Antimicrobial prescription and bacterial resistance in a Brazilian Intensive Care Unit / Prescrição antimicrobiana e resistência bacteriana em uma Unidade de Terapia Intensiva Brasileira / Prescripción antimicrobiana y resistencia bacteriana en una Unidad de Cuidados Intensivos Brasileña

Background and Objectives: antimicrobial resistance is one of the main public health concerns worldwide. Intensive Care Units have a high prevalence of resistant microorganisms and infections, and the rational use of antibiotics is one of the main strategies for tackling this problem. This work aimed to describe patterns associated with antimicrobial drugs as well as the resistance profile of microorganisms. Methods: an observational study was carried out using data from patients hospitalized in the Intensive Care Unit who used antimicrobial agents. Results: respiratory and cardiological causes were the most frequent reasons for admission, with cephalosporins (29.02%), with penicillin (25.84%) and macrolides (16.10%) being the most used classes of antibiotics. The predominant microorganisms were Klebsiella pneumoniae (13.98%), Staphylococcus aureus (13.44%) and Acinetobacter baumannii (11.83%). Urine cultures and tracheal aspirate were the culture tests with the highest growth of gram-negative microorganisms. Patients with bacteria isolated in tracheal aspirate had longer hospital stays; 20 patients had positive surveillance cultures; and the mortality rate found was 55.45%. Conclusion: the study combined the institution's epidemiological profile with patient characteristics, isolated microorganisms and outcomes.(AU)

Justificativa e Objetivos: a resistência antimicrobiana é uma das principais preocupações de saúde pública em todo o mundo. As Unidades de Terapia Intensiva têm uma alta prevalência de microorganismos resistentes e infecções, e o uso racional de antibióticos é uma das principais estratégias para lidar com esse problema. Este trabalho teve como objetivo descrever padrões associados a medicamentos antimicrobianos, bem como o perfil de resistência dos microorganismos. Métodos: foi realizado um estudo observacional utilizando dados de pacientes hospitalizados na Unidade de Terapia Intensiva que utilizaram agentes antimicrobianos. Resultados: causas respiratórias e cardiológicas foram os motivos mais frequentes de admissão, com cefalosporinas (29,02%), penicilina (25,84%) e macrolídeos (16,10%) sendo as classes de antibióticos mais utilizadas. Os microorganismos predominantes foram Klebsiella pneumoniae (13,98%), Staphylococcus aureus (13,44%) e Acinetobacter baumannii (11,83%). Culturas de urina e aspirado traqueal foram os testes de cultura com maior crescimento de microorganismos gram-negativos. Pacientes com bactérias isoladas no aspirado traqueal tiveram internações mais longas; 20 pacientes tiveram culturas de vigilância positivas; e a taxa de mortalidade encontrada foi de 55,45%. Conclusão: o estudo combinou o perfil epidemiológico da instituição com características dos pacientes, microorganismos isolados e resultados.(AU)

Antecedentes y Objetivos: la resistencia antimicrobiana es una de las principales preocupaciones de salud pública en todo el mundo. Las Unidades de Cuidados Intensivos tienen una alta prevalencia de microorganismos resistentes e infecciones, y el uso racional de antibióticos es una de las principales estrategias para abordar este problema. Este trabajo tuvo como objetivo describir patrones asociados con medicamentos antimicrobianos, así como el perfil de resistencia de los microorganismos. Métodos: se llevó a cabo un estudio observacional utilizando datos de pacientes hospitalizados en la Unidad de Cuidados Intensivos que utilizaron agentes antimicrobianos. Resultados: las causas respiratorias y cardiológicas fueron las razones más frecuentes de admisión, con cefalosporinas (29,02%), penicilina (25,84%) y macrólidos (16,10%) siendo las clases de antibióticos más utilizadas. Los microorganismos predominantes fueron Klebsiella pneumoniae (13,98%), Staphylococcus aureus (13,44%) y Acinetobacter baumannii (11,83%). Los cultivos de orina y el aspirado traqueal fueron las pruebas de cultivo con mayor crecimiento de microorganismos gramnegativos. Los pacientes con bacterias aisladas en el aspirado traqueal tuvieron estancias hospitalarias más largas; 20 pacientes tuvieron cultivos de vigilancia positivos; y la tasa de mortalidad encontrada fue del 55,45%. Conclusión: el estudio combinó el perfil epidemiológico de la institución con las características de los pacientes, los microorganismos aislados y los resultados.(AU)

Anti-Trichomonas vaginalis activity of ursolic acid derivative: a promising alternative.

Trichomonas vaginalis is an extracellular parasite that binds to the epithelium of the human urogenital tract and causes the sexually transmitted infection, trichomoniasis. In view of increased resistance to drugs belonging to the 5-nitroimidazole class, new treatment alternatives are urgently needed. In this study, eight semisynthetized triterpene derivatives were evaluated for in vitro anti-T. vaginalis activity. Ursolic acid and its derivative, 3-oxime-urs-12-en-28-oic-ursolic acid (9), presented the best anti-T. vaginalis activity when compared to other derivatives, with minimum inhibitory concentration (MIC) at 25 µM. Moreover, 9 was active against several T. vaginalis fresh clinical isolates. Hemolysis assay demonstrated that 9 presented a low hemolytic effect. Importantly, 25 µM 9 was not cytotoxic against the Vero cell lineage. Finally, we demonstrated that compound 9 acts synergistically with metronidazole against a T. vaginalis metronidazole-resistant isolate. This report reveals the high potential of the triterpenoid derivative 9 as trichomonicidal agent.

Adenosine, but not guanosine, protects vaginal epithelial cells from Trichomonas vaginalis cytotoxicity.

Trichomonas vaginalis causes the most common non-viral sexually transmitted disease worldwide. The cytoadherence and cytotoxicity upon the vaginal epithelial cells are crucial for the infection. Extracellular nucleotides are released during cell damage and, along with their nucleosides, can activate purinoceptors. The opposing effects of nucleotides versus nucleosides are regulated by ectonucleotidases. Herein we evaluated the hemolysis and cytolysis induced by T. vaginalis, as well as the extracellular nucleotide hydrolysis along with the effects mediated by nucleotides and nucleosides on cytotoxicity. In addition, the gene expression of purinoceptors in host cells was determined. The hemolysis and cytolysis exerted by all T. vaginalis isolates presented positive Pearson correlation. All T. vaginalis isolates were able to hydrolyze nucleotides, showing higher NTPDase than ecto-5'-nucleotidase activity. The most cytotoxic isolate, TV-LACM6, hydrolyzes ATP, GTP with more efficiency than AMP and GMP. The vaginal epithelial cell line (HMVII) expressed the genes for all subtypes of P1, P2X and P2Y receptors. Finally, when nucleotides and nucleosides were tested, the cytotoxic effect elicited by TV-LACM6 was increased with nucleotides. In contrast, the cytotoxicity was reversed by adenosine in presence of EHNA, but not by guanosine, contributing to the understanding of the purinergic signaling role on T. vaginalis cytotoxicity.

Five putative nucleoside triphosphate diphosphohydrolase genes are expressed in Trichomonas vaginalis.

Trichomonas vaginalis is a protozoan that parasitizes the human urogenital tract causing trichomoniasis, the most common non-viral sexually transmitted disease. The parasite has unique genomic characteristics such as a large genome size and expanded gene families. Ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) is an enzyme responsible for hydrolyzing nucleoside tri- and diphosphates and has already been biochemically characterized in T. vaginalis. Considering the important role of this enzyme in the production of extracellular adenosine for parasite uptake, we evaluated the gene expression of five putative NTPDases in T. vaginalis. We showed that all five putative TvNTPDase genes (TvNTPDase1-5) were expressed by both fresh clinical and long-term grown isolates. The amino acid alignment predicted the presence of the five crucial apyrase conserved regions, transmembrane domains, signal peptides, phosphorylation and catalytic sites. Moreover, a phylogenetic analysis showed that TvNTPDase sequences make up a clade with NTPDases intracellularly located. Biochemical NTPDase activity (ATP and ADP hydrolysis) is responsive to the serum-restrictive conditions and the gene expression of TvNTPDases was mostly increased, mainly TvNTPDase2 and TvNTPDase4, although there was not a clear pattern of expression among them. In summary, the present report demonstrates the gene expression patterns of predicted NTPDases in T. vaginalis.