Until now, tracing the genealogical lines of EEC/EU Antibiotic Resistance policy has been a gap in social science research that has focused on the policies of individual countries. This Working Paper raises the question how Antimicrobial Resistance (AMR) has developed as an epistemic object in terms of biopolitical and spatial regulatory design of EEC/EU. It also asks what cultural ideas and imaginations have been associated with antibiotics since their introduction. To this end, a historical discourse analysis was conducted combining the perspectives of human geography and historical sociology. First cases of resistance occurred at short intervals with the introduction of new antibiotics in both human and veterinary medicine, and the discovery of the mechanism of horizontal gene transfer attracted global attention in the 1960s. Nevertheless, the belief in the need for an expansionary mode of production outweighed scientific doubt and the longer-term health of the population, so that regulatory interventions were more appearance than substance. Only in the wake of the geopolitical rise of the EU and BRICS countries and new ‘pandemic risks’, a general turn to security dispositif and neoliberal-individualist governmentality rearranged the coordinates of AMR policy to some extent. The interpretation of our present as a “multi-crisis”, which has become increasingly established in the “West” in the wake of climate crisis and Covid19, is apparently contributing to an increasing assessment of AMR as an unintended side-effect of an expansionary economy and lifestyle, with no regulatory responses to date that address systemic causes rather than suggesting a fiction of control.

Bakgrund: Antibiotikaresistens är ett allt större globalt problem och ett hot mot människan och deras hälsa. Utan antibiotika kommer rutinmässiga behandlingsmetoder och ingrepp inte längre kunna utföras utan stora risker och dödligheten av bakteriella infektioner kommer öka signifikant. Syfte: Syftet var att beskriva sjuksköterskans roll i att förebygga utveckling av antibiotikaresistens inom vården. Metod: En litteraturöversikt genomfördes av tio vetenskapliga artiklar. Databaserna CINAHL och PubMed användes till datainsamlingen och resultatet analyserades enligt Fribergs metod. Resultat: Utifrån dataanalysen framkom fyra teman: upprätthålla och följa riktlinjer, kommunicera och arbeta som patientförespråkare, använda uppdaterad och evidensbaserad kunskap och utbilda patienter och närstående. Slutsats: Sjuksköterskan spelar en viktig roll i förebyggandet av antibiotikaresistens. Med hänsyn till en hållbar framtid har sjuksköterskan ett ansvar för att främja hälsa hos dagens patienter samtidigt som framtida patienters hälsa inte ska äventyras. / Background: Antibiotic resistance is a growing problem globally and a threat to people and their health. Without antibiotics, routine treatment and interventions will no longer be without great risk and mortality rates from bacterial infections will increase significantly. Aim: The aim was to describe nurse’s role in preventing development of antibiotic resistance within the healthcare system. Method: A literature review of ten scientific articles was conducted. Databases CINAHL and PubMed were used for data collection and the results were analysed according to Friberg’s method. Results: Based on the data analysis, four themes emerged: maintaining and following guidelines, communicating and working as patient advocate, using updated and evidence-based knowledge, and educating patients and their families. Conclusions: The nurse plays a crucial role in preventing antibiotic resistance. Considering a sustainable future, the nurse has a responsibility to promote the health of today's patients while ensuring that the health of future patients is not compromised.

京都大学 / 新制・論文博士 / 博士(工学) / 乙第13581号 / 論工博第4212号 / 新制||工||1990(附属図書館) / (主査)教授 松原 誠二郎, 教授 中尾 佳亮, 教授 浦山 健治 / 学位規則第4条第2項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

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Antibiotic-resistant bacterial infections account for millions of human fatalities each year, with drug susceptibility testing (DST) affordability being limited by instrumentational constraints, monetary and/or time expenses. Molecular diagnostics performed at the point of care can provide a solution. Split probes coupled with label-free reporters like Fluorescent Light-up APtamers (FLAPs) are promising for point-of-care DST as they offer the needed selectivity towards point mutations inducive of drug resistance. This project aims at bridging the gap in FLAP applications for molecular diagnostics with a focus on multiplexing the analysis. Due to the limited number of DNA FLAPs available, we explored the ability of one of the most efficient DNA FLAPs - dapoxyl binding aptamer (DAP) - to bind fluorogens with different spectral properties. We performed the rational mutagenesis of the DAP dye-binding core to reveal any sequence-function correlations and to identify prospective orthogonal FLAP-dye pairs. Orthogonal FLAPs were used as scaffolds to design split dapoxyl aptameric (SDA) probes, which targeted a fragment of the katG gene from Mycobacterium tuberculosis complex associated with bacterial resistance to a first-line antituberculous drug isoniazid (INH). The probes were tested to differentiate the nucleic acid targets with single-nucleotide variations corresponding to isoniazid-susceptible (INHS) and isoniazid-resistant (INHR) bacterial phenotype in a multiplex fashion. With proper optimization of the probes, they can find an application in ratiometric analysis of heterogeneous bacterial populations composed of both drug-susceptible and drug-resistant strains and thus help in initial diagnosing of infectious diseases and in monitoring the therapy outcomes.

Neonatal sepsis caused by resistant bacteria is a worldwide concern due to the associated high mortality and increased hospitals costs. Bacterial pathogens causing neonatal sepsis and their antibiotic resistance patterns vary among hospital settings and at different points in time. This study aimed to determine the antibiotic resistance patterns of pathogens causing neonatal sepsis and to assess trends in antibiotic resistance. The study was conducted among neonates with culture proven sepsis at the University Hospital of Leipzig between November 2012 and September 2020. Blood culture was performed by BacT/ALERT 3D system. Antimicrobial susceptibility testing was done with broth microdilution method based on ISO 20776-1 guideline. Data were analyzed by SPSS version 20 software. From 134 isolates, 99 (74%) were gram positive bacteria. The most common gram positive and gram negative bacteria were S. epidermidis, 51 (38%) and E. coli, 23 (17%), respectively. S. epidermidis showed the highest resistance to penicillin G and roxithromycin (90% each) followed by cefotaxime, cefuroxime, imipenem, oxacillin, and piperacillin-tazobactam (88% each), ampicillin-sulbactam (87%), meropenem (86%), and gentamicin (59%). Moreover, S. epidermidis showed raising levels of resistance to amikacin, gentamicin, ciprofloxacin, levofloxacin, moxifloxacin, and cotrimoxazol. Gram positive bacteria showed less or no resistance to daptomycin, linezolid, teicoplanin, and vancomycin. E. coli showed the highest resistance to ampicillin (74%) followed by ampicillin-sulbactam (52%) and piperacillin (48%). Furthermore, increasing levels in resistance to ampicillin, ampicillin-sulbactam, piperacillin, and cefuroxime were observed over the years. Encouragingly, E. coli showed significantly declining trends of resistance to ciprofloxacin and levofloxacin, and no resistance to amikacin, colistin, fosfomycin, gentamicin, imipenem, piperacillin-tazobactam, and tobramycin. In conclusion, this study demonstrates that gram positive bacteria were the leading causes of neonatal sepsis. Bacterial isolates were highly resistant to first and second-line empiric antibiotics used in this hospital. The high levels of antibiotic resistance patterns highlight the need for modifying empiric treatment regimens considering the most effective antibiotics. Periodic surveillance in hospital settings to monitor changes in pathogens, and antibiotic resistance patterns is crucial in order to implement optimal prevention and treatment strategies.

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Background: COVID-19 and antimicrobial resistance (AMR) are two intersecting public health crises. Antimicrobial overuse in patients with COVID-19 threatens to contribute to the growing threat of AMR. Guidelines are fundamental in encouraging antimicrobial stewardship. We sought to assess the quality of antibiotic prescribing guidelines and recommendations in the context of COVID-19, and if these guidelines incorporate principles of antimicrobial stewardship. Methods: We performed a systematic survey which included a search using the concepts “antibiotic/antimicrobial” in September to November 2022 of the eCOVID-19 living map of recommendations (RecMap) which aggregates and summarizes guidelines across a range of international sources and all languages. Guidelines providing explicit recommendations regarding antibacterial use in COVID-19 from any jurisdiction were eligible for inclusion. Guideline and recommendation quality were assessed using the AGREE II and AGREE-REX instruments, respectively. We extracted guideline characteristics including panel representation and the presence or absence of explicit statements related to antimicrobial stewardship (i.e., judicious antibiotic use, antimicrobial resistance or adverse effects as a consequence of antibiotic use). We used logistic regression to evaluate the relationship between guideline characteristics including quality and incorporation of antimicrobial stewardship principles. Results: Twenty-eight guidelines with 63 antibiotic prescribing recommendations were included. Recommendations focused on antibiotic initiation (n=52, 83%) and less commonly antibiotic selection (n=13, 21%), and duration of therapy (n=15, 24%). Guideline and recommendation quality varied widely. Twenty (71%) guidelines incorporated at least one concept relating to antimicrobial stewardship. Including infectious diseases expertise on the guideline panel (OR 9.44, 97.5%CI: 1.09 to 81.59) and AGREE-REX score (OR 3.26, 97.5%CI: 1.14 to 9.31 per 10% increase in overall score) were associated with a higher odds of guidelines addressing antimicrobial stewardship. Conclusion: There is an opportunity to improve antibiotic prescribing guidelines in terms of both quality and incorporation of antimicrobial stewardship principles. These findings can help guideline developers better address antibiotic stewardship in future recommendations beyond COVID-19. / Thesis / Master of Public Health (MPH) / COVID-19 and antimicrobial resistance (AMR) are two serious threats to public health. Inappropriate use of antibiotics in patients with COVID-19 can worsen AMR and make future infections harder to treat. Practice guidelines can help healthcare providers prescribe antibiotics wisely. Using antibiotics carefully to reduce their harms is called antibiotic stewardship. This study evaluated the quality of practice guidelines for antibiotic prescribing in patients with COVID-19. It also assessed if the guidelines included principles of antibiotic stewardship. We searched for guidelines in a database called the eCOVID-19 living map of recommendations (RecMap). We found 28 guidelines with 63 recommendations. Identified guidelines differed widely in quality. Just over two-thirds of guidelines addressed antibiotic stewardship. Guidelines developed along with infectious disease experts and guidelines with higher recommendation quality scores were more likely to address antibiotic stewardship. Our findings can help guideline developers better address antibiotic stewardship in future recommendations.

Antibiotic resistance (AR) is a pervasive crisis that is intricately woven into social and environmental systems. Its escalation is fueled by factors such overuse, poverty, climate change, and the heightened interconnectedness characteristic of our era of globalization. In this dissertation, the impact of antibiotic usage is addressed from the perspective of wastewater-based surveillance (WBS) at the wastewater treatment plant (WWTP) and microbial ecology. Antibiotic usage and contamination was found to influence the prevalence of antibiotic resistance genes (ARGs) and resistant bacteria in both lab-scale and full-scale wastewater treatment settings. Through application of novel bioinformatic approaches developed herein, metagenomics revealed associations between sewage-associated microbes and community antibiotic use that were in part mediated by microbial ecological processes and horizontal gene transfer (HGT). In sum, this dissertation increases the arsenal of bioinformatic tools for AR surveillance in wastewater environments and advances knowledge with respect to the contribution of antibiotic use to the spread of antibiotic resistance at the community-scale. Three studies served to evaluate and/or develop bioinformatic resources for molecular characterization of AR in wastewater. Hybrid assembly combining emerging long read DNA sequencing and short read sequencing was evaluated and found to improve accuracy relative to assembly of long or short reads alone. A novel database of mobile genetic element (MGE) marker genes, mobileOG-db, was compiled in order to address short-comings with pre-existing resources. A pipeline for detecting HGT in metagenomes, Kairos, was created in order to facilitate the detection of HGT in metagenome assemblies which greatly amplified coverage of ARGs. In Chapter 5, a lab-scale study of WWTP bioreactors revealed that elevated antibiotic contamination was correlated with increased prevalence of corresponding ARGs. In addition, multiple in situ HGT events of ARGs encoding resistance to the elevated antibiotics were predicted, including one HGT event likely mediated by a novel bacteriophage. In Chapter 6, influent and effluent from a full-scale municipal WWTP were collected twice-weekly for one year and subjected to deep shotgun metagenomic sequencing. In parallel, collaboration with clinicians enabled statistical modeling of antibiotic usage and resistance, revealing associations between antibiotic prescriptions patterns in the region and resistance at the WWTP. Finally, Chapter 7 details bioinformatic recovery of diverse extended spectrum beta-lactamase gene recovery from the influent and effluent metagenomes, shedding light on the dynamics of circulating resistance genes. In sum, this dissertation identifies bioinformatic evidence for the selection of AR in wastewater environments as a result of antibiotic use in the community and advances hypotheses for explaining the mechanisms of the observed phenomena. / Doctor of Philosophy / Antibiotics are key lifesaving drugs that have dramatically improved life expectancy throughout the 20th and 21st centuries. However, there has been an increased incidence of resistance among many important bacterial pathogens in recent decades. The more antibiotics are used, the more chance that resistant bacteria can evolve, survive, and spread. Outpatient care accounts for the vast majority of therapeutic antibiotic use, with more than 200 million prescriptions written for antibiotics in 2021 in the United States. While performing a vital function in combatting disease, oral antibiotics can inadvertently harm the resident microbes of the intestinal tract (i.e., the gut microbiome) by decreasing the diversity of the microbes present and increasing the number of resistant bacteria. At a community level, antibiotic usage also has the potential to induce increased prevalence of antibiotics and antibiotic resistant bacteria in the environment as well, primarily via human excreta (urine and feces). Wastewater represents a key interface between human-derived contaminants and the environment. In regions with centralized wastewater management, antibiotics- and resistant bacteria-containing excreta are typically transported via sewage conveyance systems to a wastewater treatment plant (WWTP). At the WWTP, diverse microbes interact with and degrade various organic contaminants in a series of processes combining physical, chemical, and biological treatments. Due to the intermingling of environmental microbes, antibiotics, and antibiotic resistant bacteria, wastewater is increasingly being recognized as an important venue for antibiotic resistance surveillance and for potential interventions. Awareness of wastewater-based surveillance and epidemiology has surged as a result of the COVID-19 pandemic and such efforts are enshrined in the National COVID-19 Preparedness Plan. However, such a task is fundamentally more challenging for antibiotic resistance than for SARS-CoV-2, as it comprises multiple bacterial strains, antibiotic resistance genes, and resistance mechanisms. In this respect, DNA sequencing of wastewater, i.e., "metagenomics," holds promise as a broad monitoring tool with an unprecedented degree of biological granularity. In this dissertation, we address the impact of antibiotic usage at the WWTP from the perspective of wastewater-based surveillance. We evaluate antibiotic usage at the community-scale as a selective force among bacteria inhabiting WWTPs and identify microbial interactions that influence the escape of resistant bacteria in the effluent. A field-study of wastewater entering the WWTP and cleaned effluent water discharged by the WWTP revealed certain antibiotics and corresponding forms of antibiotic resistance were particularly prone to proliferation in the WWTP. Novel bioinformatic tools were developed and applied to the study of wastewater to reveal these associations. In sum, this dissertation advances knowledge of wastewater as both a mediator of environmental health and as a reflection of community-health in the form of antibiotic resistance.

Problem/Purpose: Antibiotic associated diarrhea (AAD) and clostridium-difficile diarrhea (CDAD) are the most common forms of infectious diarrhea in long-term care facilities. The purpose of this study was to determine the effectiveness of probiotics in preventing AAD and CDAD in the long term care geriatric population, and to identify interventions that can be used to improve clinical practice. Background/Significance: Prophylactic use of probiotics have been purported to decrease the incidences of AAD and CDAD. Previous studies have yielded contradictory results on the efficacy of probiotics. The objective of this study was to evaluate the impact of administration of probiotics on the rate of infectious diarrhea in the Long Term Care (LTC) population Method: This was a retrospective cohort study. The charts of residents of a LTC facility who were 65 years of age and older, and were administered antibiotic therapies, with or without co-administration of probiotics were reviewed. A data collection instrument was created for this study and piloted prior to its utilization. A chi-square test of independence was calculated to obtain the results. Results: Forty-four residents received probiotics with antibiotics, five cases of diarrhea were reported; no cases of CDAD were reported. In 39 residents who received antibiotics without probiotics, two cases of diarrhea and one case of CDAD were reported. Conclusion: The study showed no statistically significant evidence to support the effectiveness of probiotic use in the prevention of AAD and CDAD in a long term care facility. The incidence of AAD was higher in the group with probiotics