC, t1/2, MRT, Cl and Vd were calculated to be 58.94 +/- 19.43 microgram h/ml, 1539.57 +/- 724.69 microgram h2/ml, 15.58 +/- 1.87 h, 22.46 +/- 2.71 h, 135.60 +/- 31.12 ml/h/kg and 2.85 +/- 0.74 L/kg respectively. Significantly high concentration of drug was detected in different tissues after 24 h of intravenous dosing of 5mg/kg, at 24 h interval for 5 days. The in vitro plasma protein binding of ofloxacin was found to be 15.28 +/- 0.94%. Based on these kinetic parameters, a loading dose of 5mg/kg followed by the maintenance dose of 3mg/kg at 24 h dosing interval by intravenous route is recommended.

Pharmacokinetics of ciprofloxacin in patients with liver cirrhosis.

BACKGROUND: Bacterial infections are common in patients with cirrhosis of liver and are frequently treated with ciprofloxacin. Literature on pharmacokinetics of ciprofloxacin in patients with cirrhosis of the liver is scanty. The present study compared the pharmacokinetics of ciprofloxacin in cirrhotic patients with that in healthy volunteers. METHODS: In 20 patients with cirrhosis of liver (all Child-Pugh class B) and 10 healthy volunteers, plasma levels of ciprofloxacin were measured using high-performance liquid chromatography at several time points after a 500-mg oral dose. Various pharmacokinetic parameters were calculated. RESULTS: No significant differences were observed in maximum plasma levels reached (mean [SD] 2.6 [0.6] vs 2.6 [1.3] microg/ml), time taken for maximum plasma levels to be reached (1.3 [0.6] vs 1.5 [0.9] h), t1/2a (0.7 [0.3] vs 0.4 [0.9] h), elimination half-life (3.6 [1.2] vs 3.2 [1.8] h), and area under the curve (19.3 [3.8] vs 21.9 [4.5] microg/mL x h) in healthy volunteers and cirrhotic patients, respectively. CONCLUSIONS: Pharmacokinetics of ciprofloxacin is unaltered in patients with liver cirrhosis. Ciprofloxacin can be safely administered in the usual doses in such patients.

Consideraciones generales sobre el uso de agentes antimicrobianos en pacientes hepáticos / General remarks: antimicrobial agents use in hepatic patients

El hígado juega un papel fundamental en el metabolismo de las drogas, incluyendo los antimicrobianos. En los pacientes con enfermedad hepática, se deben monitorizar cuidadosamente los efectos adversos y toxicidad de estos medicamentos. En este artículo se analizan los aspectos del metabolismo de los antimicrobianos, particularmente relacionados a los cambios farmacocinéticos en los pacientes hepáticos. Además, se dan algunas recomendaciones prácticas sobre su uso en estos pacientes

Esparfloxacino e as fluorquinolonas: uma revisäo de sua classificaçäo, atividade antibacteriana, mecanismo de açäo, características farmacocinéticas, tolerabilidade e perspectivas farmacêuticas / Sparfloxacin and the fluoroquinolones: a review of classification, antibacterial activity, mechanism of action, pharmacokinetic properties, tolerability and pharmaceutical perspectives

Foi realizada uma revisäo na literatura sobre as quinolonas, classe antibacteriana que possui amplo espectro de açäo, enfocando, principalmente, o esparfloxacino, fluorquinolona de terceira geraçäo que possui potente atividade contra bactérias Gram-positivas, como Streptococcus pneumoniae e Staphylococcus aureus inclusive cepas metilina resistentes (MRSA), bactérias Gram-negativas, anaeróbios, Legionella spp, Mycoplasma spp, Chlamydia spp e Mycobacterium spp.

Quinolonas: revision historica / Quinolones: historic review

En las últimas tres décadas, se produjo el desarrollo farmacoterapéutico de las quinolonas. El primer producto, que se incorporó al comercio en el año 1965, fue el ácido nalidíxico (quinolona de primera generación) y luego, los químicos sintetizaron varios miles de derivados modificando primariamente la posición N-1y las posiciones C-6, C-7 y C-8 sobre el anillo quinolona-naftiridona. Los cambios estructurales incorporados en los nuevos compuestos aumentaron las propiedades farmacodinámicas y mejoraron los perfiles farmacocinéticos. Las quinolonas de tercera generación (levofloxacina, clinafloxacina, sparfloxacina, grepafloxacina, DU-6859a y trovafloxacina) presentan varias ventajas sobre las quinolonas de primera generación (ácido nalidíxico, cinoxacina y ácido oxolínico) y sobre las quinolonas de segunda generación (norfloxacina, enoxacina, ciprofloxacina, pefloxacina, ofloxacina, lomefloxacina y fleroxacina). Las nuevas fluoroquinolonas son bien absorbidas en el duodeno y el yeyuno, poseen grandes volúmenes de distribución y se ha demostrado en el hombre su penetración en diferentes tejidos y líquidos corporales, alcanzando concentraciones iguales o mayores que aquellas observdas en el plasma. Las quinolonas de tercera generación son antimicrobianos de amplio espectro, con elevada potencia in vitro en la actidad frente a las bacterias gram-positivas y gram-negativas, incluyendo anaerobios y patógenos intracelulares.

Farmacocinetica de la trovafloxacina: su significado clinico / Pharmacokinetics of trovafloxacin: its clinical significance

La trovafloxacina se absorbe rápidamente después de su administración oral y llega a su concentración sérica máxima alrededor de una hora. La alatrofloxacina es la prodroga que, al administrarse por vía endovenosa se hidrolisa rápidamente a su estado original. La biodisponibilidad es equivalente cuando se administra por vía oral o endovenosa. La trovafloxacina es una fluoroquinolona de amplio espectro in vitro, con mayor actividad para cocos positivos, anaerobios y para bacterias productoras de neumonías atípicas. Presenta una vida media cercana a las 11 horas y una mayor unión proteica, lo que permite su dosificación única diaria. La excreción renal es inferior al 8 por ciento y no requiere ajuste de dosis en la insuficiencia renal. La trovafloxacina alcanza mayores concentraciones tisulares e intracelulares que las fluoroquinolonas clásicas. Todas estas características farmacocinéticas y farmacodinámicas permiten considerarla como una droga de posible aplicación para el tratamiento de infecciones mixtas o resistentes a drogas de primera línea.

Indice inhibitorio (II) e índice bactericida (IB): parámetros que favorecen la comparación de la actividad de agentes antimicrobianos / Inhibitory index (II) and bactericidal index (BI): parameters that allow antimicrobial agents activity comparison

Se define el indice inhibitorio (11) como la relación entre la concentración plasmática máxima (CMáx) que alcanza un agente antibacteriano in vivo y su actividad inhibitorio ín vitro, expresada en forma de CIM. Al mismo tiempo, el indice bactericida (IB) se define como la relación entre la CMáx del antibacteriano y su concentración bactericida mínima CBM. Se estudió la actividad inhibitoria, bactericida y la correlación entre la CMáx y la actividad inhibitoria y bactericida de ciprofioxacina, temafloxacina y tosufloxacina sobre cepas de bacilos Gram negativos multiresistentes aislados de diferentes hospitales chilenos y se calcularon los 11 y los lB. Las quinolonas demostraron una elevada actividad inhibitoria y bactericida sobre E. coli y K. pneumoniae multiresistente, pero inferior sobre bacilos Gram negativos ' no fermentadores. Ciprofloxacina mostró mayor acción sobre P. aerugínosa y tosufloxacina sobre A. baumannií. En cambio la actividad inhibitoria y bactericida fue similar para ciprofioxacina y tosufloxacina e inferior para temafloxacina. Los 11 y IB demostraron que ciprofioxacina y temafloxacina tienen actividad comparable, mientras que tosufloxacina es menos eficiente. Estos índices, al relacionar la CMáx con las actividades inhibitoria y bactericida, surgen como interesantes parámetros de comparación entre agentes antimicrobianos, permitiendo obtener una aproximación más adecuada de su probable eficacia ín vivo