In a world where the human population is increasing, new innovations to produce enough food are required. Aquaculture’s part of the global animal protein production has increased in recent years and could be a possible solution. However, if aquaculture is poorly managed, it can result in negative consequences and one such consequence is the development of antibiotic resistance. In this review, I examine how aquaculture affect antibiotic resistance by studying what the literature says on accumulation of antibiotics in different organisms and sediment, if antibiotics can be transferred to humans through consumption of antibiotic treated products, and if human pathogens in aquaculture farms may acquire antibiotic resistance. Furthermore, I examine what factors are contributing to irresponsible antibiotic use and how such use is managed. The result of this review indicate that antibiotics are able to accumulate in organisms and sediment. It is not clear however how consumption of these affect human microbiomes. In contrast, it is clear that antibiotic resistance can be transferred from antibiotic-resistant bacteria to human pathogens. Regarding antibiotic use, irresponsible use foremost exists in low-income countries and the main drivers behind such use are socioeconomic ones, such as lack of knowledge, poverty and food security. Finally, I propose possible solutions that might improve future management. / I en värld där den mänskliga befolkningen ökar krävs nya innovationer för att producera tillräckligt med mat. Vattenbrukets andel av den globala animaliska proteinproduktionen har ökat de senaste åren och kan ses som en potentiell lösning. Om vattenbruk dock hanteras ansvarslöst kan det uppstå negativa konsekvenser. En sådan konsekvens är utveckling av antibiotikaresistens hos skadliga bakterier. I denna litteraturstudie undersöker jag vattenbrukets påverkan på antibiotikaresistens genom att studera vad litteraturen säger om ackumulation av antibiotika i olika organismer och sediment, om antibiotika kan överföras till människor genom konsumtion av antibiotikabehandlade produkter, och om mänskliga patogener i vattenbruksodlingar kan förvärva antibiotikaresistens. Jag undersöker också vilka faktorer som bidrar till ansvarslös antibiotikaanvändning och hur den hanteras ur ett hållbarhetsperspektiv. Resultaten i denna studie tyder på att antibiotika kan ackumuleras i organismer och sediment men att det råder oklarheter huruvida konsumtion av antibiotikabehandlad mat påverkar mänskliga bakteriekulturer. Antibiotikaresistens kan dock överföras från antibiotikaresistenta bakterier till mänskliga patogener. Ansvarslös antibiotikaanvändning sker huvudsakligen i fattigare länder och det är förmodligen i stor utsträckning till följd av socioekonomiska faktorer som okunskap, fattigdom och livsmedelstrygghet. Slutligen föreslår jag lösningar som möjligen kan bidra till bättre hantering av framtida antibiotikaanvändning.

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Pour enrayer la progression des résistances bactériennes aux antibiotiques (AB), liée, en partie, à un mésusage de ces médicaments, l’Union européenne (UE) s’est mobilisée en adoptant, en 2001, une recommandation prônant un usage prudent des AB. En 2008, sous l’égide de la Commission européenne, nous avons évalué la mise en œuvre de cette recommandation et son impact dans les Etats membres, et nous avons réalisé une analyse du cadre juridique développé dans 12 de ces Etats. De plus, une étude a été conduite entre 2005 et 2009 sur 74 établissements de santé (ES) volontaires du Sud-Ouest de la France pour identifier l’impact du cadre juridique sur l’évolution des consommations d’AB. Les Etats de l’UE ont engagé un grand nombre d’actions pour rationaliser l’utilisation des AB, mais des progrès dans le champ de l’évaluation demeurent nécessaires. Il ressort de l’analyse sur 12 Etats qu’un cadre juridique plus important semble associé à une plus grande sensibilisation de la population générale et à une meilleure maîtrise de la consommation de fluoroquinolones. Dans les ES du Sud-Ouest, les politiques locales de bon usage des AB ont progressé. Une combinaison de mesures telles que la présence d’un référent « AB », l’organisation de formations et le recours à des prescriptions à durée limitée, était associée à une réduction significative de la consommation des fluoroquinolones. L’amélioration de l’utilisation des AB implique de préciser les conditions d’efficacité optimale des actions et de renforcer l’encadrement juridique dans les Etats de l’UE, notamment en matière de surveillance, d’évaluation, de moyens d’incitation, en l’adaptant aux caractéristiques nationales. / Antimicrobial resistance (AMR) is a public health problem worldwide. As antibiotic (AB) use is one of the drivers of AMR, the Council of the European Union adopted in 2001 a recommendation on the prudent use of antimicrobial agents. To analyze the way Member States (MS) had implemented this recommendation and to approach its efficacy, we performed a survey under the auspices of the European Commission in 2008, completed by a thorough analysis of the legal framework in twelve Member States. In addition, relationships between AB stewardship programmes (ABS) and trends in AB consumption were studied from 2005 to 2009 in 74 voluntary hospitals in Southwestern France. MS had implemented a broad range of activities to improve AB use, but differences were seen namely in evaluation systems. Further analysis in 12 MS highlighted discrepancies regarding the scope of the legal framework, incentives for its enforcement, and means of evaluation. A legal framework regarding surveillance and national organisation seemed in favor of higher citizens’ knowledge and awareness and appeared to be associated with lower increase in fluoroquinolone (FQ) use. In French hospitals, ABS had sharply improved and AB consumption remained stable when adjusted on activity. The presence of an antibiotic advisor combined with provision of training and use of prescriptions with stop-orders was associated with a significant decrease in FQ use. Progress in the use of AB could be achieved by sharing experience on best practices and by enforcing legal framework, tailored to MS organisation and epidemiology, targeting activities such as surveillance and evaluation

Réduire les usages d’antibiotiques est un des leviers principaux pour contrer l’avancée de l’antibiorésistance qui menace l’efficacité du traitement des maladies bactériennes humaines et animales. En filières bovin laitier et jeunes bovins de boucherie, deux maladies de production sont responsables des principaux usages d’antibiotiques, respectivement les mammites et les maladies respiratoires. L’objectif de la thèse a été d’identifier auprès des acteurs des filières des verrous limitant l’amélioration des pratiques la diminution de l’utilisation d’antibiotiques, puis d’identifier des leviers d’action. En élevage de jeunes bovins de boucherie, des entretiens auprès d’acteurs de la filière (éleveurs et responsables) et des enquêtes auprès d’éleveurs ont permis d’identifier que l’organisation de la filière est un des principaux verrous. Cependant, les caractéristiques des systèmes d’exploitations et les compétences des éleveurs constituaient également une potentielle limite. En élevage bovin laitier, des entretiens ont permis de montrer que les perceptions et connaissances des éleveurs semblaient être un des freins majeurs à l’amélioration des pratiques, le système d’exploitation semblant intervenir à la marge. En élevage bovin allaitant, des leviers permettant d’améliorer la coordination entre les acteurs de la chaîne de valeur ont été identifiés. En élevage laitier, un programme innovant de formation et de conseil a été évalué dans le cadre d’une étude d’intervention, montrant une amélioration des connaissances et perceptions des éleveurs sur la prévention et l’utilisation des antibiotiques. / Reducing antibiotic use is one of the main levers to limit the increase of antimicrobial resistance, which threatens the effectiveness of the treatments of human and animal bacterial diseases. In dairy and young beef bull sectors, antibiotics are mainly used to control two production diseases, respectively mastitis and bovine respiratory diseases (BRD). The objective of the thesis was to identify with sectors’ stakeholders’ limitations for the improvement of antibiotic use practices, then to identify levers of action. In the young beef bulls’ sector, interviews with stakeholders and farmers showed that the organization of the value chain, because of its potential influence on BRD risk factors, was one of the main limitation identified. However, the characteristics of farming systems and farmers’ skills were also a potential limitation. In the dairy sector, interviews have shown that farmers’ perceptions and knowledge seemed to be one of the major limitation to the improvement of the practices. The farming system seemed to have only limited influence. In young beef bulls sector, levers to improve coordination between stakeholders in the value chain have been identified. In dairy farming, an innovative training and advising program was evaluated as part of an intervention study, showing an improvement in the knowledge and perceptions of farmers regarding prevention measures and antibiotic use.

L'usage excessif et inapproprié des antibiotiques a été décrit dans le monde entier depuis 25ans, tant en ville qu'à l'hôpital. En plus des effets délétères sur les patients l'utilisation abusive des antibiotiques contribue à l'émergence de résistances bactériennes et à l'augmentation des dépenses hospitalières. Dans les années 1990 plusieurs organisations du monde de la santé ont publié des plans et des recommandations visant à contrôler les consommations en antibiotiques afin de limiter la pression de sélection sur les bactéries et d'en diminuer les coûts. Au CHU de Nancy une politique de bon usage des antibiotiques a été instaurée au milieu des années 1990 puis renforcée en 2006, avec une réorganisation complète du mode prescription et de la délivrance des antibiotiques dans tout l'établissement. Une équipe opérationnelle en infectiologie (EOI) composée d'un infectiologue et d'un pharmacien est intervenue dans une partie des services afin d'améliorer la qualité des prescriptions. Pour évaluer l'impact de l'intervention de l'EOI sur les consommations antibiotique et les coûts qui en découlent, une étude contrôlée en cluster avant/après a été réalisée .Nous avons comparé les consommations globale et par classes antibiotiques ainsi que les coûts « avant » et « après » dans 2 groupes (contrôle et intervention).Les résultats ont montré qu'après l'intervention de l'EIO les consommations globales avaient diminué de 34% dans le groupe intervention et de 3% dans le groupe contrôle ( P=0,003). Pour une même activité, la réduction du coût était 14 fois plus élevée dans le groupe intervention. Nous pouvons donc avancer que l'intervention d'une EOI constitue un moyen efficace pour réduire la consommation hospitalière en antibiotiques et les coûts qui en découlent. / Overuse and inappropriate use of antibiotics has been described worldwide for about 25 years, in both community and hospital settings. In addition to its deleterious effect on patients, antibiotic misuse can lead to the emergence of bacterial resistance and increased the cost of hospitalization. Indeed, during the 1990s several organizations published plans to control the costs of antibiotics and limit selective pressure on microorganisms through surveillance and interventions promoting rational use. An antimicrobial policy has been implemented at the University Hospitals of Nancy since the mid-1990s. This antibiotic policy was therefore reinforced the beginning of 2006, changes included complete reorganization of the methods of prescribing and delivering antibiotics in all wards of the University hospitals of Nancy. In addition, an Operational Multidisciplinary Antibiotic Team (OMAT) including an infectious disease physician and a clinical pharmacist was established in some wards. To evaluate the effectiveness of this OMAT, in reducing the hospital antimicrobial consumption and costs a cluster controlled "before-after" study was performed. We compared consumption of antibiotics overall and by therapeutic class and cost savings between "before" and "after" in both groups (control and intervention). The results of this study have shown that overall consumption of antibiotics decreased after implementation of the OMAT by 34% in the intervention group and by 3% in the control group (p = 0.003). For the same activity, the total cost savings were 14-fold higher in the intervention group. Establishment of an operational multidisciplinary team may be an effective way to reduce hospital antibiotic use and cost.

The diploma thesis is devoted to issue of excessive use of antibiotics and ist consequences, the emphasis here is put especially on resistance. Due to the treatment were developed resistance stones, that did not exist earlier. Germs gained new behaviour as time went on and its sensitivity was changed to the given antibiotics. Established goals of this work were to analyse and find out which antibiotics are the most prescribed by practical doctors and what kind of antibiotics are the most used by inhabitants. The next target was to find out if people are aware of consequences of excessive use of antibiotics. The last aim was to capture the development of antibiotics consumption by inhabitants in the Czech Republic. Results show that antibiotics of the penicillin series are among the most commonly prescribed and used antibiotics, 73% of respondents have knowledge of the side effects and the consumption of antibiotics has an increasing tendency.

Introduktion: Antibiotikaresistens är idag ett av de största globala hoten mot folkhälsan. Antibiotikaresistens innebär att bakterier blir resistenta mot läkemedlet antibiotika, vilket leder till att sjukdomar som tidigare varit behandlingsbara med antibiotika blir svårbehandlade eller icke behandlingsbara. Detta leder i sin tur till högre dödlighet, längre sjukhusvistelser samt en högre kostnad för vården. Resistensen sker även naturligt men det är tydligt att överanvändning och missbrukning av antibiotikan skyndar på resistensutvecklingen avsevärt. Syfte: Syftet med den här studien är att undersöka människors beteende gällande antibiotikaanvändning utifrån ett antibiotikaresistent perspektiv. Metod: Det här är en empirisk studie som genomförts i form av en enkätundersökning.Studiedesign är en tvärsnittsdesign. Denna design innebär att data samlas in från mer än ettenda fall vid en viss tidpunkt. Studiepopulationen består av män och kvinnor i åldersgruppen18 år och uppåt utan en övre gräns.Resultat: Resultatet visar att respondenterna är medvetna om antibiotikaresistens och 88,7 %svarar att de är medvetna om att det finns antibiotikaresistens, 87,3 % följer läkarens behandlingsrekommendation. Resultatet visar att 18,3 % skulle kunna tänka sig att köpa antibiotika receptfritt på apotek utomlands utan en läkares ordination om de blir sjuka och 25 % av dem har en högskoleutbildning/universitetsutbildning. Slutsats: Generellt sett visar studien på att det finns en medvetenhet om antibiotikaresistens,vilket också visar sig i respondenternas beteende. Respondenternas beteende följer med vadsom bidrar till att resistensutvecklingen minskar i samhället som handlar om att följa läkarensbehandlingsrekommendation samt att inte köpa receptfria antibiotika. Restriktivt användandeav antibiotika bidrar till minskad resistens. / Introduction: Antibiotic resistance is today one of the biggest global threats to public health. Antibiotic resistance means that bacteria become resistant to the drug antibiotics, which leads to diseases that have previously been treatable with antibiotics becoming difficult to treat or not treatable, which in turn leads to a higher mortality, longer hospital stays and a higher cost of care. The resistance also occurs naturally, but it is clear that overuse and misuse of the antibiotic accelerates the development of resistance considerably. Aim: The aim of this study is to investigate human behavior regarding antibiotic use from an antibiotic-resistant perspective. Method: This is an empirical study conducted in the form of a survey. Study design is a cross-sectional design. This design means that data is collected from more than a single case at a given time. Study populations consists of men and women in the age group 18 years and older without an upper limit. Results: The results show that the respondents are aware of antibiotic resistance and 88.7 % answer that they are aware that there is antibiotic resistance. 87.3% follow the doctor's treatment recommendation. The results show that 18.3% could buy antibiotics without a prescription at pharmacies abroad without a doctor's prescription if they become ill and 25 % of them have a university education. Conclusion: In general, the study shows that there is an awareness of antibiotic resistance, which is also reflected in the respondents' behavior. The respondents' behavior follows what contributes to reducing the development of resistance in society, which is about following the doctor's treatment recommendation and not to buy over-the-counter antibiotics. Restrictive use of antibiotics contributes to reduced resistance.

Doctor of Philosophy / Department of Entomology / Ludek Zurek / House fly (Musca domestica L.) larvae develop in decaying organic substrates such as animal manure and adult flies likely play an important role in the ecology of fecal bacteria, including potentially virulent strains. House fly larval development strictly depends on an active bacterial community in the habitat. Although the principle of this symbiosis is not well understood, this association plays a fundamental role in transmission of microbes by this insect. In this study, enterococci were chosen as a model organism to assess the role of house flies in dissemination of multi-drug resistant bacteria in the agricultural environment. House flies (FF) and cattle manure (FM) from a cattle feedlot (frequent use of antibiotics) and house flies (BF) and manure of the American bison (BM) from the Konza Prairie Nature Preserve (no antibiotic use) were collected and analyzed. Results showed a significantly higher prevalence of enterococci resistant to tetracycline and erythromycin in FM and FF compared to that of BF and BM. Enterococcal diversity did not indicate the house fly development in manure in the corresponding habitats but the antibiotic resistance data showed very similar profiles among isolates from flies and corresponding locations. Resistance genes (tetM, tetS, tetO, ermB) and the conjugative transposon Tn916 were the most commonly detected determinants from resistant isolates from both environments. The house fly digestive tract was evaluated for the potential for horizontal transfer of antibiotic resistance genes among Enterococcus faecalis. Horizontal transfer of the pCF10 plasmid with the tetracycline resistance gene (tetM) occurred in the fly digestive tract with a transfer rate up to 101 T/D. In addition, eight enterococcal species were selected to evaluate their role and survival during house fly development. Overall, the survival rate (egg to adult) was significantly higher with E. hirae, E. durans and E. avium compared to other strains. These results indicate: a) house flies play an important role in the ecology of antibiotic resistant enterococci; b) the house fly digestive tract provides conditions for horizontal gene transfer among enterococci, and c) enterococci support the house fly development and can colonize the gut of newly emerging adult flies.

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