The potential of the antiplatelet agent ticagrelor as a new antibacterial agent

The number of deaths caused by drug-resistant bacteria is expected to increase in the future, and there is a need to develop new antimicrobial agents. Recently, the antiplatelet drug ticagrelor has been reported to have promising antibacterial properties. The purpose of this review is to analyze articles and case reports that describe the antimicrobial action of ticagrelor. Ticagrelor was found to have antibacterial reactions against Gram-positive bacteria, including drug-resistant and spore-forming bacteria, while no effect was observed against Gram-negative bacteria. In this paper we discuss a new potential antimicrobial agent, ticagrelor.

A historical, economic, and technical-scientific approach to the current crisis in the development of antibacterial drugs: Promising role of antibacterial peptides in this scenario.

The emergence of antibiotic resistance (AMR) is a global public health problem. According to estimates, drug-resistant bacteria infect 2 million patients and perish 23,000 annually. To overcome this problem, antimicrobial peptides became a potential solution based on a new mechanism of action against bacteria. This article addresses the phenomenon of antibacterial resistance in most of its nuances, responding to historical, technical-scientific, and economic aspects. Likewise, it explores new therapeutic approaches to combat multi-resistant pathogens, specifically concerning antibacterial peptides, as a potential therapeutic tool to mitigate the current crisis of antibacterial drugs. It is expected that, with technological advances, especially with the advent and adoption of artificial intelligence, there will be an increase in diversified synthetic peptide production, which can face the challenges that we have in terms of antibacterial drugs.

Antibacterial drugs and cyclodextrin inclusion complexes: a patent review.

INTRODUCTION: Bacterial antibiotic resistance occurs when bacteria mutate and escape the effect of antibiotics, which makes the antibiotics no longer effective in treating infections. New solutions for bacterial infections are a persistent need including the identification of drugs with better pharmacological profiles, more potent, and safer. Cyclodextrins inclusion complexes have been able to improve the physicochemical and pharmacological properties of the formulation molecules, resulting in new alternatives with better efficacy. AREAS COVERED: The patents analyzed in the review used treatments based on antibiotics already on the market, natural products, and synthesized molecules composed of the formulation with cyclodextrins. The combination between cyclodextrin and nanostructures also were presented in the patents review process. Moreover, inclusion complexes have been an alternative in developing treatment mainly in China by the pharmaceutical industries in several countries such as Germany, Hungary, the United States of America, Japan and China. EXPERT OPINION: This review is broad and complete since it considers the first patent involving cyclodextrins and antibacterial drugs. Therefore, the various inclusion complexes and antibacterial drugs alternatives presented in this review offer therapeutic options to fight bacterial infections. If shown to be effective, these drugs may be extremely important in the current clinical practice.

Facing Resistant Bacteria with Plant Essential Oils: Reviewing the Oregano Case.

Antibiotic resistance is a serious global threat, and the misuse of antibiotics is considered its main cause. It is characterized by the expression of bacterial defense mechanisms, e.g., ß-lactamases, expulsion pumps, and biofilm development. Acinetobacter baumannii and Pseudomonas aeruginosa are antibiotic-resistant species that cause high morbidity and mortality. Several alternatives are proposed to defeat antibiotic resistance, including antimicrobial peptides, bacteriophages, and plant compounds. Terpenes from different plant essential oils have proven antimicrobial action against pathogenic bacteria, and evidence is being generated about their effect against antibiotic-resistant species. That is the case for oregano essential oil (Lippia graveolens), whose antibacterial effect is widely attributed to carvacrol, its main component; however, minor constituents could have an important contribution. The analyzed evidence reveals that most antibacterial evaluations have been performed on single species; however, it is necessary to analyze their activity against multispecies systems. Hence, another alternative is using plant compounds to inactivate hydrolytic enzymes and biofilms to potentiate antibiotics' effects. Despite the promising results of plant terpenes, more extensive and deep mechanistic studies are needed involving antibiotic-resistant multispecies to understand their full potential against this problem.

Antibacterial Activity of Cissus incisa Extracts against Multidrug- Resistant Bacteria.

AIMS: The need to find new antimicrobial agents to cope with this phenomenon increases. BACKGROUND: Infection diseases are illness caused by different microorganisms, such as bacteria, among those caused by resistant bacteria are associated with greater morbidity, mortality and cost of the treatment than those caused by sensitive bacteria of the same species. OBJECTIVE: Need to find new antimicrobial agents to cope with this phenomenon increases. METHODS: This work carried out the study of biological activities of Cissus incisa, taking account its traditional use. Three extracts were prepared from the leaves of this plant: hexane, chloroform methanol (1:1) and aqueous. Their antibacterial and antitubercular activities were evaluated using microdilution and alamar blue assays; respectively. RESULTS: The chloroform/methanol extract (1:1) was the most active of the three tested extracts for antimicrobial activity. In this way, the extract exhibits a broad spectrum of antimicrobial activity, against the Gram positive and Gram negative bacteria tested, with MIC values between 125 to 500 µg/mL. CONCLUSION: This research contributes both to the knowledge of the Mexican flora, as well as the discovery of potential antibacterial agents derivate from plants.

Prevalencia y perfil de susceptibilidad antimicrobiana en bacterias aisladas de úlceras crónicas infectadas en adultos / Prevalence and susceptibility pattern of bacteria isolated from infected chronic wounds in adult patients

Resumen Introducción: Las úlceras crónicas son un problema de salud pública, agravándose por infecciones bacterianas causadas principalmente por agentes resistentes. Objetivo: Estudiar prevalencia y perfil de susceptibilidad en bacterias aisladas de úlceras crónicas en pacientes adultos. Pacientes y Métodos: Pacientes atendidos en la Fundación Instituto Nacional de Heridas entre mayo y julio de 2014, con úlceras crónicas en extremidades inferiores con signos inflamatorios clínicos. Las muestras fueron cultivadas en aerobiosis y anaerobiosis y para la identificación bacteriana se empleó el sistema de galerías API (Biomerieux). La susceptibilidad in vitro se evaluó según el método de Kirby Bauer. Resultados: Se reclutaron 73 pacientes, entre quienes 46 presentaron úlceras infectadas, diagnosticándose 33 úlceras venosas con predominio de infección polimicrobiana y 10 úlceras de pie diabético con predominio de infección monomicrobiana (p ≤ 0,05). Se aislaron 68 cepas de los 46 pacientes con úlcera infectada. Las enterobacterias predominaron en infección monomicrobiana (p ≤ 0,05) y los demás grupos bacterianos fueron levemente más frecuentes en infección polimicrobiana. La especie prevalente fue Staphylococcus aureus (24%) seguida de Pseudomonas aeruginosa (18%). Cincuenta cepas (77%) presentaron resistencia a uno o más antibacterianos. Destacamos resistencia de S. aureus a ciprofloxacina (50%) y cefoxitina (37,5%) identificándose así resistencia a meticilina en la comunidad (SARM-AC), siendo todas sensibles a cotrimoxazol. Las enterobacterias presentaron resistencia a sensibilidad a amikacina (95,5%), P. aeruginosa evidenció resistencia a ciprofloxacina (33,3%) con alta sensibilidad a gentamicina (91,7%) y amikacina (83,3%), mientras Acinetobacter spp presentó resistencia a ciprofloxacina y ceftazidima en 60%, con 100% de sensibilidad a imipenem. Streptococcus β hemolítico presentó 50% de resistencia a clindamicina y penicilina. Conclusión: Estos datos entregan información epidemiológica de infecciones de úlceras crónicas, representando un apoyo al diagnóstico, tratamiento y manejo de esta patología.

Background: Chronic wounds are considered a public health problem that may be complicated by bacterial infections, mainly caused by resistant strains. Aim: To study the bacteria prevalence and antimicrobial susceptibility in samples from adult patients with chronic wounds. Methods: Patients treated at National Institute of Wounds Foundation between May and July 2014, with chronic ulcers in lower extremities with clinical inflammatory signs were recluted. Samples were cultured in aerobic and anaerobic atmosphere and species identification was performed by API (Biomerieux) galleries. The in vitro susceptibility was evaluated according to the Kirby Bauer method. Results: From 73 patients, 46 had infected wounds most of them were venous ulcers (33) with prevalence in polymicrobial infections and 10 with foot-diabetes ulcers with prevalence in monomicrobial infections (p ≤ 0.05). Sixty-eight strains were isolated and Enterobacteriaceae were predominant in monomicrobial infection (p ≤ 0.05) and the other groups were slightly higher in polymicrobial infection. The main species were Staphylococcus aureus (24%) followed by P. aeruginosa (18%). Fifty strains (77%) were resistant or multi-resistance. We emphasize resistance of S. aureus to ciprofloxacin (50%) and cefoxitin (37.5%), thus identifying resistance to methicillin in the community (CA-SAMR), all of which are sensitive to cotrimoxazole. Enterobacteria showed sensitivity to amikacin (95.5%), P. aeruginosa showed resistance to ciprofloxacin (33.3%) with high sensitivity to gentamicin (91.7%) and amikacin (83.3%), while Acinetobacter spp showed resistance to ciprofloxacin and ceftazidime in 60%, with 100% sensitivity to imipenem. 50% Streptococcus β hemolytic showed resistance to clindamycin and penicillin. Conclusion: These data provide epidemiological information on chronic wound infections, representing support for diagnosis, treatment and management of this pathology.

Antibacterial Activities of Azole Complexes Combined with Silver Nanoparticles.

Growing antimicrobial resistance is considered a potential threat for human health security by health organizations, such as the WHO, CDC and FDA, pointing to MRSA as an example. New antibacterial drugs and complex derivatives are needed to combat the development of bacterial resistance. Six new copper and cobalt complexes of azole derivatives were synthesized and isolated as air-stable solids and characterized by melting point analyses, elemental analyses, thermogravimetric analyses (TGA), and infrared and ultraviolet/visible spectroscopy. The analyses and spectral data showed that the complexes had 1:1 (M:L) stoichiometries and tetrahedral geometries, the latter being supported by DFT calculations. The antibacterial activities of the metal complexes by themselves and combined with silver nanoparticles (AgNPs; 2 µg mL-1) were assessed in vitro by broth microdilution assays against eight bacterial strains of clinical relevance. The results showed that the complexes alone exhibited moderate antibacterial activities. However, when the metal complexes were combined with AgNPs, their antibacterial activities increased (up to 10-fold in the case of complex 5), while human cell viabilities were maintained. The minimum inhibitory concentration (MIC50) values were in the range of 25-500 µg mL-1. This study thus presents novel approaches for the design of materials for fighting bacterial resistance. The use of azole complexes combined with AgNPs provides a new alternative against bacterial infections, especially when current treatments are associated with the rapid development of antibiotic resistance.

Microbiologic profile of hospitalized healthcare workers / Perfil microbiológico de profissionais de saúde com internação hospitalar

Objective: according to the epidemiologic and antimicrobial resistance profile, infections are usually classified as community-acquired or nosocomial. Reports on patients without the classic criteria for nosocomial infection with multidrug-resistant germs are increasing. There is a particular concern regarding which microbiological profile must be addressed in case of infections in healthcare workers. This study was carried out with the purpose of identifying the prevalence of infection by multidrug-resistant germs in healthcare workers exposed to occupational contact with such germs at work. Methods: observational and retrospective study. In a 7-year period, healthcare worker hospitalizations were identified and the cultures results were assessed in order to identify the prevalence of infection by multidrug-resistant pathogens. Results: 1,487 healthcare workers hospitalizations were identified. In 105 of these hospitalizations, cultures were collected on the first 5 days after admission, and in 22 patients, 24 germs were identified. Multidrug-resistant pathogens were not found. Conclusion: in our sample, composed of workers from a tertiary public hospital who were hospitalized, none of the individuals presented MDR colonization or infection. These results suggest that when healthcare workers present infections, they must receive antibiotic therapy directed to community-acquired pathogens. In light of the limitations of this study, further larger and multicenter studies must be developed to enlighten such issue. .

Objetivo: conforme perfil epidemiológico e resistência antimicrobiana, as infecções costumam ser divididas entre comunitárias e nosocomiais. É crescente o relato de pacientes sem critérios clássicos para infecções nosocomiais com infecções por germes multirresistentes (GMR). Há particular preocupação perante qual perfil microbiológico deve ser coberto na presença de infecções em profissionais de saúde. Realizamos este trabalho com intuito de identificar a prevalência de infecção por GMR em profissionais de saúde expostos a contato laboral com tais germes. Métodos: estudo observacional, retrospectivo. Em um período de 7 anos, foram identificadas internações hospitalares de profissionais de saúde e aferidos resultados de culturas visando a identificar prevalência de infecção por GMR. Resultados: identificamos 1.487 internações de profissionais de saúde. Em 105 internações, foram solicitadas culturas nos primeiros 5 dias de internação. Em 22 internações, foram identificados 24 germes. Não houve isolamento de GMR. Conclusão: na amostra, composta por funcionários de um hospital público de nível terciário que apresentaram internação hospitalar, nenhum funcionário apresentou colonização ou infecção por GMR. O resultado sugere que trabalhadores da área de saúde, ao apresentar infecções, devem receber antibioticoterapia voltada para patógenos comunitários. Tendo em vista as limitações deste estudo, são necessários estudos maiores e multicêntricos para elucidar essa questão. .

Transgenic sweet orange plants expressing a dermaseptin coding sequence show reduced symptoms of citrus canker disease.

Citrus canker provoked by Xanthomonas axonopodis pv. citri is a bacterial disease causing severe losses in all citrus-producing areas around the world. Xanthomonas infection is considered as an endemic disease in Northeast and Northwest Argentina, affecting as much as 10% of commercial citrus plantations. There is not known natural resistance neither in orange varieties nor in rootstocks used for grafting of commercial cultivars. To introduce resistance to this disease, plants of Pineapple sweet orange were transformed with a genetic construct allowing constitutive accumulation of dermaseptin. In comparison with non-transformed plants, transgenic plants showed symptom reduction levels of up to 50% in in planta assays performed under controlled conditions.

Consumo comunitario de antimicrobianos en Chile, 2000-2008 / Community antibiotic consumption in Chile, 2000-2008

Background: The Chilean Ministry of Health has implemented regulatory rules for the consumption of anti-biotics since September 1999, with sales restriction limited only with medical prescription. Aim: To analyze the impact of established regulatory measures from 2000 to 2008. Material and Methods: A retrospective analysis of antibiotics sales in pharmacies from 2000 to 2008 was performed. The information was obtained from the International Marketing System (IMS Health), an auditing system of pharmacy sales. The consumption unit used was the Defined Daily Dose per 1000 inhabitants/day (DDD). Results: From 2000 to 2002 the regulatory rules had a great impact, but since 2002 the antibiotic consumption increased, especially amoxicillin, returning to similar levéis observed in 1998. Conclusions: The regulatory measures had an initial impact, but there was not reinforcement in the time and there was no further control. It is necessary to assume a permanent task and support of the authorities of health to edúcate the population about the implications of the inadequate use of antimicrobials and his effect on the microbial ecology.

Introducción: El Ministerio de Salud de Chile reguló el consumo de antimicrobianos en el mes de septiembre de 1999, mediante restricción de venta limitada sólo a venta con receta médica. El objetivo de este estudio es conocer el impacto de las medidas regulatorias entre los años 2000 y 2008. Metodología: Se realizó un análisis retrospectivo de las ventas en farmacias privadas desde el año 2000 al 2008. La información se obtuvo del International Marketing System Health (IMS Health), una empresa internacional encargada de auditar las ventas de farmacias. La unidad de consumo usada fue la DDD/1.000 habitantes-día. Resultados: A partir del año 2000 al 2002, las medidas regulatorias tuvieron un gran impacto; sin embargo, desde el año 2002 el consumo de antimicrobianos aumentó, especialmente amoxicilina, obteniéndose valores similares a los existentes en 1998. Conclusiones: Las medidas regulatorias tuvieron un impacto inicial; sin embargo, no fueron reforzadas ni controladas en el tiempo. Es necesario que las autoridades de salud del país asuman la tarea pennanente de educar a la comunidad acerca del uso inadecuado de antimicrobianos y su efecto sobre la ecología bacteriana.

Rates of antimicrobial resistance in latin america (2004-2007) and in vitro activity of the glycylcycline tigecycline and of other antibiotics

As a part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.), Gram-positive and Gram-negative bacterial isolates were collected from 33 centers in Latin America (centers in Argentina, Brazil, Chile, Colombia, Guatemala, Honduras, Jamaica, Mexico, Panama, Puerto Rico, and Venezuela) from January 2004 to September 2007. Argentina and Mexico were the greatest contributors of isolates to this study. Susceptibilities were determined according to Clinical Laboratory Standards Institute guidelines. Resistance levels were high for most key organisms across Latin America: 48.3 percent of Staphylococcus aureus isolates were methicillin-resistant while 21.4 percent of Acinetobacter spp. isolates were imipenem-resistant. Extended-spectrum β-lactamase were reported in 36.7 percent of Klebsiella pneumoniae and 20.8 percent of E. coli isolates. Tigecycline was the most active agent against Gram-positive isolates. Tigecycline was also highly active against all Gram-negative organisms, with the exception of Pseuodomonas aeruginosa, against which piperacillin-tazobactam was the most active agent tested (79.3 percent of isolates susceptible). The in vitro activity of tigecycline against both Gram-positive and Gram-negative isolates indicates that it may be an useful tool for the treatment of nosocomial infections, even those caused by organisms that are resistant to other antibacterial agents.