RESUMEN
The misuse and overdose of antimicrobial medicines are fostering the emergence of novel drug-resistant pathogens, providing negative repercussions not only on the global healthcare system due to the rise of long-term or chronic patients and inefficient therapies but also on the world trade, productivity, and, in short, to the global economic growth. In view of these scenarios, novel action plans to constrain this antibacterial resistance are needed. Thus, given the proven antiproliferative tumoral and microbial features of thiosemicarbazone (TSCN) ligands, we have here synthesized a novel effective antibacterial copper-thiosemicarbazone complex, demonstrating both its solubility profile and complex stability under physiological conditions, along with their safety and antibacterial activity in contact with human cellular nature and two most predominant bacterial strains, respectively. A significant growth inhibition (17% after 20 h) is evidenced over time, paving the way toward an effective antibacterial therapy based on these copper-TSCN complexes.
Asunto(s)
Antiinfecciosos , Complejos de Coordinación , Compuestos Organometálicos , Tiosemicarbazonas , Humanos , Cobre/farmacología , Tiosemicarbazonas/farmacología , Antiinfecciosos/farmacología , Antibacterianos/farmacología , Complejos de Coordinación/farmacologíaRESUMEN
Dithiobiureas coordination chemistry towards palladium (II) ions and their possible application is presented and discussed. 1,6-(4-Methoxyphenyl)-2,5-dithiobiurea and 1,6-(4-chlorophenyl)-2,5-dithiobiurea afford two Pd(II) complexes with the general formula [Pd2(H2L)Cl2(PPh3)2]. The metal ion forms one chelate ring with the dithiobiurea, and binds to a triphenylphosphine and an additional leaving group cisplatin like. One of the complexes (1) is endowed not only with stability in DMSO and aqua solutions containing a biological buffer but also with cytotoxicity versus gastric cancer cell lines. Complex 1 does not interact covalently to DNA models, neither activates p53 or Checkpoint Kinase 1 key proteins for DNA damage response. Thus, we propose that complex 1 exerts its action by activating Mitogen-Activated Protein Kinases [p38, Extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs)] as cell death inductors.
Asunto(s)
Paladio , Transducción de Señal , Paladio/farmacología , Transducción de Señal/fisiología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Fosforilación , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismoRESUMEN
INTRODUCTION: Community Acquired Pneumonia (CAP) is common disease that can be treated in Hospital At Home (HAH). In this paper we evaluate the room of improvement in the use of antibiotics in CAP in HH. METHODS: Patients with CAP were retrospectively recruited in two Spanish hospitals from 1/1/18 to 10/30/19. Demographic, clinical and quality of antibiotic prescription variables were recorded. Subsequently, we created a new variable that collected six quality of care indicator, categorizing and comparing patients into two groups: good quality of care (4 or more indicators performed) or poor quality of care (3 or less indicators performed). RESULTS: We recruited 260 patients. The request for diagnostic tests and the adequacy to Clinical Practice Guidelines were 85.4% and 85.8% respectively. Percentages of de-escalation (53.7%) and sequential therapy (57.7%) when indicated were low. The average length of treatment was 7.3 days for intravenous and 9.5 days for total. Quality of prescription was good in 134 (63.2%) patients, being more frequent in those who were admitted directly to HAD from the emergency room. It was also associated with less readmission at 30 days. CONCLUSION: There is a wide room for improvement in some fields of antimicrobials use in HAH that could stimulate the implementation of Antimicrobial Stewardship Programs.
Asunto(s)
Infecciones Comunitarias Adquiridas , Neumonía , Antibacterianos/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Hospitales , Humanos , Neumonía/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
BACKGROUND: Detecting and managing antimicrobial drug interactions (ADIs) is one of the facets of prudent antimicrobial prescribing. Our aim is to compare the capability of several electronic drug-drug interaction (DDI) checkers to detect and report ADIs. METHODS: Six electronic DDI checking platforms were evaluated: Drugs.com®, Medscape®, Epocrates®, Medimecum®, iDoctus®, and Guía IF®. Lexicomp® Drug Interactions was selected as the gold standard. Ten ADIs addressing different mechanisms were evaluated with every electronic DDI checker. For each ADI, we assessed five dimensions and calculated an overall performance score (maximum possible score: 10 points). The explored dimensions were sensitivity (capability to detect ADI), clinical effect (type and severity), mechanism of interaction, recommended action(s), and documentation (quality of evidence and availability of references). RESULTS: The electronic DDI checkers did not detect a significant proportion of the ADI assessed. The overall performance score ranged between 4.4 (Medimecum) and 8.8 (Drugs.com). Drugs.com was the highest ranked platform in four out of five dimensions (sensitivity, effect, mechanism, and recommended action). CONCLUSIONS: There is significant variability in the performance of the available platforms in detecting and assessing ADI. Although some ADI checkers have proven to be very accurate, others missed almost half of the explored interactions.
Asunto(s)
Neumonía/epidemiología , Anciano , Anciano de 80 o más Años , Infecciones Comunitarias Adquiridas/epidemiología , Femenino , Hogares para Ancianos/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Estudios Retrospectivos , España/epidemiología , Centros de Atención TerciariaRESUMEN
BACKGROUND: Postgraduate training has the potential to shape the prescribing practices of young doctors. OBJECTIVES: To investigate the practices, attitudes and beliefs on antibiotic use and resistance in young doctors of different specialties. METHODS: We performed an international web-based exploratory survey. Principal component analysis (PCA) and bivariate and multivariate [analysis of variance (ANOVA)] analyses were used to investigate differences between young doctors according to their country of specialization, specialty, year of training and gender. RESULTS: Of the 2366 participants from France, Greece, Italy, Portugal, Slovenia and Spain, 54.2% of young doctors prescribed antibiotics predominantly as instructed by a mentor. Associations between the variability of answers and the country of training were observed across most questions, followed by variability according to the specialty. Very few differences were associated with the year of training and gender. PCA revealed five dimensions of antibiotic prescribing culture: self-assessment of knowledge, consideration of side effects, perception of prescription patterns, consideration of patient sickness and perception of antibiotic resistance. Only the country of specialization (partial η2 0.010-0.111) and the type of specialization (0.013-0.032) had a significant effect on all five identified dimensions (P < 0.01). The strongest effects were observed on self-assessed knowledge and in the perception of antibiotic resistance. CONCLUSIONS: The country of specialization followed by the type of specialization are the most important determinants of young doctors' perspectives on antibiotic use and resistance. The inclusion of competencies in antibiotic use in all specialty curricula and international harmonization of training should be considered.
Asunto(s)
Antibacterianos/uso terapéutico , Conocimientos, Actitudes y Práctica en Salud , Internacionalidad , Médicos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Estudios Transversales , Farmacorresistencia Bacteriana Múltiple , Educación de Postgrado en Medicina , Europa (Continente) , Femenino , Humanos , Infectología , Masculino , Prescripciones/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
INTRODUCTION: One of the main tools to optimize antibiotics use is education of prescribers. The aim of this article is to study undergraduate education in the field of infectious diseases, antimicrobial resistance and antibiotic stewardship from the perspective of Spanish medical students. MATERIAL AND METHODS: An anonymous online questionnaire was distributed among sixth grade students using different channels in Europe, within the ESGAP Student-Prepare survey. The questionnaire included 45 questions about knowledge, attitudes and perceptions about diagnosis, bacterial resistance, use of antibiotics and undergraduate training in infectious diseases. We present here the Spanish results. RESULTS: A total of 441 surveys were received from 21 medical schools. A total of 374 responses (84.8%) were obtained from the 8 most represented faculties, with a response rate of 28.9%. Most students felt adequately prepared to identify clinical signs of infection (418; 94.8%) and to accurately interpret laboratory tests (382; 86.6%). A total of 178 (40.4%) acknowledged being able to choose an antibiotic with confidence without consulting books or guidelines. Only 107 (24.3%) students considered that they had received sufficient training in judicious use of antibiotics. Regarding learning methods, the discussion of clinical cases, infectious diseases units rotatories and small group workshops were considered the most useful, being evaluated favorably in 76.9%, 76% and 68.8% of the cases. CONCLUSION: Medical students feel more confident in the diagnosis of infectious diseases than in antibiotic treatment. They also feel the need to receive more training in antibiotics and judicious antibiotic use.