La résistance aux antibiotiques est une menace sérieuse pour la santé publique en Europe, entrainant une augmentation des coûts de la santé, des échecs thérapeutiques, et de la mortalité (ECDC, 2011). Le développement de l'antibiorésistance est principalement lié à la consommation d'antibiotiques chez l'Homme et les animaux. Depuis le début des années 2000, les pays européens ont limité cette consommation et en 2006, l'UE a interdit l'utilisation d'antibiotiques comme promoteurs de croissance. Ceci a favorisé le développement de diverses alternatives à l'utilisation d'antibiotiques. L'objectif principal de ce projet de thèse est d'évaluer l'utilisation d'alternatives spécifiques et non spécifiques à l'utilisation d'antibiotiques dans les élevages de porcs européens. L'étude sera organisée en trois parties: i) une évaluation technique, visant à quantifier le lien entre l'utilisation d'antibiotiques et les performances techniques des élevages, ii) une évaluation économique, basée sur une analyse coût-efficacité et coûts-bénéfices des stratégies alternatives aux antibiotiques et iii) une évaluation psychosociologique, décrivant les attitudes et les comportements des éleveurs, vétérinaires et scientifiques vis-à-vis de l'utilisation d'antibiotiques en élevage porcin. Ce projet impliquera à la fois la réalisation de visites d'élevages français, l'utilisation d'outils statistiques variés et de méthodes de recherche qualitative et d'évaluation des risques. Ainsi, ce projet fournira les bases d'une compréhension globale des facteurs techniques, économiques et psychosociologiques qui orientent les décisions des éleveurs et des vétérinaires au sujet de la santé et de la production porcine et qui, par conséquent, définissent les possibles interventions sur l'utilisation d'antibiotiques. Cette étude fait partie du projet de recherche du Consortium MINAPIG financé par le programme Emida Era-Net. Un financement supplémentaire est fourni par l'Office vétérinaire fédéral suisse. / Antimicrobial resistance is a serious threat to public health in Europe, leading to mounting healthcare costs, treatment failure, and deaths (ECDC, 2011). The development of antimicrobial resistance is mainly due to antimicrobial consumption in humans and animals. From early 2000s, European countries have implemented restriction measures and in 2006, EU banned the use of antibiotics as growth promoters in animal feed. This has promoted the development of various alternatives to antimicrobial. The main objective of this PhD project is to assess and evaluate specific and unspecific alternatives to antimicrobials in the European pig industry. The study will be organised in three main parts: i) a technical assessment, quantifying the link between antimicrobial use and technical performances of the pig farms, ii) an economic evaluation, conducting cost-effectiveness and cost-benefit analyses of alternative strategies in comparison with antimicrobial usage, and iii) a psycho-sociological evaluation, describing farmers, veterinarians and pig experts attitudes, beliefs and behaviours regarding the use of antimicrobials in pig farming. The project will involve field work in France, statistical analysis using a range of methods, qualitative research methods, conceptual work and the use of risk assessment methods. We expect this PhD project to provide the foundation for an integrated understanding of technical, economical and psychological factors driving decisions of farmers and veterinarians about pig health and production and the consequential interventions, particularly the use of antimicrobials. This study is part of the MINAPIG Consortium Research project funded by the Era-Net programme Emida. Additional funding is available through the Federal Veterinary Office of Switzerland.

Surfactin, a lipopeptide surfactant and antibiotic produced by Bacillus subtilis, exhibits a strong membrane perturbation. One of the drawbacks hindering its commercial applications is the unknown mechanism of surfactin self-resistance in the producer. Therefore, the aim of this study was to examine the self-protective mechanisms of the cytoplasmic membrane of B. subtilis against the deleterious effect of surfactin. In order to reach this task, two isogenic pairs of strains differing only in surfactin production were constructed. It was found out that the early response of the producer is realized by increasing the amount of total lipid content in the membrane already with the onset of surfactin synthesis. This process leads to lowering the surfactin-lipid ratio in the membrane. In parallel with the growing surfactin concentration the content of anionic phospholipids with cardiolipin as the major representative rises up to 24 % of the total. Together with the fall of phosphatidylethanolamine these changes promote the membrane stabilization and protect it against the interaction with surfactin. These alterations result in higher rigidity both of the polar head and hydrophobic chain region of the membrane as the steady state anisotropy of DPH and TMA-DPH showed. After 24 h of cultivation induction of...

Actinobacteria, primarily the genus Streptomyces, have led to the development of a number of antibiotics, which result from their secondary metabolites or modified derivatives. Secondary metabolite production can result from competition with neighboring microbes in an effort to disrupt growth, aiding in the competition for vital nutrients in impoverished conditions. Such secondary metabolites have the potential to affect a plethora of cellular functions in target cells, including, cell wall development, protein synthesis, protein function and fatty acid synthesis/metabolism. Due to the pandemic spread of antibiotic resistant bacteria, it is imperative to continue the search for new therapeutic agents targeting these deadly organisms. As such, our group explored soil and marine samples from Tampa Bay’s surrounding farmlands and waterways for secondary metabolite producing microbes using culture methods specific to Actinobacteria. Through these efforts we isolated over 750 bacterial species, of which almost half are confirmed Actinobacteria. In an attempt to derive new and novel chemistry from these organisms, we used our novel collection, and developed techniques for epigenetic modification to un-silence dormant and cryptic metabolic pathways. Our work reveals that a number of these Actinobacteria produce secondary metabolites that are effective against the ESKAPE pathogens, some at very low concentrations. Although the bioactivity from secondary metabolites is a well-known source for antibiotic drug discovery, our epigenetic methods suggest a potential to isolate previously overlooked compounds that have a very real possibility for use as antibacterial therapeutics.

Class of 2006 Abstract / 1College of Pharmacy, University of Arizona 2El Rio Special Immunology Associates Objectives: To compare antibiotic resistance patterns of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) in HIV patients and the general population. We hypothesized that CA- MRSA strains in HIV patients may show a decreased susceptibility to trimethoprim/sulfamethoxazole (TMP/SMX) because of its widespread use for prophylaxis of Pneumocystis carinii pneumonia (PCP) in this population. Methods: Susceptibility reports for all Staphylococcus aureus isolates collected between November 1, 2004 and November 1, 2005 from Special Immunology Associates (SIA), an HIV clinic, and the neighboring Carondelet St. Mary’s Hospital Emergency Center (SMH) were analyzed. Results: Twenty-five cases in HIV patients at SIA (Mean age 40, Race: 21 Caucasian, 4 Hispanic) and 102 cases at SMH (Mean age 37, Race: 45 Caucasian, 34 Hispanic, 12 Native American, 8 African American) were identified as CA-MRSA. More than 95% of patients presented with skin infections and a seasonal peak was identified between June and October. No cases of TMP/SMX resistance were found at either institution despite the fact that 40% of the SIA patients with CA-MRSA had been exposed to TMP/SMX for PCP prophylaxis in the past. Susceptibility varied between SIA and SMH, with significant differences in susceptibility to tetracycline (57% vs. 86%, p<0.001) and levofloxacin (38% vs. 60%, p < 0.001). Erythromycin resistance in both institutions was greater than 90%. Conclusions: All CA-MRSA isolates from an HIV clinic and a neighboring health care facility were susceptible to TMP/SMX. HIV patients with CA-MRSA did not show a decrease in susceptibility to TMP/SMX, despite its routine use for prophylaxis in this population.

It was the purpose of the present investigation to determine if sensitivity to other antibiotics can likewise be affected by subjecting S. aureus to heparin contact. It is of special interest in this problem to determine whether heparin in some manner affects the combining process of penicillin with the cells of several strains of S. aureus.

Faecal pollution regularly contaminates surface waters, introducing microorganisms, including bacteria and bacteria resistant to antibiotics, to coastal waters. People can come into contact with these potentially harmful microbes when they enjoy recreational activities in the sea. Understanding the risk to bathers of acquiring infections from the sea is important for developing effective intervention strategies to protect human health. This thesis consists of four original studies which aim to answer the question ‘are bacteria in the coastal zone a threat to human health’? First, we describe a systematic review on the risk of acquiring infections from recreational use of coastal waters. Synthesising risk estimates of reporting various symptoms of ill health, we quantify this risk as well as appraise the evidence that these infections are acquired from bathing in coastal waters. The results of the second study - a large online survey - corroborate these findings and provide updated estimates of risk for UK bathers. Third, we assess the risk of ingesting antibiotic resistant bacteria among UK coastal water users. In the final study, we measured the prevalence of faecal carriage of antibiotic resistant bacteria among a highly exposed group – surfers, and in an unexposed group (non-surfers). We conclude that despite improvements made to the collection, treatment and discharge of sewage, and initiatives to communicate water quality to members of the public in recent years, people who bathe in coastal waters are still at an increased risk of adverse health outcomes, whether this is experiencing symptoms of ill health, or exposure to and colonisation by antibiotic resistant bacteria.

Antibiotic resistance is a major threat to public health. Understanding how it evolves, and the genes that underlie resistance, is the main goal of my Ph.D. research. After a resistance mutation arises, it’s fate within a pathogen population will be etermined in part by its fitness: mutations that suffer little or no fitness cost are more likely to persist in the absence of antibiotic treatment. My research centers on understanding this process better by gaining knowledge about the spectrum of fitness effects associated with antibiotic resistance mutations. Using a meta-analysis framework I find that, across a range of antibiotics and pathogens, on average single resistance mutations exhibit fitness costs in the absence of drug, however, there are instances of cost-free mutations. To evaluate the conditions leading to the persistence of resistance in the absence of antibiotic, I use experimental evolution of the opportunistic pathogen Pseudomonas aeruginosa and the antibiotic ciprofloxacin to investigate the phenotypic and genetic differences associated with constant and fluctuating drug treatment. I find that fluctuating drug treatment leads to the evolution of cost-free resistance. At the genetic level, cost-free resistance is the result of second-site mutations that compensate for the fitness cost associated with ciprofloxacin-resistance mutations. Further examination of the resistance mutations shows a lack of epistatic interactions between co-occurring mutations that confer resistance within a single isolate. To investigate the repeatability of the genetic causes of resistance, I execute a second evolution experiment using multiple clinical strains of P. aeruginosa adapting to a constant ciprofloxacin selective pressure. I find a remarkable lack of parallel evolution at the genomic level both within and between different P. aeruginosa strains. I have shown that antibiotic resistance is costly, and that these costs can be ameliorated by second-site mutations that readily arise over short time scales. Additionally, different strains of the same bacteria can gain resistance through a diverse set of genetic mutations. On an applied level these results are not positive; combating resistance evolution will be difficult because pathogens can easily compensate fitness costs of resistance, and resistance itself can be gained via a large number of genetic targets.

Since heparin combines with some antibiotics to decrease the toxicity of the antibiotic to the patient, the purpose of this investigation is to determine whether it has any effect upon the development of resistance to antibiotics by Staphylococcus aureus.

No description available.

Background: The aim of surgical antibiotic prophylaxis (SAP) is to prevent surgical site infection (SSI) by administering an appropriate antimicrobial agent perioperatively. However, SAP may be associated with adverse effects and incurs added costs. The primary objective of this prospective study is to establish whether clinicians are adhering to existing perioperative antibiotic prophylaxis guidelines in terms of indication, dosage and timing of SAP. Secondary objectives are to determine the proportion of patients receiving inappropriate antibiotics; and to evaluate correct practice concerning re-dosing and duration of SAP. Methods: A cross-sectional prospective audit of the anaesthetic records and prescription charts of surgical patients was conducted at Groote Schuur Hospital, a tertiary level teaching hospital in Cape Town, South Africa, over a period of one week. Data were collected by anaesthetists – blinded to the study objectives – and the investigators; then captured on Excel spread sheets and compared to existing SAP guidelines. Descriptive statistics and binary logistic regression were used for analysis. Results: Of the 192 patients consented, 180 questionnaires were completed for data analysis. The median age of participants was 44.5 years (IQR: 31.5-58), with a preponderance of females (58.7%). SAP was administered in 149 cases (82.8%) and withheld in 31 (17.2%). This was appropriate in 91.9% (137/149) and 77.4% (24/31) respectively. Twelve patients (6.7%) received inappropriate antibiotics and in seven (3.9%) it was inappropriately withheld. Of the 156 patients who should have received SAP, choice of drug was correct in 121 (77.6%), dosage in 110 (70.5%) and timing in 87 (55.8%). Absolute compliance was achieved in 44.4% (80/180). Errors were mostly related to timing, re-dosing and duration of SAP. Conclusion: Anaesthetists and surgeons at Groote Schuur Hospital demonstrate variable adherence to surgical antibiotic prophylaxis guidelines. Interventions aimed at improving compliance are warranted.