Abstract: Many approaches are used to discover new antibiotic compounds, one of the most widespread being the chemical modification of known antibiotics. This type of discovery has been so important in the development of new antibiotics that most antibiotics used today belong to the same chemical classes as antibiotics discovered in the 1950s and 1960s. Even though the discovery of new classes of antibiotics is urgently needed, the chemical modification of antibiotics in known classes is still widely used to discover new antibiotics, resulting in a great number of compounds in the discovery and clinical pipeline that belong to existing classes. In this scenario, the present article presents an overview of the R&D pipeline of new antibiotics in known classes of antibiotics, from discovery to clinical trial, in order to map out the technological trends in this type of antibiotic R&D, aiming to identify the chemical classes attracting most interest, their spectrum of activity, and the new subclasses under development. The result of the study shows that the new antibiotics in the pipeline belong to the following chemical classes: quinolones, aminoglycosides, macrolides, oxazolidinones, tetracyclines, pleuromutilins, beta-lactams, lipoglycopeptides, polymyxins and cyclic lipopeptides.
Abstract: There is much debate on whether continuous exposure of commensal bacteria and potential pathogens residing in the human intestinal tract to low levels of antimicrobial agents from treated food animals pose a public health concern. To investigate antimicrobial effects on bacteria under colonic conditions, we studied resistance development in Salmonella enterica and Listeria monocytogenes exposed to enrofloxacin in the presence of fecal extract. The bacteria were incubated at 37 °C in Mueller-Hinton broth, with and without 0.01~0.5 μg/mL enrofloxacin, in the presence and absence of sucrose, and with 1% or 2.5% filter-sterilized fecal extract, for three passages. In the second and third passages, only the bacteria incubated in the media containing sterilized fecal extract grew in 0.5 μg/mL of enrofloxacin. Fecal extract (1% and 2.5%) decreased the sensitivity of S. enterica to enrofloxacin in the medium containing the efflux pump inhibitors reserpine and carbonyl cyanide-m-chlorophenylhydrazone (CCCP) and affected the accumulation of ethidium bromide (EtBr) in this bacterium. Enrofloxacin (0.06 µg/mL) and fecal extract altered the composition of fatty acids in S. enterica and L. monocytogenes. We conclude that fecal extract decreased the susceptibilities of S. enterica and L. monocytogenes to concentrations of enrofloxacin higher than the MIC and resulted in rapid resistance selection.
Abstract: A total of 59,535 patients with respiratory tract infections were registered in the Happy Audit project, an audit-based, before-and-after study conducted in primary care centres of six countries (Argentina, Denmark, Lithuania, Russia, Spain, and Sweden) in 2008 and 2009. An antibiotic was explicitly requested by the patient in 1,255 cases (2.1%), with a great variation across countries ranging from 0.4%–4.9%. Antibiotics were significantly more often prescribed to patients requesting them compared to those who did not (64% vs. 28%; p < 0.001). Patients with acute exacerbations of chronic bronchitis/chronic obstructive pulmonary disease were most likely to request antibiotics while those with common colds were least likely (3.9% vs. 1.2%, respectively). The presence of tonsillar exudates and dyspnoea were more commonly associated with a demand for antibiotics. Even though physicians very often perceive that patients demand an antibiotic, the results of this study clearly show that patients only request antibiotics in a low percentage of cases. Patients were most likely to request antibiotics when they had symptoms of lower respiratory tract infections and when they came with more severe symptoms. Furthermore, there were considerable differences between countries, suggesting that the different backgrounds and traditions largely explain this variability in patients’ requests for antibiotics.
Abstract: We aimed to gain an in-depth understanding of public views and ways of talking about antibiotics. Four focus groups were held with members of the public. In addition, 39 households were recruited and interviews, diaries of medicine taking, diaries of any contact with medication were used to explore understanding and use of medication. Discussions related to antibiotics were identified and analyzed. Participants in this study were worried about adverse effects of antibiotics, particularly for recurrent infections. Some were concerned that antibiotics upset the body’s “balance”, and many used strategies to try to prevent and treat infections without antibiotics. They rarely used military metaphors about infection (e.g., describing bacteria as invading armies) but instead spoke of clearing infections. They had little understanding of the concept of antibiotic resistance but they thought that over-using antibiotics was unwise because it would reduce their future effectiveness. Previous studies tend to focus on problems such as lack of knowledge, or belief in the curative powers of antibiotics for viral illness, and neglect the concerns that people have about antibiotics, and the fact that many people try to avoid them. We suggest that these concerns about antibiotics form a resource for educating patients, for health promotion and social marketing strategies.
Abstract: Scarce and limited epidemiological, clinical and microbiological data are available regarding pediatric respiratory tract infections in the Kingdom of Morocco, a middle-income country in Northwestern Africa. Data on antibiotic usage for such infections are also scarce. A good understanding of pre-admission and intra-hospital usage of antibiotics in children with respiratory infections linked with an adequate surveillance of the antibiotic susceptibility from circulating pathogens could help policy makers improve their recommendations on management of respiratory infections. We hereby present data on antibiotic usage prior and during admission and antibiotic susceptibility of major circulating respiratory pathogens in children under five years of age admitted to the Hôpital d’Enfants de Rabat, Morocco, with a diagnosis of clinical severe pneumonia (using World Health Organization (WHO) standardized case definitions) during a period of 14 months (November 2010–December 2011), as part of a larger hospital-based surveillance study designed to understand the etiology and epidemiology of severe pneumonia cases among children.
Abstract: To explore experiences with and views of general practitioners (GPs) on a physician communication training method in primary care and its applicability and implementation in daily practice, we performed a semi-structured qualitative study of GPs’ experience of training in and implementing a communication skills training program for managing lower respiratory tract infection (LRTI) which included a seminar, simulated patient consultation together with providing and receiving feedback on ones own transcript, and a seminar in a structured approach to the LRTI consultation. Seventeen out of 20 eligible GPs who had participated in the IMPAC3T trial and were allocated to receiving enhanced physician communication training for managing lower respiratory tract infection participated. GPs’ experiences with the physician communication training method and its specific components were positive. The method gave GPs additional tools for managing LRTI consultations and increased their sense of providing evidence-based management. During the study, GPs reported using almost all communication items covered in the training, but some GPs stated that the communication skills diluted over time, and that they continued to use a selected set of the skills. The general communication items were most regularly used. Implementation of the method in daily practice helped GPs to prescribe fewer antibiotics in LRTI with the only perceived disadvantage being time-pressure. This study suggests that GPs felt positive about the physician communication training method for enhanced management of LRTI in primary care. GPs continued to use some of the communication items, of which general communication items were the most common. Furthermore, GPs believed that implementation of the communication skills in daily practice helped them to prescribe fewer antibiotics. The context-rich communication method could have wider application in common conditions in primary care.