RESUMO
Sepsis is the main cause of death in major burns. In this retrospective study conducted in a reference hospital in Brazil, the main agents causing infection and the resistance profile to antibiotics were identified. In addition, the epidemiological profile, length of hospital stay, type of burn, and total body surface area (TBSA) in major burns were collected from medical records, comparing the years 2015/2016 and 2019/2020. In both time periods, there was a predominance of males with a mean age of 43 years. Burns with less than 30% of TBSA predominated. There was a significant increase in positive cultures (P = .00026), from 58.7% to 80%, and an increase in skin punch culture collection from 25.6% to 43.9% in the years 2019/2020. The predominant etiological agent was Pseudomonas aeruginosa, followed by Acinetobacter baumannii resistant to carbapenems, and Staphylococcus aureus in both evaluated periods. The percentage of deaths was higher in 2019/2020 (26.2% vs. 14.6%; P = .026). The length of hospital stay was shorter in the latter period (P = .0081). Sepsis was the cause of death in 81.2% of cases in 2015/2020 and 78.3% in 2019/2020. Among the deaths, P. aeruginosa was the main agent identified. There was no change in the main pathogens and bacterial antibiotic resistance between the 2 time periods.
Assuntos
Queimaduras , Sepse , Masculino , Humanos , Adulto , Feminino , Estudos Retrospectivos , Brasil/epidemiologia , Testes de Sensibilidade Microbiana , Queimaduras/tratamento farmacológico , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Pseudomonas aeruginosa , Sepse/tratamento farmacológicoRESUMO
Background and objectives: inanimate surfaces and equipment in the hospital environment are considered reservoirs of resistant and pathogenic microorganisms. In Pediatric Intensive Care Units, the risk of infection is also related to the severity of pathologies associated with the immaturity of the immune system of this population. This study aimed to investigate microbiological environmental contamination in a Pediatric Intensive Care Unit. Method: this is an exploratory cross-sectional study, carried out in a Pediatric Intensive Care Unit of a highly complex university hospital, located in southern Brazil. To assess environmental contamination, sterile swabs were rubbed on surfaces corresponding to the patient unit and in the common area. Results: twenty-eight surfaces were analyzed, 12 of which were located in units occupied by patients at the time of collection and 16 surfaces in the common use area. In the total number of surfaces analyzed by microbiological cultures, the patient unit showed 66.67% contamination by microorganisms, while surfaces in the common area showed 56.25%. Regarding the microbiological profile, all isolated microorganisms were Gram-positive and showed resistance, namely Staphylococcus aureus and coagulase-negative Staphylococcus. Conclusion: there was evidence of a high frequency of contamination on inanimate surfaces and equipment near and far from patients, essentially by pathogenic and multi-resistant microorganisms to antimicrobials.(AU)
Justificativa e objetivos: superfícies e equipamentos inanimados no ambiente hospitalar são considerados reservatórios de microrganismos resistentes e patogênicos. Nas Unidades de Cuidados Intensivos Pediátricos, o risco de infeção também está relacionado com a gravidade das patologias associadas à imaturidade do sistema imunitário desta população. Este estudo teve como objetivo investigar a contaminação microbiológica ambiental em uma Unidade de Terapia Intensiva Pediátrica. Método: trata-se de um estudo exploratório transversal, realizado em uma Unidade de Terapia Intensiva Pediátrica de um hospital universitário de alta complexidade, localizado no Sul do Brasil. Para avaliar a contaminação ambiental, foram esfregados swabs estéreis nas superfícies correspondentes à unidade do paciente e na área comum. Resultados: foram analisadas vinte e oito superfícies, sendo 12 localizadas em unidades ocupadas por pacientes no momento da coleta e 16 superfícies em área de uso comum. No total de superfícies analisadas por culturas microbiológicas, a unidade paciente apresentou 66,67% de contaminação por microrganismos, enquanto as superfícies da área comum apresentaram 56,25%. Quanto ao perfil microbiológico, todos os microrganismos isolados eram Gram-positivos e apresentavam resistência, nomeadamente Staphylococcus aureus e Staphylococcus coagulase-negativa. Conclusão: houve evidência de elevada frequência de contaminação em superfícies inanimadas e equipamentos próximos e distantes dos pacientes, essencialmente por microrganismos patogênicos e multirresistentes aos antimicrobianos.(AU)
Fundamento y objetivos: las superficies y equipos inanimados del ambiente hospitalario son considerados reservorios de microorganismos resistentes y patógenos. En las Unidades de Cuidados Intensivos Pediátricos el riesgo de infección también se relaciona con la gravedad de patologías asociadas a la inmadurez del sistema inmunológico de esta población. Este estudio tuvo como objetivo investigar la contaminación ambiental microbiológica en una Unidad de Cuidados Intensivos Pediátricos. Método: se trata de un estudio exploratorio transversal, realizado en una Unidad de Cuidados Intensivos Pediátricos de un hospital universitario de alta complejidad, ubicado en el sur de Brasil. Para evaluar la contaminación ambiental se frotaron hisopos estériles en las superficies correspondientes a la unidad de pacientes y en el área común. Resultados: se analizaron veintiocho superficies, 12 de las cuales estaban ubicadas en unidades ocupadas por los pacientes en el momento de la recogida y 16 superficies en el área de uso común. Del total de superficies analizadas por cultivos microbiológicos, la unidad de pacientes presentó un 66,67% de contaminación por microorganismos, mientras que las superficies del área común presentaron un 56,25%. En cuanto al perfil microbiológico, todos los microorganismos aislados fueron Gram positivos y presentaron resistencia, concretamente Staphylococcus aureus y Staphylococcus coagulasa negativo. Conclusión: se evidenció alta frecuencia de contaminación en superficies inanimadas y equipos cercanos y lejanos de los pacientes, esencialmente por microorganismos patógenos y multirresistentes a los antimicrobianos.(AU)
Assuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Unidades de Terapia Intensiva Pediátrica , Infecção Hospitalar , Contaminação de Equipamentos , Estudos Transversais , Farmacorresistência Bacteriana MúltiplaRESUMO
As infecções do trato urinário causadas por bactérias resistentes aos antimicrobiano são o terceiro tipo de infecção mais comum em humanos, descritas em todo o mundo. Trata-se de estudo de série temporal realizado a partir de registros de urocultura positiva, no período de 1º de janeiro de 2011 a 31 de dezembro de 2019, na região metropolitana do município de Goiânia, Centro-Oeste do Brasil, em pessoas de todas as idades e sexos, com objetivo de avaliar a prevalência as infeções urinárias, o padrão de resistência aos antimicrobianos e a tendência do crescimento da resistência em Enterococcus faecalis. A análise descritiva e o teste Qui-quadrado de Pearson foram utilizados para avaliar o crescimento da prevalência da resistência aos antimicrobianos e a análise de correlação pelo método de Poisson foi usada para avaliar a tendência do crescimento da resistência bacteriana. De 22.034 registros de uroculturas positivas, 646 (2,9%) eram E. faecalis. Os achados demonstraram que as infeções urinárias são mais prevalentes em mulheres com idade superior a 19 anos. A prevalência da resistência foi elevada para as fluoroquinolonas e significante crescimento da resistência para Gentamicina (p=0,02%) e diminuição para Ampicilina (p<0,001) e Tobramicina (p<0,001). A tendência de crescimento positiva foi significante para a Gentamicina e negativa para Ampicilina e Tobramicina. Os achados demonstram que é necessária a criação de programas de vigilância que objetivam monitorar o crescimento do padrão de resistência nas ITUs comunitárias, levando em consideração o local de estudo.
Urinary tract infections caused by antibiotic-resistant bacteria are the third most common type of infection in humans described worldwide. This is a time series study carried out from positive urine culture records, from January 1, 2011, to December 31, 2019, in the metropolitan region of the municipality of Goiania, Midwest Brazil, in people of all ages and sexes. The aim was to assess the prevalence of urinary tract infections, the pattern of resistance to antibiotics, and the trend of increasing resistance in Enterococcus faecalis. Descriptive analysis and Pearson's chi-square test were used to assess the growth in the prevalence of antibiotic resistance, and a correlation analysis by the Poisson method was used to assess the trend in the growth of bacterial resistance. Of 22,034 positive urine cultures, 646 (2.9%) were of E. faecalis. The findings showed that urinary tract infections are more prevalent in women aged over 19 years old. The prevalence of resistance was high for the fluoroquinolone drugs and a significant increase in resistance against Gentamicin (p=0.02%) and a decrease toward Ampicillin (p<0.001) and Tobramycin (p<0.001). The increasing trend was significant for Gentamicin and negative for Ampicillin and Tobramycin. The findings demonstrate that it is necessary to create surveillance programs that aim to monitor the growth of the resistance patterns in public UTIs, while considering the study site.
RESUMO
Antiepileptic drugs have been successfully treating epilepsy and providing individuals sustained seizure freedom. However, about 30% of the patients with epilepsy present drug resistance, which means they are not responsive to the pharmacological treatment. Considering this, it becomes extremely relevant to pursue alternative therapeutic approaches, in order to provide appropriate treatment for those patients and also improve their quality of life. In the light of that, this review aims to discuss some innovative options for the treatment of epilepsy, which are currently under investigation, addressing strategies that go from therapeutic compounds to clinical procedures. For instance, peptides derived from animal venoms, such as wasps, spiders, and scorpions, demonstrate to be promising antiepileptic molecules, acting on a variety of targets. Other options are cannabinoids and compounds that modulate the endocannabinoid system, since it is now known that this network is involved in the pathophysiology of epilepsy. Furthermore, neurostimulation is another strategy, being an alternative clinical procedure for drug-resistant patients who are not eligible for palliative surgeries.
Assuntos
Canabinoides , Epilepsia , Animais , Anticonvulsivantes/uso terapêutico , Canabinoides/farmacologia , Canabinoides/uso terapêutico , Endocanabinoides , Epilepsia/tratamento farmacológico , Peptídeos , Qualidade de Vida , Peçonhas/uso terapêuticoRESUMO
Synaptic vesicle protein 2A (SV2A), the target of the antiepileptic drug levetiracetam (LEV), is expressed ubiquitously in all synaptic terminals. Its levels decrease in patients and animal models of epilepsy. Thus, changes in SV2A expression could be a critical factor in the response to LEV. Epilepsy is characterized by an imbalance between excitation and inhibition, hence SV2A levels in particular terminals could also influence the LEV response. SV2A expression was analyzed in the epileptic hippocampus of rats which responded or not to LEV, to clarify if changes in SV2A alone or together with glutamatergic or GABAergic markers may predict LEV resistance. Wistar rats were administered saline (control) or pilocarpine to induce epilepsy. These groups were subdivided into untreated or LEV-treated groups. All epileptic rats were video-monitored to assess their number of seizures. Epileptic rats with an important seizure reduction (>50%) were classified as responders. SV2A, vesicular γ-aminobutyric acid transporter and vesicular glutamate transporter (VGLUT) expression were assessed by immunostaining. SV2A expression was not modified during epilepsy. However, responders showed ≈55% SV2A-VGLUT co-expression in comparison with the non-responder group (≈40%). Thus, SV2A expression in glutamatergic terminals may be important for the response to LEV treatment.
RESUMO
Resumen Varón de 33 años con antecedentes de convulsiones febriles y discapacidad intelectual moderada grave, inició a los 2 años convulsiones tanto focales como generalizadas atónicas diarias, que ocasionaron traumas faciales. Debido a la farmacorresistencia se implantó un estimulador del nervio vago, con respuesta parcial al mismo. Durante su seguimiento, se hizo diagnóstico de enfermedad celíaca. Al realizar una tomografía de encéfalo se evidenciaron calcificaciones piriformes occipitales bilaterales, estableciéndose el diagnostico de enfermedad celiaca, epilepsia y calcificaciones cerebrales. Se le indicó dieta libre de gluten y continuar el tratamiento farmacológico, logrando de esta manera una reducción de las crisis.
Abstract A 33-year-old man with a history of febrile seizures and moderate-severe intellectual disability began, at 2 years, both focal and generalized daily atonic seizures, which caused facial trauma. Due to drug resistance, a vagus nerve stimulator was implanted, with partial response to it. During his follow-up, he was diagnosed with celiac disease. When performing a brain tomography, bilateral occipital pyriform calcifications were evidenced, establishing the diagnosis of celiac disease, epilepsy and cerebral calcifications. A gluten-free diet was indicated and pharmacological treatment continued, thus achieving a reduction in seizures.
Assuntos
Humanos , Masculino , Adulto , Encefalopatias , Calcinose/diagnóstico por imagem , Doença Celíaca/complicações , Epilepsia , EletroencefalografiaRESUMO
A 33-year-old man with a history of febrile seizures and moderate-severe intellectual disability began, at 2 years, both focal and generalized daily atonic seizures, which caused facial trauma. Due to drug resistance, a vagus nerve stimulator was implanted, with partial response to it. During his follow-up, he was diagnosed with celiac disease. When performing a brain tomography, bilateral occipital pyriform calcifications were evidenced, establishing the diagnosis of celiac disease, epilepsy and cerebral calcifications. A gluten-free diet was indicated and pharmacological treatment continued, thus achieving a reduction in seizures.
Varón de 33 años con antecedentes de convulsiones febriles y discapacidad intelectual moderada grave, inició a los 2 años convulsiones tanto focales como generalizadas atónicas diarias, que ocasionaron traumas faciales. Debido a la farmacorresistencia se implantó un estimulador del nervio vago, con respuesta parcial al mismo. Durante su seguimiento, se hizo diagnóstico de enfermedad celíaca. Al realizar una tomografía de encéfalo se evidenciaron calcificaciones piriformes occipitales bilaterales, estableciéndose el diagnostico de enfermedad celiaca, epilepsia y calcificaciones cerebrales. Se le indicó dieta libre de gluten y continuar el tratamiento farmacológico, logrando de esta manera una reducción de las crisis.
Assuntos
Encefalopatias , Calcinose , Doença Celíaca , Epilepsia , Adulto , Calcinose/diagnóstico por imagem , Doença Celíaca/complicações , Eletroencefalografia , Humanos , MasculinoRESUMO
Mesial temporal lobe epilepsy (mTLE) is the most common epilepsy syndrome which will eventually become pharmacologically intractable partial-onset seizures. Regulation of gene expression is an important process in the development of this pathology where microRNAs (miRs) are involved. The role of miRs has been widely studied in the hippocampus of rodents and patients. However, little is known about its differential expression in other brain regions such as the neocortex. The temporal neocortex plays a major role in the generation and propagation of seizures and in synaptic disruption, impairing the excitatory and inhibitory balance. Therefore, we assessed the expression of miR-146a, 34a, 1260, 1275, 1298, 451, 132 and 142-3p in the neocortex of 12 patients with mTLE and compared them with miRs expression found in 10 control samples. We noted a significant decrease in the expression of miR-34a and 1298 in patients with mTLE and a -1.49 to -7.0 fold change respectively compared with controls. Conversely, we observed a significant increase in the expression of miR-451, 1260 and 1275 in patients with a 25.67, 4.09 and a 7.07 fold change respectively compared to controls. Using Pearson correlation, we explored the association between the clinical features of mTLE patients and controls with miRs expression. In the control group we found a significant correlation only with age and miR-146a expression (râ¯=â¯0.733). The analysis of mTLE patients showed a negative correlation between expression of miR-1260 (râ¯=â¯-0.666) and miR-1298 (râ¯=â¯-0.651) and age. Furthermore, we found a positive correlation between miR-146a expression with seizure frequency (râ¯=â¯0.803) and a positive correlation between miR-146a and 451 expression with number of antiepileptic drugs used for presurgical treatment (râ¯=â¯0.715 and 0.611 respectively), thus suggesting a positive correlation with disease severity. These miRs are associated with biological processes such as apoptosis, drug resistance, inflammation, inhibitory and excitatory synaptic transmission, axonal guidance and signaling of neurotrophins. Therefore, deepening our understanding of the targets involved in these miRs will help to elucidate the role of the neocortex in epilepsy.
Assuntos
Epilepsia do Lobo Temporal/metabolismo , MicroRNAs/metabolismo , Neocórtex/metabolismo , Adolescente , Adulto , Feminino , Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Adulto JovemRESUMO
The vascular endothelial growth factor (VEGF) system has been shown to play a crucial role in several neuropathological processes. Temporal lobe epilepsy (TLE) is the most common focal epilepsy type in adult humans. We assessed the protein expression levels of VEGF-A, VEGF-B, and VEGF-C, their specific receptors VEGFR-2 and -3, their accessory receptors neuropilins 1 and 2, and PI3 and Akt kinases, in temporal neocortex from pharmacoresistant TLE (PR-TLE) patients and control subjects by western blotting. All proteins were found to be significantly overexpressed in samples of PR-TLE patients, indicating that the VEGF system contributes to PR-TLE pathogenesis and should be further studied.
Assuntos
Epilepsia Resistente a Medicamentos/metabolismo , Epilepsia do Lobo Temporal/metabolismo , Neocórtex/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossíntese , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
RESUMEN Introducción: la práctica de la Medicina enfrenta frecuentemente al manejo de pacientes del sexo femenino con infección de vías urinarias no complicada, en las que se necesita iniciar un tratamiento empírico para Escherichia coli, basado en la identificación de los llamados antibióticos de primera línea para dicho germen y en el conocimiento de la resistencia local a los mismos. Objetivos: analizar los textos de Medicina Interna, Nefrología, Microbiología, guías internacionales y otras publicaciones recientes para identificar los antibióticos como los de primera línea para el tratamiento de la cistitis aguda no complicada en la mujer: nitrofurantoína, fosfomicina, cotrimoxazol (trimetoprim-sulfametoxazol) y pivmecillinam. Resultados: de los antibióticos mencionados sólo están disponibles en el país la nitrofurantoína y el cotrimoxazol. En un estudio que hemos publicado recientemente se encontró que la resistencia de Escherichia coli a la nitrofurantoína fue 4% y al cotrimoxazol fue del 35%. Conclusión: de los antibióticos considerados de primera línea para el tratamiento empírico de la cistitis aguda no complicada en la mujer, solo tenemos disponible en el país la nitrofurantoína y el cotrimoxazol, siendo baja (4%) la resistencia local de Escherichia coli a la nitrofurantoina y elevada (35%) al cotrimoxazol.
ABSTRACT Introduction: The practice of medicine frequently faces the management of female patients with uncomplicated urinary tract infection, in which an empirical treatment for Escherichia coli is needed, based on the identification of the so-called first-line antibiotics for this germ and in the knowledge of local resistance to them. Objectives: To analyze the texts of Internal Medicine, Nephrology, Microbiology, international guidelines and other recent publications to identify the following antibiotics as those of first line for the treatment of uncomplicated acute cystitis in women: nitrofurantoin, fosfomycin, cotrimoxazole (trimethoprim -sulfamethoxazole) and pivmecillinam. Results: Of the above mentioned antibiotics, only nitrofurantoin and cotrimoxazole are available in Paraguay. In a study we recently published it was found that the resistance of E. coli to nitrofurantoin was 4% and to cotrimoxazole 35%. Conclusion: Of the antibiotics considered as of first line for the empirical treatment of uncomplicated acute cystitis in women, only nitrofurantoin and cotrimoxazole are available in the country, being low (4%) the local resistance of E. coli to nitrofurantoin and high (35%) to cotrimoxazole.
RESUMO
The efficiency of most of the new antiepileptic drugs (AEDs) on clinical trials still falls short the success reported in pre-clinical studies, possibly because the validity of the animal models is insufficient to fully represent the human pathology. To improve the translational value for testing AEDs, we propose the use of non-human primates. Here, we suggest that triggering limbic seizures with low doses of PTZ in pilocarpine-treated marmosets might provide a more effective basis for the development of AED. Marmosets with epileptic background were more susceptible to seizures induced by PTZ, which were at least 3 times longer and more severe (about 6 times greater frequency of generalized seizures) in comparison to naïve peers. Accordingly, PTZ-induced seizures were remarkably less attenuated by AEDs in epileptic than naïve marmosets. While phenobarbital (40mg/kg) virtually abolished seizures regardless of the animal's background, carbamazepine (120mg/kg) and valproic acid (400mg/kg) could not prevent PTZ-induced seizures in epileptic animals with the same efficiency as observed in naïve peers. VPA was less effective regarding the duration of individual seizures in epileptic animals, as assessed in ECoG (p=0.05). Similarly following CBZ treatment, the behavioral manifestation of generalized seizures lasted longer in epileptic (p<0.05), which were also more frequent than in the naïve group (p<0.05). As expected, epileptic marmosets experiencing stronger seizures showed more NPY- and ΔFosB-immunostained neurons in a number of brain areas associated with the generation and spread of limbic seizures. Our results suggest that PTZ induced seizures over an already existing epileptic background constitutes a reliable and controllable mean for the screening of new AEDs.
Assuntos
Anticonvulsivantes/farmacologia , Modelos Animais de Doenças , Epilepsia/tratamento farmacológico , Convulsões/tratamento farmacológico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/fisiopatologia , Callithrix , Carbamazepina/farmacologia , Doença Crônica , Eletrocorticografia , Epilepsia/induzido quimicamente , Epilepsia/patologia , Epilepsia/fisiopatologia , Feminino , Imuno-Histoquímica , Masculino , Neuropeptídeo Y/metabolismo , Pentilenotetrazol , Fenobarbital/farmacologia , Pilocarpina , Proteínas Proto-Oncogênicas c-fos/metabolismo , Convulsões/induzido quimicamente , Convulsões/patologia , Convulsões/fisiopatologia , Ácido Valproico/farmacologiaRESUMO
A otite resulta de qualquer inflamação do conduto auditivo, com numerosos agentes etiológicos envolvidos e diferentes fatores predisponentes, figurando dentre as infecções mais frequentes em cães, em qualquer faixa etária. Objetivou-se nesse estudo, identificar e comparar a frequência de agentes etiológicos da otite em cães domiciliados e errantes, bem como avaliar a susceptibilidade a antimicrobianos utilizados na clínica veterinária. As colheitas foram realizadas no município de Viçosa, Alagoas, com o auxílio de swabs esterelizados, na região média dos dois ouvidos de cada animal, sendo 10 cães errantes e 10 cães domiciliados, totalizando 40 amostras, as quais foram submetidas a exame direto e microbiológico. As bactérias isoladas foram submetidas ao teste de sensibilidade microbiana in vitro, utilizando o método de difusão com discos antimicrobianos de: Cefalexina (30ug), Eritromicina (15ug), Tobramicina (10ug), Azitromicina (15ug) e Sulfazotrin (25ug). No exame microbiológico foram identificados Staphylococcus sp., Streptococcus sp., Bacillus sp. e Malassezia sp., e a frequência de animais domiciliados positivos neste mesmo exame foi de 50% (5/10), enquanto nos errantes foi de 70% (7/10). A incidência de agentes patogênicos da otite em cães errantes supera a de cães domiciliados por estes estarem sujeitos a várias en- fermidades e supressões do sistema imunológico, que são fatores primários para a otite. Nos cães domiciliados, 60% (3/5) apresentaram agentes, sendo estes Staphylococcus sp. e Bacillus sp., resistentes a todos os antimicrobianos, tendo os outros 40% (2/5) Sta- phylococcus sp.com susceptibilidade intermediária somente ao Cefalexina. Já nos cães errantes, 85,72% (6/7) apresentaram agentes, sendo estes Staphylococcus sp., Steptococcus sp. e Bacillus sp., resistentes a todos os antimicrobianos, enquanto 14,28% (1/7) também apresentaram Staphylococcus sp. com susceptibilidade intermediária somente a Cefalexina, sendo este antibiótico, portanto, o mais eficaz desse estudo. A maior frequência de bactérias resistentes em cães errantes pode ser justificada pelo fato destes se infectarem e as propagarem entre si, uma vez que os microrganismos resistentes podem passar os genes da resistência à sua descendência, onde as bactérias que transferem ou recebem estes genes podem ser até mesmo de gêneros diferentes. Nos animais do- miciliados a frequência de bactérias resistentes foi menor, porém, a multirresistência aos antibióticos evidencia a importância do controle do uso de antibióticos, bem como o uso de exames laboratoriais para a avaliação da susceptibilidade a antimicrobianos pelo médico veterinário, a fim de obter maior sucesso na cura e diminuir a seleção de microrganismos resistente.