RESUMO
Gram-positive bacteria are among the most common human pathogens associated with clinical infections which range from mild skin infections to sepsis. Resistance towards existing class of drugs by Gram-positive bacteria including methicillin resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis (MRSE) and vancomycin resistant enterococci (VRE) is a growing concern. There is an urgent need to discover new antibiotics which are active against resistant strains of Gram positive bacteria. We report herein a novel class of spiropyrimidinetrione oxazolidinone derivatives as novel antibacterial agents. Key step towards the synthesis of title compounds involved the use of tert-amino reaction with [1,5]-hydride shift leading to the new CC bond formation. Compound 30n has demonstrated potent antibacterial activity against a panel of Gram-positive microbial strains including MRSA, MRSE, and LNZ and vancomycin resistant strains of E. faecalis. Further, molecular docking studies suggest that 30n has binding mode similar to that of LNZ in 50S RNA ribosome.
Assuntos
Antibacterianos/farmacologia , Desenho de Fármacos , Oxazolidinonas/farmacologia , Pirimidinonas/farmacologia , Compostos de Espiro/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Oxazolidinonas/síntese química , Oxazolidinonas/química , Pirimidinonas/síntese química , Pirimidinonas/química , Compostos de Espiro/síntese química , Compostos de Espiro/química , Staphylococcus epidermidis/efeitos dos fármacos , Relação Estrutura-Atividade , Enterococos Resistentes à Vancomicina/efeitos dos fármacosRESUMO
Introduction Acute pancreatitis (AP), characterized by the inflammation of the pancreas, is a common acute surgical condition accounting for approximately 3% of all surgical admissions with abdominal pain and has an incidence of approximately 56 cases per 100,000 population every year. The General Medical Council (GMC), National Institute for Health and Care Excellence (NICE), and Royal College of Nursing best practice guidelines recommend that such patients and their family members should be provided with both verbal and written information about acute pancreatitis and its management in a way that they can understand. The aim of this audit cycle was to find out the compliance with information provided to patients with acute pancreatitis as per the GMC good medical practice and NICE guidelines and assess their satisfaction. Method A closed-loop audit consisting of two cycles was carried out. Thirty patients who were admitted to the department of general surgery with acute pancreatitis were provided with a questionnaire containing 11 questions asking about the information provided to them about their condition by healthcare professionals; then, interventions were carried out in the form of developing patient information leaflets (PILs) and encouraging healthcare professionals to distribute them and provide information to the patients and their family members. Results Overall, improvements were seen in all aspects of the information being provided to patients, and particularly, more than 100% improvement was seen in patient satisfaction related to the information provided to them in the second cycle after the implementation of interventions. Conclusions This study concludes that patients should be given all the information they require in accordance with their right to information, in line with GMC best practice, NICE, and Royal College of Nursing best practice guidelines. A very effective way to improve the health outcomes and satisfaction of patients is to give them access to a patient information leaflet, which can allow patients to consider their options and understand what can happen during treatment, especially when doctors have limited time to carry out detailed discussions with the patient.