Dissertations / Theses on the topic 'Antibiotic management'

Antimicrobials are unique drugs in that they target "infectious" or "transferable" diseases. There is considerable evidence linking increasing antimicrobial use withincreasing resistance. Resistant bacteria do not know the boundaries, either between countries or within a society between hospital and primary care. Inappropriate prescribing of antimicrobials in hospitals therefore has consequences for whole communities and problems may spread both nationally and internationally. The gathering of reliable measurements of antibiotic use in hospitals employing standardised methods is essential to building an evidence base and highlighting inconsistencies at national and international levels. In this study, after data processing, validating and record linkage, a method forelectronic conversion of drug supply data to the ATC/DDD classification and forlongitudinal analysis was established for Tayside and then for a set of Europeanhospitals. Time series analysis and interrupted time series analysis were described and used for longitudinal surveillance and interventional study of antimicrobial use. This thesis explores issues concerning the evolution and management of hospital antimicrobial use using a wide range of methods. A series of drug utilisation research studies were implemented as the basis of research methods that, in combination of previously described methods, provided novel studies. No single measure can currently capture all of the aspects of hospital antibiotic use. However, a combination of detailed, point prevalence data from individual patients with longitudinal analysis of total consumption can provide meaningful data for comparison between hospitals and for analysis of the relationship between use and outcome. Additionally, there is a need to apply standard processes and novel methods to produce more meaningful surveillances. Longitudinal and point prevalence surveillances together with an explanation ofvariations in hospital characteristics are used to produce a set of coherent measurements of hospital antimicrobial use. Administrative data for longitudinal surveys requires continuous quality control.Whereas drug utilisation researchers and clinicians should target a set of indicators for interventional studies, large studies at national or international level need central data processing by country to identify targets for evaluation and for interventional studies. Support from experts in other fields is needed to address any shortcomings that may be experienced during continuous antibiotic drug utilisation monitoring at national and international levels.

A systematic review was conducted to explicitly identify interventions that alone, or in combination, were effective in improving antibiotic prescribing. The citation search strategy used in the present review provided a database of 365077 studies, of which only twenty-five were included in the final review (“review studies”). Analysis of the interventions used within the review studies indicated that a combination of “guidelines” and “pharmacy” interventions have the greatest potential to improve antibiotic prescribing. Two types of qualitative research were conducted, semi-structured interviews and the collection of naturally occurring data. Semi-structured interviews were conducted in order to determine NHS managers? perceptions of current policies used to improve antibiotic prescribing within selected Primary Care Trusts and highlighted the importance of pharmacy intervention, formularies or guidelines and improved prescribing analysis (IT based intervention) on improving antibiotic prescribing. This was supported by the collection of naturally occurring data, which was used to provide further insight into interventions used to improve antibiotic prescribing. The Specialist Antibiotic Pharmacist (HD) produced and implemented an innovative electronic antibiotic prescribing analysis tool (the Antibiotic Database) to analyse and improve antibiotic prescribing in a consistent manner. The key advantage of the Antibiotic Database was the time and money saved on producing visual electronic outputs containing an inaccurate outcome measure or time period for analysis. The results concluded that an IT based intervention, such as the Antibiotic Database should be used, in addition to the use of antibiotic guidelines and pharmacy intervention, within all sectors of the NHS in order to improve antibiotic prescribing and its analysis.

The hypotheses of this study are that reduction and rational usage of antibiotics reduces development of antibiotic resistance. In Sweden, the trends do not follow this pattern. Despite a decrease in prescriptions of antibiotics, there is an increase in the number of patients infected with Methicillin-resistant Staphylococcus Aureus (MRSA), Extended Spectrum Beta-Lactamases (ESBL) and ESBL selecting for carbapenem-resistance (ESBLCARBA). This study aims to study factors affecting antibiotic resistance management. An additional aim is to use a multidisciplinary approach for a subject that has mostly been studied with quantitative methods. First, linear regressions investigated any possible significant changes of prescription rates in outpatient care, hospital usage of antibiotic groups and antibiotic resistance. After this, nine interviews were conducted with physicians in outpatient care, hospital care and with representatives from the Swedish Strategic Programme for the Rational Use of Antimicrobial Agents and Surveillance of Resistance (Strama), a network working for Swedish prevention against antibiotics resistance. There was a significant decrease in the number of prescriptions of antibiotics in outpatient care among all Swedish counties and a small, but significant increase of antibiotics used in hospitals. The number of patients infected with multidrug resistant bacteria also show a significant increase. The interviews revealed that health care workers in all counties follow the same guidelines and try to be as specific as possible in choosing antibiotics to hit specific bacteria. The respondents suggested migration and extended travelling as explanations to the growing number of cases of multidrug resistant bacteria. Further, two major factors emerged as important for an efficient antibiotic resistance management; Education/knowledge and Discussion. The results indicate a need for further research on rational usage of antibiotics and the use of broad-spectrum antibiotics in hospital care, rather than the reduction through prescriptions. The results indicate that rational usage has a bigger impact than reduction. Using a multidisciplinary approach gave a broader perspective on the issue and future studies should see the possibilities of mixing quantitative and qualitative studies.

Rising global antibiotic resistance has caused concerns over sources and pathways for the spread of contributing factors. Majority of the antimicrobials used in the U.S. are involved in veterinary medicine, primarily with livestock rearing. Animal manure land application integrates livestock farming and agroecosystems. This manure contains antibiotic resistant elements (AREs) (resistant bacteria, resistance genes, and veterinary antibiotics) that contribute towards antimicrobial resistance. Altering manure application techniques can reduce surface runoff of other contaminants such as excess N and P, pesticides, and hormones, that can impact water quality. Conventional tillage practices in the U.S. has reduced or stopped, making subsurface injection of manure a promising option when compared to surface application. Our research compared manure application methods, manure application seasons, cropping system, and manure-rainfall time gaps to gauge the impact on AREs in the environment. Two field-scale rainfall simulation studies were conducted along with one laboratory study. Using the injection method lowered concentrations of manure associated AREs entering surface runoff. When manure was surface applied and rainfall occurred 7 d after application, 9-30 times less resistant fecal coliform bacteria (FCB) entered surface runoff when compared to 1 d time gap for that broadcast method. Within a day of manure application, antibiotic resistance gene (ARG) profiles in soil began to differ from each other based on manure application and soil ARG richness in all manure-amended soil increased compared to the background. Runoff from injection plots contained 52 ARGs with higher abundance compared to runoff from surface applied plots. ARGs in the former were more correlated to soil and more correlated to manure in the latter. The highest antibiotic concentrations were in the injection slit soil of those plots. Antibiotic concentrations in samples corresponded positively to concentrations of resistant FCB and ARGs, and there was a positive correlation between resistant FCB and their associated ARGs (Spearman's ρ = 0.43-0.63). A CRIISPR-Cas12a assay for quantification of ARGs in environmental samples was just as precise as conventional methods. There is also potential for in-situ detection. These combined results can hopefully help farmers improve manure management practices that mitigate spread of AREs to surrounding water, crops, and soil.
Doctor of Philosophy
Rising global antibiotic resistance cause concerns over sources and pathways for the spread of contributing factors. Most of the antimicrobials used in the U.S. are involved in veterinary medicine, especially with livestock rearing. Overuse of antibiotics that are medically important to human medicine compromises the effectiveness of our medicines. Animal manure contains antibiotic resistant elements (AREs) such as resistant bacteria, resistance genes, and antibiotics) that contribute towards resistance issues. Once these AREs enter the environment, they can be taken up by crops, runoff into surface water or leached into ground water, or even reside within the animal products we consume. Altering manure application techniques is beneficial for nutrient conservation but also potentially for reducing ARE spread. With our research, we compared manure application methods, manure application seasons, cropping systems, and manure-rainfall time gaps to find ways to balance the need for manure application and the spread of resistance. We used two field-scale rainfall simulation studies along with one laboratory study. Overall, using the injection method resulted in significantly lower concentrations of manure associated AREs entering surface runoff. When manure was surface applied and rainfall occurred 7 d after application, less resistant fecal coliform bacteria (FCB) entered surface runoff when compared to the 1 d time gap for broadcast methods. Within a day of manure application, antibiotic resistance gene (ARG) profiles in soil began to differ from each other and soil ARG totals in all manure applied soil increased compared to the background. Runoff from injection plots contained more soil ARGs and runoff from surface applied plots containing more manure associated ARGs. The subsurface injection method also caused highest antibiotic concentrations in the injection slit soil of those plots. High antibiotic concentrations in samples generally meant high concentrations of resistant FCB and ARGs, and resistant FCB were also found with their associated ARGs as well. A CRISPR-Cas12a assay for quantification of ARGs in environmental samples was just as precise as conventional methods. There is also potential for onsite detection. These combined results can hopefully help farmers improve manure management practices that mitigate spread of AREs to surrounding water, crops, and soil.

The research presented in this thesis explores antibiotic use and strategies to manage infection related issues within the hospital setting. In Chapter 2, the prevalence of the use of antibiotics and of HAl in hospitalised patients within Northern Ireland was explored using a point prevalence study design. This research provided details on the rate of antibiotic use and prevalence af HAI in the study sites as well as helped in the identification of targets for quality improvement of antibiotic prescribing and allowed the explanation of potential risk factors of HAl. In Chapter 3, the impact of an enhanced antibiotic stewardship programme on reducing MRSA and Clostridium difficile infection (CDI) in hospitalised patients was evaluated using segmented regression analysis within an interrupted time series. This work also involved evaluating the impact of antibiotic stewardship on the use of hi gh-risk antibiotics in the study setting. This study showed that the restriction of high-risk antibiotics contributed to both a reduction in their use and a reduction in the incidence of MRSA and CDJ in the study site hospital. Chapter 4 includes a report on the evaluation of the clinical and cost implications of blood culture contamination (Bee) within the hospital setting utilising a case-control study, comparing case samples with control samples. Length of hospital stay and total hospital resource utilisation were the main outcome measures. The results of this study indicated that BCC increased the length of hospital stay and incurred significant additional hospital costs including needless antibiotic use and extra laboratory tests. Finally, in Chapter 5, a prospective investigation was performed to evaluate the impact of an educational intervention in tackling the problem of BCC in an intensive care unit (leU). This study confinns the benefit (lower BeC rates) of continuous training and education on the proper technique for taking blood cultures in critically ill, ICU patients.

Pneumonia is a serious clinical problem with associated high mortality and morbidity. It can be potentially life threatening in the elderly and in patients with other comorbid diseases. Its clinical spectrum ranges from rapid resolution of symptoms to severe medical complications and death.

At least 1.2 million people are admitted to the hospital with pneumonia each year in the United States, and approximately 10% of these patients will die within 30 days of admission. According to the University of Maryland Medical Center, the majority of pneumonias respond well to treatment, but the infection kills 40,000–70,000 people each year. Given its public health significance, pneumonia has been the target of quality improvement activities for nearly 2 decades. This began with the publication of clinical practice guidelines in the early 1990s, was followed by a series of statewide and national quality improvement initiatives, and more recently has included public reporting and pay-for-performance programs led by the Joint Commission and the Centers for Medicare & Medicaid Services (CMS) and other payers. The aim of the study was to examine the association of antibiotic timing and reduced mortality. Data from a retrospective cohort of 550 patients hospitalized and discharged with a diagnosis of community acquired pneumonia was collected from a community hospital located in Southern California. It was hypothesized that antibiotics administered within the first six hours of hospital arrival for patients discharged with a principal diagnosis of pneumonia is associated with decreased inpatient mortality. It was noted that this association was not supported.

N. Gonorrhoeae is a major public health concern due to its capacity to develop antibiotic resistance and its potential complications including pelvic inflammatory disease, epididymitis, infertility, and disseminated infection. In order to keep up with resistance trends, the treatment recommendations for gonorrhea have changed frequently. In other areas of medicine, guideline adherence has been shown to be limited, even without frequent guideline changes. In the case of gonorrhea, inappropriate treatment can have serious individual and public health implications, making the quality of and compliance with clinical guidelines critical. This thesis is a three-part mixed methods research project assessing the development and uptake of gonorrhea treatment guidelines. We conducted a systematic review of current gonorrhea treatment guidelines and used the AGREE II tool to assess the quality of guideline development (Chapter 2). We observed that guideline quality varied greatly with many guidelines having weaknesses in their use of existing evidence to develop recommendations, their reporting of potential conflicts of interest and how they were addressed, and their consideration of barriers to the implementation of their recommendations. We then assessed physician adherence to first-line treatment recommendations in Ontario by conducting a segmented time series analysis of Ontario gonorrhea treatment data from iPHIS, the province’s reportable disease database (Chapter 3). Following the introduction of new guidelines that recommended substantial changes from current practice, we found very dramatic drops in guidelines adherence that then improved slowly over time. We then explored the use of process mapping as a tool to look at the local management of cases in the City of Ottawa by following them across the various possible treatment pathways (Chapter 4). Here, we noted differences in practice between the management of cases at Ottawa Public Health’s Sexual Health Clinic and the management of cases elsewhere in the community.

The purpose of this study was to determine the changes in prescribing habits of active members of American Association of Endodontics (AAE) with regards to antibiotics in comparison to the findings reported by Yingling et al. in 1999. The invitations to take the online survey were sent via email to 2593 active members. A response rate of 37.75% was obtained. It was determined to be adequate for analysis and for comparison to the results obtained by Yingling et al. Comparisons between the percentages shown in this survey and the previous survey were tested using a z-test. An ANOVA model was used to determine the relationships between predictive factors and the number of prescriptions written. The change in distribution of respondents was notable with an increase in younger clinicians (25% in 1999 to 36% at present). They were more likely to be in private practice and much less in part-time academic and private practice setting. The number of patients being seen per week and the number of prescriptions written per week also decreased in comparison (p<0.001). For all the considered factors, it was also noted that board certified endodontists were prescribing less antibiotics per week. A positive correlation was noted for number of years in practice (p=0.0006), type of practice (p<0.001) and number of prescriptions written per week. Changes in choice of antibiotics were also noted. There was a decrease in use of Penicillin (61.48% to 43%), an increase in the use of Amoxicillin (27.5% to 37.6%), and an increase in use clindamycin (45.3% to 64%) for patients with no medical allergies. As for patients with medical allergies, there was a steep incline in the use of clindamycin (56.03% to 90.3%) as first choice to an increase in azithromycin (7.4% to 38%) as a second choice. An improved trend was noted with a significant decrease in use of antibiotics in managing most of the endodontic scenarios given. Antibiotic use in cases of irreversible pulpitis significantly dropped from 16.76% to 12% (p<0.05); in necrotic pulps with acute apical periodontitis with no swelling, a significant decline from 53.9% to 28.3% (p<0.001); significant decreases were also noted for necrotic pulp with chronic apical periodontitis with no/mild symptoms, 18.8% to 16.1% (p=0.029), and necrotic pulp with acute apical periodontitis with swelling and mod/severe symptoms, 99.2% to 92.4% (p<0.001). An exception was noted for necrotic pulp with chronic apical periodontitis with a sinus tract where there was a significant increase in antibiotic use from 11.9% to 29.1% (p<0.001). Many clinicians (19%) were still giving antibiotics due to soliciting of patients and referring general dentists in fear of losing referrals. A disturbing find is that 50% of the respondents were using antibiotics to manage post treatment flare-ups and pain, while 13% were using antibiotics for inter-appointment pain. As for prophylactic antibiotics, most clinicians were aware of the new AHA/ADA guidelines and were abiding by them. Most of the clinicians responding to survey were choosing the appropriate antibiotics and regimen (i.e. dosage, loading dose, and duration). Although there is an improvement in trends, it has to be noted that there is still an indiscriminate and overuse of antibiotics at large. There needs to be greater improvement in the use of antibiotics in endodontics, and a group effort as a specialty is needed in halting this alarming problem of antibiotic resistance globally.

Thesis (Ph. D.)--University of California, Davis, 2004.
Degree granted in Comparative Pathology. Library does not have original title page. Also available via the World Wide Web. (Restricted to UC campuses)

The discovery of antibiotics was one of the most significant advances in modern medicine; however, our reliance on antibiotics is threatened by the spread of resistance. Antibiotic resistance is a natural phenomenon that is exacerbated by selection pressure from antibiotic use. Where prescriptions are required for antibiotics, understanding prescribing behaviour is paramount. Guidelines recommend antibiotics for respiratory tract infections (RTIs) only when pneumonia or other serious complications are suspected. Urine cultures are recommended for complicated, but not uncomplicated, urinary tract infections (UTIs). The objectives of this thesis were to identify factors related to patients, physicians, and geographic regions associated with antibiotic use for RTIs, and urine culturing for UTI; and to explore the extent of variations in these practices across physicians. A systematic review of the literature was conducted to assess factors that have previously been empirically associated with antibiotic prescribing. Then, using linked administrative datasets, factors associated with antibiotic prescriptions for paediatric respiratory tract infection were analyzed. Urine culture data was subsequently linked in, to explore urine culturing practices. These analyses demonstrated that observed physician characteristics had a stronger influence on practice patterns that did differences in patient characteristics. In particular, physicians who had been in practice for longer tended to be more likely to prescribe antibiotics, and to order urine cultures. Physicians trained outside of Canada were more likely to prescribe, but less likely to order a urine culture. Female physicians were less likely to prescribe antibiotics, and more likely to order urine cultures. The variation between physicians that remained after accounting for observed characteristics was substantial. This research demonstrates some common features of physicians that are associated with antibiotic prescribing and urine culture use. However, the variation between physicians in practice styles is greater than the effects of these characteristics. These findings have implications for the design and implementation of antibiotic stewardship efforts to improve antibiotic use. For example, audit and feedback interventions and academic detailing have shown some promise, and may be particularly effective if targeted to physicians with higher prescribing or culturing practices. This thesis demonstrates the utility of administrative datasets in identifying such physicians.
Medicine, Faculty of
Population and Public Health (SPPH), School of
Graduate

Terapia empírica com antimicrobiano de amplo espectro faz parte do manejo inicial padrão de pacientes com neutropenia febril (NF). Evidências suficientes de quais esquemas antibióticos devem ser inicialmente prescritos já existem; embora, nenhum estudo randomizado tenha avaliado se a aderência a programas de controle de antimicrobianos (PCAs) resulta em diminuição das taxas de mortalidade por esta síndrome. No presente estudo de coorte prospectivo, realizado em um hospital terciário no período de outubro de 2009 a agosto de 2011, avaliou-se o impacto da aderência ao PCA, aferida através da prescrição antimicrobiana inicial, na mortalidade em 295 episódios de NF (em 145 indivíduos adultos) que necessitaram de tratamento endovenoso hospitalar. Após análise multivariada através de regressão de Cox, incluindo outros preditores de mortalidade, a aderência ao PCA mostrou-se fator de proteção independente para morte 28 dias após início do episódio de NF (razão de hazard ajustada[HR], 0.29; intervalo de confiança de 95% [IC 95%], 0.11 a 0.72). Os fatores de risco encontrados para a não-aderência ao PCA foram presença de hipotensão (risco relativo ajustado[RR], 1.90; IC 95%, 1.37 a 2.63), diarreia (RR, 2.13; IC 95%, 1.66 a 2.73), dor perianal (RR, 2.08; IC 95%, 1.54 a 2.82), suspeita de foco infeccioso em cavidade oral (RR, 2.45; IC 95%, 1.75 a 3.43) e manifestações cutâneas de infecção (RR, 2.34; IC 95%, 1.81 a 3.04). A escolha antimicrobiana inicial é particularmente importante no manejo inicial do paciente com febre em vigência de neutropenia; a aderência ao PCA, que preconiza o uso racional de antibióticos, mostrou ser efetiva na redução de mortalidade durante o curso da doença. A presença de fatores modificadores da terapia inicial representa risco para não-adesão ao programa de controle de antimicrobianos.
Empirical therapy with broad-spectrum antimicrobial is part of the initial management of patients with febrile neutropenia (FN). Enough evidence on which antibiotics schemes should be initially prescribed already exists; however, no randomized study has evaluated whether adherence to antimicrobial stewardship programs (ASPs) results in lower rates of mortality from this syndrome. In the present prospective cohort study performed in a tertiary hospital, from October 2009 to August 2011, we evaluated the impact of adherence to ASP, measured by initial antimicrobial prescribing, in mortality of 295 episodes of FN (in 145 adults) that required intravenous inpatient treatment. After multivariate analysis through Cox regression, including other predictors of mortality, adherence to ASP proved to be an independent protective factor for death 28 days after the beginning of the episode of FN (adjusted hazard ratio [HR], 0.29; 95% confidence interval [95% CI], 0.11 to 0.72). The risk factors found to noncompliance to ASP were presence of hypotension (adjusted relative risk [RR], 1.90; 95% CI, 1.37 to 2.63), diarrhea (RR, 2.13; 95% CI, 1.66 to 2.73), perianal pain (RR, 2.08; 95% CI, 1.54 to 2.82), suspected source of infection in oral cavity (RR, 2.45; 95% CI 1.75 to 3.43) and cutaneous manifestations of infection (RR, 2.34; 95% CI, 1.81 to 3.04). The choice of antimicrobial is particularly important in the initial management of patients with fever in the presence of neutropenia; the adherence to ASP, which calls for rational use of antibiotics, was effective in reducing mortality during the course of the disease. The presence of signs or symptoms that demand changes in the initial therapy poses risks to nonadherence to the antimicrobial management program.

L’usage des produits microbiens administrés directement (aussi appelés probiotiques) gagne de l’intérêt comme alternative à l’utilisation des antibiotiques comme promoteurs de croissance dans les élevages. Cependant, très peu d’informations existent quant à l’influence des probiotiques sur la modulation du microbiote gastrointestinal et la réponse immunitaire innée chez le veau laitier. Les objectifs de cette thèse visaient à (1) Étudier l’effet de Lactobacillus acidophilus BT 1386 ou de Saccharomyces cerevisiae boulardii CNCM 1- 1079 sur les constituants sanguins, biochimiques / chimiques du sang. (2) Déterminer les mécanismes potentiels d’une réponse immunitaire renforcée de Lactobacillus acidophilus BT 1386 et de Saccharomyces cerevisiae boulardii CNCM 1-1079. (3) Déterminer comment Lactobacillus acidophilus BT 1386 ou Saccharomyces cerevisiae boulardii CNCM 1-1079 modulent la composition de la communauté microbienne GIT de veau par séquençage de nouvelle génération de la région V3-V4 du gène ARNr 16S. (4) Comparer l'efficacité de ces deux DFM avec la tetracycline-néomycine, un promoteur de croissance antibiotique. Quatre traitements ont été distribués aléatoirement à 48 veaux âgés de 2 à 7 jours (n=12). TÉMOIN : lactoremplaceur (LR) suivi d’une moulée de démarrage (MD); SCB) TÉMOIN + Saccharomyces cereviseae var. boulardii CNCM I-1079 [7,5 × 108 unités formatrices de colonie (CFU)/L de LR + 3 × 109 CFU/kg de MD]; LA) TÉMOIN + Lactobacillus acidophilus BT 1386 (2,5 × 108 CFU/L de LR + 1 × 109 CFU/kg de MD); ATB) TÉMOIN + traitement antibiotique composé de chlortétracycline (528 mg/L de LR + 55 mg/kg de MD) et de néomycine (357 mg/L de LR). Les animaux ont été élevés selon les procédures d’élevage conventionnelles pendant les 96 jours de la période expérimentale. Des échantillons de sang ont été prélevés de la veine jugulaire à différents moments pendant les périodes de pré-sevrage (jours 1 à 42), de sevrage (jours 43 à 53) et de post-sevrage (jours 54 à 96). Aux jours 33 et 96 dans chacun des groupes, 4 veaux ont été euthanasiés afin de prélever des échantillons de tissus et de digesta. Des SCB viables ont été retrouvées tout au long du tractus gastrointestinal, ainsi que dans les fèces des veaux en périodes pré- et post-sevrage. Autour du sevrage, les fèces du groupe SCB contenaient une population de lactobacilli plus importante que celles du groupe TÉMOIN. Au cours de la période pré-sevrage, la distribution des lactobacilli évoluait graduellement à travers les sections du tube digestif (colon > contenu iléal > rumen > muqueuse iléale). À l’exception du rumen, tous les autres compartiments présentaient une population de lactobacilli réduite en post- vs. en pré-sevrage. Comparativement aux groupes TÉMOIN et LA, la profondeur et la largeur des cryptes du colon des groupes SCB et ATB étaient réduites. Toujours comparativement aux groupes TÉMOIN et LA, le nombre de cellules caliciformes contenant des mucines neutres tendait à augmenter pour les groupes SCB et ATB, alors que le nombre de mucines acides augmentaient. Globalement, les traitements n’ont pas affecté les performances des animaux. Pendant le sevrage, une amélioration de la stimulation oxydative et de la phagocytose, ainsi qu’une augmentation des concentrations des protéines de la phase aiguë, ont été observées chez les groupes SCB et LA. L’ajout de probiotiques à la diète du veau a eu moins d’impact sur la diversité bactérienne mais a tout de même modifié significativement l’abondance des différentes populations microbiennes, et ce plus particulièrement dans l’iléon. L’ajout de SCB ou de LA a réduit l’abondance de certains genres bactériens pathogènes, tels que Streptococcus et Tyzzerella_4, alors que cela a augmenté l’abondance de bactéries potentiellement bénéfiques pour l’hôte tel que celles appartenant au genre Fibrobacter. Par ailleurs, d’autres bactéries bénéfiques tel que Rumminococcaceae UCG 005 et Olsenella étaient aussi plus abondantes, mais seulement pour le traitement SCB. Les bactéries pathogènes Peptoclostridium et Ruminococcus_2 étaient respectivement moins abondantes lorsque les traitements SCB et LA étaient ajoutés à la ration. Les analyses de prédiction fonctionnelle ont montré qu’en plus des effets observés sur les voies métaboliques locales impliquées dans le cycle cellulaire, la sécrétion biliaire et les voies de signalisation de l’AMPc et du proteasome, l’ajout des deux formes de probiotiques a également affecté d’importantes voies impliquées au sein d’autres tissus comme la synthèse des hormones thyroïdiennes ou le fonctionnement des synapses dopaminergiques. Cette étude suggère que les probiotiques, et plus particulièrement SCB, devraient être davantage considérés comme modulateur de la santé gastro-intestinale du veau laitier. Aussi, la supplémentation en SCB, en améliorant la réponse immunitaire innée, permettrait de stimuler le système immunitaire du veau avant l’infection, le préparant ainsi à mieux affronter les périodes plus sensibles comme celle du sevrage. Le SCB et le LA ont modifié la composition en bactéries du GIT. Dans l’ensemble, cette étude a montré une démonstration remarquable de l’importance du DFM sur le microbiote de la TI. Cependant, il faut mieux comprendre les molécules et les mécanismes qui déterminent le rôle du microbiote, puis exploiter ces connaissances pour améliorer la santé et augmenter la production animale
L’usage des produits microbiens administrés directement (aussi appelés probiotiques) gagne de l’intérêt comme alternative à l’utilisation des antibiotiques comme promoteurs de croissance dans les élevages. Cependant, très peu d’informations existent quant à l’influence des probiotiques sur la modulation du microbiote gastrointestinal et la réponse immunitaire innée chez le veau laitier. Les objectifs de cette thèse visaient à (1) Étudier l’effet de Lactobacillus acidophilus BT 1386 ou de Saccharomyces cerevisiae boulardii CNCM 1- 1079 sur les constituants sanguins, biochimiques / chimiques du sang. (2) Déterminer les mécanismes potentiels d’une réponse immunitaire renforcée de Lactobacillus acidophilus BT 1386 et de Saccharomyces cerevisiae boulardii CNCM 1-1079. (3) Déterminer comment Lactobacillus acidophilus BT 1386 ou Saccharomyces cerevisiae boulardii CNCM 1-1079 modulent la composition de la communauté microbienne GIT de veau par séquençage de nouvelle génération de la région V3-V4 du gène ARNr 16S. (4) Comparer l'efficacité de ces deux DFM avec la tetracycline-néomycine, un promoteur de croissance antibiotique. Quatre traitements ont été distribués aléatoirement à 48 veaux âgés de 2 à 7 jours (n=12). TÉMOIN : lactoremplaceur (LR) suivi d’une moulée de démarrage (MD); SCB) TÉMOIN + Saccharomyces cereviseae var. boulardii CNCM I-1079 [7,5 × 108 unités formatrices de colonie (CFU)/L de LR + 3 × 109 CFU/kg de MD]; LA) TÉMOIN + Lactobacillus acidophilus BT 1386 (2,5 × 108 CFU/L de LR + 1 × 109 CFU/kg de MD); ATB) TÉMOIN + traitement antibiotique composé de chlortétracycline (528 mg/L de LR + 55 mg/kg de MD) et de néomycine (357 mg/L de LR). Les animaux ont été élevés selon les procédures d’élevage conventionnelles pendant les 96 jours de la période expérimentale. Des échantillons de sang ont été prélevés de la veine jugulaire à différents moments pendant les périodes de pré-sevrage (jours 1 à 42), de sevrage (jours 43 à 53) et de post-sevrage (jours 54 à 96). Aux jours 33 et 96 dans chacun des groupes, 4 veaux ont été euthanasiés afin de prélever des échantillons de tissus et de digesta. Des SCB viables ont été retrouvées tout au long du tractus gastrointestinal, ainsi que dans les fèces des veaux en périodes pré- et post-sevrage. Autour du sevrage, les fèces du groupe SCB contenaient une population de lactobacilli plus importante que celles du groupe TÉMOIN. Au cours de la période pré-sevrage, la distribution des lactobacilli évoluait graduellement à travers les sections du tube digestif (colon > contenu iléal > rumen > muqueuse iléale). À l’exception du rumen, tous les autres compartiments présentaient une population de lactobacilli réduite en post- vs. en pré-sevrage. Comparativement aux groupes TÉMOIN et LA, la profondeur et la largeur des cryptes du colon des groupes SCB et ATB étaient réduites. Toujours comparativement aux groupes TÉMOIN et LA, le nombre de cellules caliciformes contenant des mucines neutres tendait à augmenter pour les groupes SCB et ATB, alors que le nombre de mucines acides augmentaient. Globalement, les traitements n’ont pas affecté les performances des animaux. Pendant le sevrage, une amélioration de la stimulation oxydative et de la phagocytose, ainsi qu’une augmentation des concentrations des protéines de la phase aiguë, ont été observées chez les groupes SCB et LA. L’ajout de probiotiques à la diète du veau a eu moins d’impact sur la diversité bactérienne mais a tout de même modifié significativement l’abondance des différentes populations microbiennes, et ce plus particulièrement dans l’iléon. L’ajout de SCB ou de LA a réduit l’abondance de certains genres bactériens pathogènes, tels que Streptococcus et Tyzzerella_4, alors que cela a augmenté l’abondance de bactéries potentiellement bénéfiques pour l’hôte tel que celles appartenant au genre Fibrobacter. Par ailleurs, d’autres bactéries bénéfiques tel que Rumminococcaceae UCG 005 et Olsenella étaient aussi plus abondantes, mais seulement pour le traitement SCB. Les bactéries pathogènes Peptoclostridium et Ruminococcus_2 étaient respectivement moins abondantes lorsque les traitements SCB et LA étaient ajoutés à la ration. Les analyses de prédiction fonctionnelle ont montré qu’en plus des effets observés sur les voies métaboliques locales impliquées dans le cycle cellulaire, la sécrétion biliaire et les voies de signalisation de l’AMPc et du proteasome, l’ajout des deux formes de probiotiques a également affecté d’importantes voies impliquées au sein d’autres tissus comme la synthèse des hormones thyroïdiennes ou le fonctionnement des synapses dopaminergiques. Cette étude suggère que les probiotiques, et plus particulièrement SCB, devraient être davantage considérés comme modulateur de la santé gastro-intestinale du veau laitier. Aussi, la supplémentation en SCB, en améliorant la réponse immunitaire innée, permettrait de stimuler le système immunitaire du veau avant l’infection, le préparant ainsi à mieux affronter les périodes plus sensibles comme celle du sevrage. Le SCB et le LA ont modifié la composition en bactéries du GIT. Dans l’ensemble, cette étude a montré une démonstration remarquable de l’importance du DFM sur le microbiote de la TI. Cependant, il faut mieux comprendre les molécules et les mécanismes qui déterminent le rôle du microbiote, puis exploiter ces connaissances pour améliorer la santé et augmenter la production animale.
There is interest in the use of direct-fed microbials (DFM) as substitutes for antibiotic growth promoters in farm animal production. However, little information exists on the effects of Lactobacillus acidophilus BT 1386 (LA) and Saccharomyces cereviseae boulardii CNCM I-1079 (SCB) on the modulation of the gastrointestinal tract (GIT) microbiota and innate immune responses in dairy calves. Therefore, the objectives of this thesis were to (1) investigate the effect of Lactobacillus acidophilus BT 1386 or Saccharomyces cerevisiae boulardii CNCM 1-1079 on blood cellular and biochemical/chemical constituents; (2) determine the potential mechanisms of enhanced immune response by Lactobacillus acidophilus BT 1386 and Saccharomyces cerevisiae boulardii CNCM 1-1079; (3) determine how Lactobacillus acidophilus BT 1386 or Saccharomyces cerevisiae boulardii CNCM 1-1079 modulate calf GIT microbial community composition by next-generation sequencing of the V3-V4 region of the 16S rRNA gene and (4) compare the efficacy of these two DFM with tetracycline-neomycin, an antibiotic growth promoter. Forty eight calves (2 to 7 days old) were randomly allocated to four treatments: 1) Control (CTRL) fed milk replacer (MR) and starter feed (SF); 2) CTRL supplemented with Saccharomyces cerevisiae boulardii CNCMI-1079 (SCB; 7.5 × 108 (CFU)/L MR + 3 × 109 CFU/kg SF); 3) CTRL supplemented with Lactobacillus acidophilus BT1386 (LA; 2.5 × 108 CFU/L MR + 1 × 109 CFU/kg SF); and 4) CTRL supplemented with antibiotics (ATB) chlortetracycline and neomycin (528 and 357 mg/L MR, respectively), and chlortetracycline (55 mg/kg SF). Animals were raised for 96 days following standard management procedures. Growth parameters (body weight and feed intake) of calves were recorded weekly. Four calves per treatment were euthanized on day 33 (pre-weaning) and an additional four calves per treatment on day 96 (post-weaning) to sample rumen and ileum tissues for real time quantitative polymerase chain reaction and colon for histomorphology. The ileum, colon and rumen were also analyzed for viability. Furthermore, samples of digesta (colon, ileum and rumen) and mucosa (colon and ileum) for bacterial characterization by sequencing the V3-V4 region of 16S rRNA gene. Weekly feces samples were collected for viability analysis. Blood samples were also collected for isolation of neutrophils and peripheral blood mononuclear cells for oxidative burst and phagocytosis analyses by flow cytometry. Serum measurements of acute phase proteins were done by ELISA. Viable SCB were recovered throughout the GIT and in the feces pre- and post-weaning. The feces of SCB-treated calves showed a greater lactobacilli population compared with CTRL (P < 0.01) around weaning. In the pre-weaning period, the distribution of lactobacilli population differed along the digestive tract (colon > ileum content > rumen > ileum mucosa; P < 0.001). The lactobacilli population were significantly reduced in all compartments (P = 0.02) post-weaning compared to pre-weaning, except in the rumen. Crypts depth and width of the colon decreased (P < 0.01) whereas number of goblet cells containing neutral mucins tended to increase (P = 0.058) while acidic mucins increased (P < 0.05) in SCB- and ATB-treated calves compared with CTRL and v LA-treated calves. Overall, growth performances were not affected by treatment. There was improvement of both oxidative burst and phagocytosis by SCB and LA during weaning in calves. Similarly, the concentrations of acute phase proteins (C-reactive proteins and serum amyloid A proteins) were increased by SCB and LA during weaning. The DFM had less impact on the bacteria diversity but had significant impact on the abundance of the bacteria community with most changes associated to treatments occurring in the ileum. SCB and LA reduced some pathogenic bacteria genera such as Streptococcus, Tyzzerella_4 and increased some potential beneficial bacteria such as fibrobacter. Meanwhile, Rumminococcaceae UCG 005 and Olsenella, also beneficial, were increased only by SCB treatment. The potential pathogenic bacterium, Peptoclostridium, was reduced by SCB only while LA reduced Ruminococcus_2. The functional prediction analyses indicated that besides affecting local pathways such as cell cycle, bile secretion, proteasome or cAMP signaling pathway, both DFM might also affect important pathways in other tissues such as thyroid hormone synthesis or Dopaminergic synapse in the brain. Our results suggest that SCB is a modulator of gastrointestinal health and could prime the immune system prior to infection leading to an enhanced innate immune response in calves especially during periods of stress (e.g., weaning). Consequently, SCB might have the potential to strengthen calf immune system in the critical periods of disease susceptibility. Both SCB and LA changed the bacteria composition of the GIT. Overall, this study showed a remarkable demonstration of the importance of DFM on the GIT microbiota. However, what is needed is a complete and better understanding of the molecules and mechanisms driving the roles played by the microbiota and then to exploit this knowledge to improve health and increase animal production.

This thesis deals with problem solving of general practitioners (GPs), which is explored with different methods and from different perspectives. The general aim was to explore and describe rules of thumb and to analyse the management of respiratory and urinary tract infections (RTI and UTI) in general practice in Sweden. The results are based upon focus group interviews concerning rules of thumb and a prospective diagnosis-prescription study concerning the management of patients allocated a diagnosis of RTI or UTI. In addition unpublished data are given from structured telephone interviews concerning specific rules of thumb in acute sinusitis and prevailing cough.

GPs were able to verbalize their rules of thumb, which could be called tacit knowledge. A specific set of rules of thumb was used for rapid assessment when emergency and psychosocial problems were identified. Somatic problems seemed to be the expected, normal state. In the further consultation the rules of thumb seemed to be used in an act of balance between the individual and the general perspective. There was considerable variation between the rules of thumb of different GPs for patients with acute sinusitis and prevailing cough. In their rules of thumb the GPs seemed to integrate their medical knowledge and practical experience of the consultation. A high number of near-patient antigen tests to probe Streptococcus pyogenes (Strep A tests) and C-reactive protein (CRP) tests were performed in patients, where testing was not recommended. There was only a slight decrease in antibiotic prescribing in patients allocated a diagnosis of RTI examined with CRP in comparison with patients not tested. In general, the GPs in Sweden adhered to current guidelines for antibiotic prescribing. Phenoxymethylpenicillin (PcV) was the preferred antibiotic for most patients allocated a diagnosis of respiratory tract infection.

In conclusion, the use of rules of thumb might explain why current practices prevail in spite of educational efforts. One way to change practice could be to identify and evaluate rules of thumb used by GPs and disseminate well adapted rules. The use of diagnostic tests in patients with infectious illnesses in general practice needs critical appraisal before introduction as well as continuing surveillance. The use of rules of thumb by GPs might be one explanation for variation in practice and irrational prescribing of antibiotics in patients with infectious conditions.

On the day of the public defence the status of the articles IV and V was: Accepted.

In urban karst areas, such as the City of Bowling Green, Kentucky and the Tampa Bay Metropolitan Area, groundwater quality faces a variety of threats. The development of residential, commercial, and industrial landuse types allows for a wide variety of groundwater pollutants to enter the karst groundwater systems. Various different models and indices have attempted evaluative approaches to identify issues in urban karst areas, but the methods vary by location and lack a focus on urban karst groundwater quality. There also exists a lack of a data-driven approach that is able to capture short- and long-term changes in threats to groundwater quality as a result of urbanization. The overall purpose of this study was to develop a holistic, data-driven evaluation toolbox with threat, vulnerability, and monitoring assessment tools for urban karst groundwater systems to better determine the possible threats, data collection needs, monitoring parameters, and analytical approaches needed to ensure groundwater quality is maintained in urban karst regions. This study focused on: 1) determining what indicators, parameters, resolution, and data quality need to be prioritized to create an effective, holistic monitoring framework for urban karst groundwater, and 2) developing an effective assessment and evaluative tools for urban karst groundwater quality sites using historic and modern data in an urban karst setting. The outcomes include an Urban Karst Aquifer Resource Evaluation (UKARE) Toolbox with a Threat, Vulnerability, and Monitoring evaluation tools that were applied and validated through application of the Toolbox using case studies in the City of Bowling Green, Kentucky and the Tampa Bay Metropolitan Area in Florida. The results demonstrate the universal applicability of the UKARE Toolbox to different urban karst sites and its effectiveness at scoring for threats and vulnerabilities, as well as identifying potential monitoring sites through primary data collection of water quality parameters and emerging pathogens at over 150 sites between both study areas. The final results of this study are useful to develop monitoring and management plans through a standardized scoring and evaluation tool in order to influence urban karst groundwater monitoring and management.

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CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
A capacidade da cianobactéria Microcystis aeruginosa de formar colônias vem sendo apontada como importante característica frente a adversidades ambientais, como por exemplo proteção contra predação e a criação pela mucilagem de um microambiente favorável às células. Entretanto, a formação de colônias e seus mecanismos e vantagens ainda não são completamente compreendidos. Neste estudo o principal objetivo foi contribuir para a compreensão do papel de diferentes morfotipos (unicelular e colonial) na ecofisiologia de M. aeruginosa. Em ambientes naturais, florações de cianobactérias ocorrem predominantemente na forma colonial, entretanto, por questões técnicas, os experimentos são realizados tradicionalmente com culturas unicelulares. Portanto, a intensão desta tese foi contribuir para desenvolvimento de técnicas para o manejo de florações de cianobactérias utilizando uma abordagem ambientalmente mais realista através da realização de experimentos com culturas coloniais. Nossos resultados apontaram que a forma colonial de M. aeruginosa promoveu uma vantagem na proteção das células contra agentes químicos como peróxidos, de forma que a aplicação de doses mais altas pode ser necessária no caso de mitigação de florações com predominância de Microcystis colonial. Além disso, as doses de peróxido capazes de causar a liberação significativa de microcistinas (MC) pelo morfotipo unicelular não aumentaram a concentração de MC liberada pelo morfotipo colonial. Na avaliação dos efeitos dos antibióticos, o morfotipo colonial apresentou maior resistência ao antibiótico oxytetraciclina, enquanto que o antibiótico enrofloxacina afetou igualmente ambos os morfotipos. Além disso, o morfotipo unicelular desenvolveu resistência a oxytetracyclina mais rapidamente do que o morfotipo colonial. Desta forma, sugerimos que o rápido desenvolvimento de resistência ao antibiótico deve ser cuidadosamente levado em consideração. Por fim, ao testar o método de Flock & Sink, a aplicação de lastro removeu significativamente a biomassa do morfotipo colonial enquanto o morfotipo unicelular demandou a aplicação de lastro e coagulante. A conclusão geral da tese é que os morfotipos de M. aeruginosa influenciam significativamente o efeito de diferentes substâncias químicas utilizadas com o objetivo de controlar o crescimento de cianobactérias. Enfatizamos que para o manejo de florações de cianobactérias é necessária uma cuidadosa análise sistêmica e da comunidade de cianobactérias antes da tomada de decisões para a aplicação de medidas de mitigação.
The ability of Microcystis aeruginosa to form colonies has been identified as an important characteristic of the species to face environmental adversities, such as protection against predation and the creation by the mucilage of a microenvironment favourable to cells. However, the colony formation and their mechanisms and benefits are not yet fully understood. In this study, the main objective was to contribute to the knowledge of the role of different morphotypes (unicellular and colonial) in the ecophysiology of M. aeruginosa. In the environment, cyanobacterial blooms occur mainly as the colonial form but, due to technical issues, the experiments are traditionally carried out with unicellular cultures. Therefore, we intended to contribute to the development of techniques for cyanobacterial blooms management by using a more realistic environmental approach running experiments with colonial cultures. Our results pointed out that the colonial form of M. aeruginosa promoted an advantage in the protection of the cells against peroxides, so a higher dose application may be necessary for mitigating blooms in which the colonial form is predominant. Furthermore, the peroxide doses capable of causing significant release of microcystins (MC) by the unicellular morphotype did not increase the MC released by the colonial morphotype. Evaluating the effects of antibiotics, the colonial morphotype showed highest resistance to the antibiotic oxytetracycline, while the antibiotic enrofloxacin affected both morphotypes equally. In addition, the unicellular morphotype developed resistance to oxytetracycline more rapidly than the colonial morphotype. In this way, we suggest that the rapid development of antibiotic resistance should be carefully taken into consideration. Finally, when testing the Flock & Sink method, the application of ballast removed significantly the biomass of the colonial morphotype, while the unicellular morphotype required application of ballast and coagulant. The general conclusion of the thesis is that the morphotypes of M. aeruginosa significantly influence the effect of different chemical substances used to control the growth of cyanobacteria. We emphasize that for the management of cyanobacterial blooms is mandatory a thoroughly analysis of the system and of the cyanobacterial community prior to the decision making for an application of mitigation measures.

Orientador: Adriana Polachini do Valle
Resumo: A infecção de sítio cirúrgico é uma das complicações mais importantes e frequentes no cuidado do paciente, gerando grande ônus ao mesmo e à instituição. A profilaxia antimicrobiana é uma das principais ferramentas no combate à essas infecções, contudo, estudos apontam elevadas taxas de erros em seus processos, aumentando o risco de infecção de sítio cirúrgico e o prolongamento da internação e gastos hospitalares. Este estudo objetivou desenvolver e validar um aplicativo para auditoria e controle da profilaxia antimicrobiana em sítio cirúrgico para dispositivos móveis, baseando-se no protocolo adotado pela Comissão de Controle de Infecção Relacionada à Assistência à Saúde (CCIRAS) do Hospital das Clínicas de Botucatu e pesquisas recentes da instituição. O desenvolvimento do aplicativo foi realizado utilizando a ferramenta Xamarin, que permite o desenvolvimento de aplicativos de maneira multiplataforma. A validação foi realizada por meio de entrevistas com 10 especialistas de áreas que trabalham diretamente com profilaxia antimicrobiana, onde foram avaliados a usabilidade, apresentação e informações do modelo proposto. Nestas entrevistas, utilizou-se do Índice de Validação de Conteúdo (IVC) e Coeficiente de Kappa para avaliação da concordância entre os juízes, sendo definido como valores mínimos ideais de 0.75 e 0.61, respectivamente. A validação do sistema demonstrou excelentes resultados, onde os itens avaliados apresentaram uma boa classificação, com IVC igual ou superior a ... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Surgical site infection is one of the most important and frequent complications in patient care, generating a great burden on the patient and the institution. Antimicrobial prophylaxis is one of the main tools for the prevention of these infections; however, studies indicates that there are high error rates in this process, which can increase the risk of surgical site infection, prolong hospitalization time and increases hospital expenses. This study aimed to develop and validate a mobile application to audit and control antimicrobial prophylaxis in surgical site process, based on the protocol adopted by the Infection Control Committee related to Health Care (ICCHC) of the Hospital das Clínicas de Botucatu, and recent researches at the institution. The development of the system was carried out using the Xamarin development platform, which allow the development of multiplatform applications. The validation process was conducted with interviews from 10 experts that works directly in areas related to antimicrobial prophylaxis, evaluating the usability, presentation and information of the proposed model. In those interviews, the Content Validity Index (CVI) and Kappa Coefficient were used to evaluate the concordance between the judges, having defined as ideal minimum values of 0.75 and 0.61, respectively. The system’s validation showed excellent results, where all the evaluated items received a good classification, with a CVI equal to or higher than 0.90 and Kappa Coefficient equ... (Complete abstract click electronic access below)
Mestre

Antimicrobial resistance is an international public health problem and is associated with increased morbidity, mortality, and healthcare costs. Antibiotic consumption, particularly indiscriminate use of these agents, is recognised as a major cause of resistance. Clinical guidelines recommend that in otherwise healthy individuals, antibiotics should not be used in the management of acute dental conditions, in the absence of spreading infection and systemic upset. Instead, a surgical intervention should be the first-line treatment for such problems. This thesis describes the use of antibiotics for acute dental conditions in primary care in the UK, and explores factors that influence prescribing for dental problems using a mixed methods approach.

Antibiotics and antibiotic resistance genes from animal manure applied to soil as fertilizer are now among the most concerned contaminants in soil. The widespread use of antibiotics in livestock might amplify the risk of developing antibiotic resistance, causing once treatable diseases to turn deadly. The World Health Organization declared antibiotic resistance as "one of the biggest threats to global health, food security, and development". The goal of this dissertation was to develop best manure management practices by understanding the behavior of manure-associated antibiotics in manure, water, and soil. In particular, my research focused on the effects of manure application methods, on-site manure treatment methods, manure application seasons, and manure-rainfall time gaps on antibiotic surface runoff losses, antibiotic distribution and movement in soil, antibiotic dissipation in soil, and development of antibiotic resistance. Rainfall simulation field-scale and soil incubation lab studies were combined to find the best manure management practices. My research has shown for the first time that using the manure soil subsurface injection method, especially during spring application season due to moist soil, applying manure at least 3 days before a subsequent rainfall, and using composted manure, can significantly reduce the quantity of antibiotic loss with runoff from manure-applied fields to the surrounding environment. The majority of applied antibiotics remained in soil. All antibiotics showed a similar dissipation pattern with fastest kinetics during the first 14 d before slowing down. The effect of two manure application methods on antibiotic dissipation kinetics varied with different antibiotics. Although the half-life of tested antibiotics in soil was short (<21 days), some remained detectable even at 6 months after a single manure application. Results also showed that compared to the surface application, the subsurface injection slits acted as a "hot zone" with a higher amount of antibiotics, manure microbes, and antibiotic resistance. The results provide information for policy makers, manure managers, and farmers to develop better manure management practices that can use manure as fertilizer while minimizing the spread of antibiotics to surrounding water, soil, and plants.
Doctor of Philosophy

Antimicrobial resistance (AMR) has been classified as one of the phenomena that belongs to the current top threats to human health. AMR is the process where bacteria become resistant to the antimicrobial drug and renders the antibiotic ineffective. This phenomenon is increasing exponentially due to misuse and overuse of antibiotics and is responsible for 700,000 annual deaths globally. If the contributing factors to AMR remain persistent, the estimated amount of annual deaths will increase to the exorbitant figure of 10 million by 2050. The inappropriate waste discharge from antibiotic manufacturing plants is the third major cause contributing to AMR. For this reason, environmental sustainability within the pharmaceutical industry is tightly linked to human health, and therefore, the importance of environmental risk management becomes crucial. Pharmaceutical supply chains are extremely complex, fragmented, and rigid due to the highly regulated environment and global distribution of the chains. Constant availability is sometimes compromised, and this leads to national shortages of antibiotics, which increase AMR. Therefore, supply chain sustainability risks (SCSRs) need to be thoroughly assessed and managed. The thesis aims to identify the sustainability risks that threaten the constant supply of antibiotics and further provide a comprehensive and sufficient framework on how to assess and manage SCSRs within the pharmaceutical industry. This research is based on the review of existing literature, followed by an empirical study that included a case study of two specific antibiotics relevant to the Swedish market. The analysis of publicly available databases, together with the qualitative interviews, revealed that the most susceptible node of the supply chain resides in the primary manufacturing stage. The most relevant SCSRs have been identified, and an adapted framework is suggested. The role of regulatory agencies has been demonstrated to be fundamental to achieve change concerning environmental progress. Further research needs to be implemented for the validation of the suggested framework within a practical context.

This dissertation addresses the history of antibiotic use in British and US food production between 1950 and 2013. Introduced to agriculture in the 1950s, antibiotics underpinned the 20th-century revolution in Western food production. However, from the late 1950s onwards, controversies over antibiotic resistance, residues and animal welfare began to tarnish antibiotics' image. By mapping both the enthusiasm and the controversies surrounding antibiotic use, this dissertation shows how distinct civic epistemologies of risk influenced consumers', producers' and officials' attitudes towards antibiotics. These differing risk perceptions did not emerge by chance: in Britain, popular animal welfare concerns fused with new scenarios of antibiotic resistance and drove reform. Following 1969, Britain pioneered antibiotic resistance regulation by banning certain feed antibiotics. However, subsequent reforms were only partially implemented, and total antibiotic consumption failed to sink. Meanwhile, scandals and public pressure forced the American FDA to install the first comprehensive monitoring program for antibiotic residues. However, differing public priorities and industrial opposition meant that the FDA failed to convince Congress of resistance-inspired bans. The transatlantic regulatory gap has since widened: following the BSE crisis, the EU phased out growth-promoting antibiotic feeds in 2006. The US proclaimed only a voluntary and partial ban of antibiotic feeds in December 2013. In the face of contemporary warnings about failing antibiotics, the dissertation shows how one group of substances acquired different meanings for different communities. It also reveals that the dilemma of antibiotic regulation is hardly new. Despite knowing about antibiotic allergies and resistance since the 1940s, no country has managed to solve the dilemma of preserving antibiotics' economic benefits whilst containing their medical risks. Historically, effective antibiotic regulation emerged only when differing perceptions of antibiotics were broken down either by sustained regulatory reform or large crises.

Before the availability of antibiotics minor infections could become life threatening. Nurses working in voluntary and public hospitals in Britain were exposed to such risks. This thesis uses both oral testimonies and published sources in order to examine their practices concerning the management of infection risks. The detail of nursing work in this period has been generally hidden in nursing histories of the 1930s and 1940s which have addressed mainly political, recruitment, educational, registration and status issues. Whilst these histories may comment about menial duties, and the culture and discipline in clinical areas, they lack detailed exploration of the day-to-day work of the nurse. This novel study contributes to redressing the balance by examining nursing practice between the discovery of penicillin in 1929 and its widespread availability in Britain in 1948. Data analysis, including the oral testimonies of nineteen former nurses who worked between 1929 and 1948, suggests that nursing practice during this period placed enormous emphasis on cleanliness and hygiene. It is argued that this was linked to sanitarianism which influenced nursing practice before its replacement by germ theory. Probationer nurses learnt their skills in managing infection risks to themselves and their patients in a disciplined and safe way. This was achieved through the exercise of strict routines and a hierarchy of tasks that provided a graduated exposure to the patient and infection risks. This thesis draws on debates in the literature about purity, vocation and status to explore, and add weight to this argument. The analysis also identifies that the introduction of sulphonamide drugs and antibiotics altered nursing practices in the management of both infection risks and patients with infection. Whilst the full effects of these changes are not examined in this thesis, it is argued that the significant impact of these drugs was such that the emphasis on cleaning and hygiene became diminished in importance and nursing had to redefine its role. It suggests that more prominence needs to be given to changes in clinical practice in the history of nursing. This study breaks new ground by suggesting the rigorous training of nurses in cleaning and hygiene tasks was needed in order to manage the infection risks faced by nurses before the availability of antibiotics.

Background Development of resistance to first line antimalarials led to recommendation of artemisinin based combination therapies (ACTs). High adherence to ACTs provided by community health workers (CHWs) gave reassurance that community based interventions did not increase the risk of drug resistance. Integrated community case management of illnesses (ICCM) is now recommended through which children will access both antibiotics and antimalarials from CHWs. Increased number of medicines has been shown to lower adherence. Objective To compare adherence to antimalarials alone versus antimalarials combined with antibiotics under ICCM in children less than five years. Methods A cohort study was nested within a cluster randomized trial that had CHWs treating children less than five years with antimalarials and antibiotics (intervention areas) and CHWs treating children with antimalarials only (control areas). Children were consecutively sampled from the CHWs' registers in the control areas (667 children); and intervention areas (323 taking antimalarials only and 266 taking antimalarials plus antibiotics). The sampled children were visited at home on day one and four of treatment seeking. Adherence was assessed using self reports and pill counts. Results Adherence in the intervention arm to antimalarials alone and antimalarials plus antibiotics arm was similar (mean 99% in both groups) but higher than adherence in the control arm (antimalarials only) (mean 96%). Forgetfulness (38%) was the most cited reason for non-adherence. At adjusted analysis: absence of fever (OR = 3.3, 95%CI = 1.6–6.9), seeking care after two or more days (OR = 2.2, 95%CI = 1.3–3.7), not understanding instructions given (OR = 24.5, 95%CI = 2.7–224.5), vomiting (OR = 2.6, 95%CI = 1.2–5.5), and caregivers' perception that the child's illness was not severe (OR = 2.0, 95%CI = 1.1–3.8) were associated with non-adherence. Conclusions Addition of antibiotics to antimalarials did not lower adherence. However, caregivers should be adequately counseled to understand the dosing regimens; continue with medicines even when the child seems to improve; and re-administer doses that have been vomited.

Throughout this thesis I have laid out several factors that have contributed to the sustainability of shrimp farming in Thailand, and if sustainability whilst maintaining production can ever be achieved. To find out the current situation of shrimp farming in Thailand, the history of global and Thai shrimp farming is described. The social and environmental problems of the unsustainable history of shrimp farming in Thailand is then considered. Solutions to these effects conclude that it is up to the consumer to demand for better regulations from the government and the shrimp companies to ensure a sustainable future for shrimp farming both globally and in Thailand.

Peu étudiée et méconnue, initialement décrite au début du XXe siècle, Helicobacter pylori fut redécouverte en 1982 par deux chercheurs australiens, JR Warren et BJ Marshall. Ils soutinrent que la plupart des ulcères gastro-duodénaux étaient causés par cette bactérie, et non par le stress ou la nourriture épicée, comme pensé auparavant. Cette découverte révolutionna le monde de la gastroentérologie et leur valut le prix Nobel de physiologie et de médecine 2005. Environ la moitié de la population mondiale est colonisée par H. pylori au niveau de l'estomac. Dans 10 à 20% des cas, l'infection peut évoluer vers un ulcère gastro-duodénal et dans certains cas vers une transformation maligne. Cette infection se soigne classiquement à l'aide d'une trithérapie associant 2 antibiotiques à un inhibiteur de la pompe à protons pour neutraliser l'acidité gastrique.

Notre travail de recherche a consisté à analyser la proportion de patients infectés par H. pylori dans une cohorte de plus de 22.000 patients, issus de divers groupes ethniques, vivant en Belgique. Ces souches de H. pylori, isolées dans notre laboratoire, à partir des biopsies gastriques, ont aussi servi à une étude pour suivre l'évolution de la résistance aux antibiotiques ces 20 dernières années afin de proposer des améliorations de la prise en charge thérapeutique de l'infection à H. pylori en Belgique.
Doctorat en Sciences biomédicales et pharmaceutiques
info:eu-repo/semantics/nonPublished

L'elaborato è inerente alla presenza di residui e contaminanti nel latte. Contaminanti come micotossine, metalli pesanti, antibiotici ed ormoni, che possono essere trasmessi attraverso diversi modi come ad esempio foraggi o mangimi contaminanti, aria inquinata o trattamenti eseguiti sull'animale, in particolare uso di antibiotici. Se presenti in quantità elevate questi possono destare problemi alla salute del consumatore. È stata descritta inoltre la relazione fra management in allevamento e presenza di residui nel latte, quindi come prevenire l'esistenza di questi contaminanti con una corretta gestione dell'animale e le operazioni ad esso connesse, in particolare facendo riferimento ad igiene e pulizia degli ambienti e dell'animale stesso. Diversi sono i metodi utilizzati per la rilevazione di questi contaminanti nel latte, quali ad esempio metodo HPLC, test ELISA e altri, più o meno sensibili a seconda del residuo di interesse.

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Evaluation of antimicrobials in hospital is complex and multifaceted detail, where the monitoring can contribute greatly to therapeutic efficacy and reduction in hospital costs. The work aims to describe the profile of hospital use of antibiotics in children with restricted use, in an attempt to contribute to reducing costs, improving hospital management and monitoring of hospital infections, bringing to patient safety and therapeutic efficacy leading to better quality of life, as well as the monitoring system of audit of antibiotics, identification of pharmacotherapeutic profile and rational use of medicines in accordance with pre-established clinical protocols. It is a retrospective cross-sectional study conducted from August to October 2008 in the pediatric HMDO service. Data collection was performed through the software internal use of the hospital, with specificity in two modules of the system of hospital infection and management of hospital admission and, recognizing and monitoring the therapeutic antibiotics in children according to clinical protocols of the unit of hospitalization. All these data were taken from the internal information system of the hospital so online. Data were collected as the type of infection, infection of the topography, lists of antibiotics used, dosage, route of administration, frequency, duration of treatment. The antimicrobials used were selected according to the pharmaceutical form, dose prescribed and the corresponding volume. There was no use of antimicrobials in accordance with the pre-clinical protocols established by the institution. It is appropriate therapeutic use of antibiotics through a check list, a systematic control of fulfillment of the prescription of antibiotics, continued education of prescribers and compliance with clinical protocols.
Avaliação de antimicrobianos a nível hospitalar é um processo complexo minucioso e multifacetado, onde o monitoramento pode contribuir muito para eficácia terapêutica e diminuição de custos hospitalares. O trabalho visa descrever o perfil de utilização de antimicrobianos hospitalares de uso restrito em pediatria, na tentativa de contribuir para a diminuição de custos, melhoria da gestão hospitalar e monitoramento das infecções hospitalares, trazendo ao paciente segurança e eficácia terapêutica que levem à melhor qualidade de vida, bem como no acompanhamento do sistema de auditoria de antibióticos, identificação do perfil farmacoterapêutico e uso racional de medicamentos de acordo com protocolos clínicos pré-estabelecidos. Constitui-se de um estudo transversal retrospectivo realizado no período de agosto a outubro de 2008 no serviço de pediatria do HMDO. A coleta de dados foi realizada através do softwear de uso interno do hospital, com especificidade em dois módulos do sistema de infecção hospitalar e gerenciamento de unidade hospitalar e internação, reconhecendo e monitorando os antibióticos terapêuticos em pediatria, de acordo com protocolos clínicos da própria unidade de internação. Todos estes dados foram extraídos do sistema de informação interno do hospital de forma on line. Foram coletadas informações como o tipo de infecção, topografia da infecção, listas dos antibióticos utilizados, dose, via de administração, freqüência, duração do tratamento. Os antimicrobianos consumidos foram selecionados de acordo com a forma farmacêutica, dose prescrita e volume correspondente. Observou-se não conformidade na utilização de antimicrobianos com os protocolos clínicos pré-estabelecidos pela instituição. Propõe-se adequação na utilização dos antibióticos terapêuticos através de um check list, um controle sistemático do preenchimento da prescrição de antimicrobianos, educação continuado de prescritores e cumprimento de protocolos clínicos.

Antimicrobial resistance (AMR) is the process where the bacteria develop resistance towards the treating effect of an antibiotic drug. AMR poses an alarming threat to human health causing around 700,000 deaths per year around the globe. If appropriate measures to combat the resistance are not taken, the number of deaths globally could increase to around 10 million by the year 2050. There are various factors driving the growth of AMR of which antibiotic shortages are common. A clear insight into the pharmaceutical supply chain is necessary to understand the reasons causing antibiotic unavailability. Ensuring access to medicines is one of the major objectives of pharmaceutical supply chains. Pharmaceutical firms compete in a volatile market to increase their profits. Antibiotics render slim profit margins to pharmaceutical firms; declining profits and increasing costs of production have led to firms outsourcing their operations to suppliers in different geographical locations. This in turn forms complex supply chain structures with various actors of a single drug chain being dispersed across the globe. The complexity in these supply chains lead to antibiotic supply interruptions. National drug shortages drive the risk of AMR, and these shortages are caused when pharmaceutical supply chains are weak or fragile. Therefore, the pharmaceutical supply chains need to be thoroughly analysed. This thesis aims to explore the different possible upstream supply chain structures that could exist in pharmaceutical supply chains. The study also highlights the factors that motivate the firms to choose different supply chain structures. This research is based on the existing literature on pharmaceutical supply chains. Qualitative semi-structured interviews, reports and existing research articles guided the authors in building a typology of upstream pharmaceutical supply chains based on: how different processes are handled by the MAH, the geographical location of operations in the chain, and the sourcing strategy of the Market Authorisation Holder (MAH) who owns the license for the drug. The findings of this study outline how a pharmaceutical firm could possibly structure the upstream supply chain based on its strategies. This study is limited to conceptualizing only the actors involved in the direct supply chain of the focal firm (MAH), further research including actors in the extended supply chain needs to be performed to get deeper insights into pharmaceutical supply chains.

Yes
During January 15th – 17th, 2017 a group of scientists met, under the auspices of the UK-India Centre for Advanced Technology for Minimizing Indiscriminate Use of Antibiotics, to discuss the further developments and potential solutions to antimicrobial resistance. This was the third work shop under this funding stream held in Hyderabad. The presentations and outcomes of the workshop are released here. Key out comes included the need to address improved treatment and detection of TB, delivery of antimicrobial peptides, potential strategies for combating beta-lactam resistance.
Medical Research Council

Background Inappropriate antibiotic prescribing is a key contributor to increasing antibiotic resistance. Despite the standard practices promoted through clinical practice guidelines (CPGs), treatment regimens are not always in accordance with these guidelines. In Australia, a significant proportion of inappropriate antibiotic prescriptions in hospitals and primary care is due to noncompliance with CPGs. This is further exacerbated by the difficulty faced by clinicians in integrating and managing multiple information streams at the point of care to inform evidence-based decision- making. There is increasing recognition that digital health interventions such as clinical decision support systems (CDSS) may assist in optimising antimicrobial management. CDSS provide treatment recommendations based on patient-specific risk factors and research evidence, allowing clinicians to provide personalised care. Many studies provide evidence of the potential of CDSS for promoting optimal antibiotic management; however, adoption of these systems in clinical practice remains low. In addition to this lack of effective system adoption, there is a high rate of clinicians’ ignoring or overriding the systems’ recommendations or only engaging with partial use of the systems’ features. These factors limit the efficacy of CDSS in improving antibiotic prescribing. Objective The objective of this thesis was to evaluate individual, organisational, and system-level factors that impact CDSS implementation for evidence-based antibiotic management. An understanding of the different aspects of CDSS implementation in Australia has been sought by bringing together the perceptions and experiences of different stakeholders. The project aimed to achieve this objective by i) synthesising the evidence on the efficacy of CDSS for antibiotic management; ii) understanding clinicians’ perceptions regarding CDSS use for optimal antibiotic prescribing; and iii) evaluating the challenges of integrating CDSS into the healthcare system. Methods To achieve the objectives outlined above, the thesis was divided into four studies: In study I, a systematic review and meta-analyses were conducted to evaluate the impact of CDSS implementation on various clinical and economic outcomes associated with antibiotic management. The study protocol was developed using the PRISMA-P checklist. Studies were selected using specific pre-defined study eligibility criteria. Studies providing sufficient data on the outcomes were included in the meta-analyses to calculate pooled effect estimates of the impact of CDSS implementation on antibiotic management. In studies II & III, a cross-sectional online survey was conducted in Australia. Clinicians directly involved in prescribing, administering, and managing antibiotics in hospital and primary care settings were invited to participate. We adopted the Unified Theory of Acceptance and Use of Technology (UTAUT) model to understand factors contributing to clinicians’ inappropriate antibiotic prescribing behaviour and their behavioural intent to adopt CDSS. Using this framework, we also examined the role of moderating factors such as gender, age, clinical experience, and care settings in shaping users’ behaviour in adopting CDSS. We used multivariate logistic regression models to investigate the association between these moderating factors and users’ perceptions regarding CDSS adoption. Finally, in study IV, we used a qualitative approach to conduct in-depth interviews with policymakers involved in the implementation and evaluation of CDSS in Australia. The focus of this study was to understand what is required to effectively scale-up CDSS implementation from pilot studies to a system-wide innovation. Participants shared their experiences and perceptions concerning the gaps and challenges in the Australian healthcare system for integration of CDSS into healthcare processes. The interview transcripts were thematically analysed to establish a contextual understanding of the system-wide challenges for CDSS implementation. Results Results from this research highlight that CDSS can help reduce the risk of inappropriate antibiotic prescribing by increasing compliance with prescribing guidelines. The findings further indicate that CDSS can improve antibiotic prescribing by reducing the volume of overall antibiotic use, duration of therapy, length of hospital stay and thereby decreasing the overall cost of therapy. However, most of the evidence included in our systematic review was from studies having moderate to low methodological quality. Non-randomised studies tended to overestimate the effect of CDSS on appropriate antibiotic management, compared to randomised studies. However, the direction of the effect was largely consistent across both study types and favoured the positive impact of CDSS for antibiotic management. There was also substantial statistical heterogeneity in the results across the included studies which can be explained by the large variability in CDSS adoption across studies. Findings from the survey with clinicians indicated that different individual and setting specific characteristics are important factors that influence clinicians’ perceptions regarding CDSS adoption and lead to variability in uptake across different clinicians. Experienced clinicians were more sceptical of using CDSS for clinical decision-making, potentially due to limited digital health literacy, mistrust in the information provided by CDSS and fear of compromising their professional autonomy. Similarly, in comparison to users, CDSS non-users were more likely to lack trust in CDSS recommendations and fear compromising their professional autonomy due to CDSS adoption. A lack of transparency and explainability in CDSS design, in which end-users are not aware of how systems have computed recommendations can reduce their trust in CDSS. Consistent with the context of primary care, primary care clinicians believed that time constraints and patient expectations were important drivers of CDSS adoption. These findings highlight that the efficacy of CDSS implementation may be limited by a lack of consideration of contextual factors such as clinical experience, setting of use, and users’ skills which impact the users’ behaviour to adopt CDSS. Targeted clinician engagement, digital health literacy and better communication of the reliability of information provided may assist with more successful implementation of CDSS at point of care. Interviews with Australian policymakers further explored system-level challenges and gaps that may impede successful CDSS implementation. The results show that the lack of shared vision between different stakeholders, and the fragmented infrastructure within the healthcare system are major barriers to the integration of CDSS within existing processes in the healthcare system. CDSS implementation needs to be supported by an effective governance structure that can establish clear roles, prioritise investment in health system capacity building and incorporate cross-discipline and inter-organisational collaboration for quality data sharing. The ability of CDSS to ensure coordinated and interoperable care by exchanging information across organisations requires mutually agreed data standards at a national level. There is a need to establish standards not only for generating data in a standardised format, but for semantic interoperability that allows data communication and interpretation across different systems. Notwithstanding the significance of standardisation to ensure interoperability in CDSS, our findings also highlight that this standardisation must be balanced with adequate flexibility in the CDSS design and implementation process, so that user and setting specific requirements can be incorporated to improve adoption. Conclusion In conclusion, our findings illustrate that CDSS reflects best practice for antibiotic management through evidence-based clinical decision making, integrating the knowledge base, and flagging medication errors. The integration of these systems in healthcare settings is, however, challenging due to the complex interaction between the system, organisational and human factors. The findings from our research suggests that individual and setting characteristics such as clinical experience, use of CDSS and the type of setting, influence the clinicians’ perception of CDSS role in antibiotic management. These characteristics provide a better understanding of why CDSS adoption varies across different clinicians and care settings. We also found that the lack of synergy evident between multiple stakeholders and organisations - who seem to have varying interests and objectives regarding CDSS implementation - is limiting the ability to develop a shared vision and collaborative action. These findings provide evidence firm foundation for policymakers for developing a holistic CDSS implementation framework that considers the interaction of the system within the context of organisational and human behavioural characteristics. Implementation processes need to be tailored to specific user and setting requirements for improved adoption and use of CDSS by clinicians. A better understanding of the clinical culture would support successful CDSS implementation, along with effective strategies to develop broader digital literacy, methods for sustaining clinicians’ engagement with the technology, and approaches to facilitating cross-discipline collaboration.
Thesis (Ph.D.) -- University of Adelaide, School of Public Health, 2022

Acute respiratory tract infection (ARI) is the most common reason for outpatient medical visits in the United States, and frequently results in treatment with an antibiotic. Most ARIs have a viral etiology, thus antibiotic therapy will have little clinical benefit in these cases. It is estimated as much as one-half of all antibiotic utilization for ARI in outpatient settings is inappropriate. Importantly, this misuse is thought to be the primary driver of antibiotic resistance development among bacteria. Antibiotic resistant infections cause an estimated 2 million illnesses and 23,000 deaths annually in the United States, and associated costs exceed $30 billion. Despite our current understanding of relevant predictors of appropriate antibiotic use, less is known regarding seasonality. This dissertation explores effects of seasonality on antibiotic prescribing in three aspects: 1) seasonal variation in appropriateness of prescribing, and antibiotics prescribed among common ARIs; 2) specific predictors of observed seasonal variation in prescribing practices; and 3) implications of seasonality for guideline concordance & quality of care. Findings generated herein, could help inform interventions designed to promote more judicious use of antibiotics in healthcare.

Bovine mastitis is the most prevalent disease in the production of dairy cattle worldwide. The present study aimed to characterize the main etiological agents of mastitis and the corresponding susceptibility patterns in 700 milk samples submitted to the Azorean regional laboratory in 2013. A questionnaire was also performed to determine the relationship of the isolated agents with different types of management practices and features of the dairy farms that produced the analyzed milk samples. Environmental agents were the ones more frequently isolated namely Escherichia coli and Streptococcus uberis. Contagious agents were less frequently isolated, of which Staphylococcus aureus was the most frequently isolated. Amoxicilin plus clavulanic acid was the antibiotic combination to which a larger number of agents was susceptible to. Some management practices were significantly associated with the isolation of certain bacteria in mastitic milk samples, namely the extension of the dry periods and the use of internal teat sealant.

Decreasing surface water quality in South Africa has become an issue of concern as the population grows, industrial and agricultural activities expand, and environmental pollution increases. Wastewater treatment plants and other anthropogenic activities are liable for releasing raw and inadequately treated effluents into the surface water. Extensive pollution accompanied by the use of disinfectants, pesticides, and other chemical pollutants has been attributed to increased antimicrobial resistance in bacteria such as Escherichia coli in surface water, increasing environmental antibiotic resistance spread. The research aimed to determine water quality and prevalence of antibiotic-resistant bacteria in Naauwpoortspruit River, eMalahleni, Mpumalanga Province. Five sampling sites were selected along the Naauwpoortspruit River and monitoring was done for seven consecutive months. Samples were collected and analysed for physicochemical, microbiological parameters, and susceptibility profile of antibiotic-resistant bacteria using standard methods. Pearson correlation analysis was used to assess the path and strength of the relationship between physicochemical and microbiological parameters in the study area. Results of physicochemical and microbial parameters showed variation throughout the selected study sites. The results revealed a pH range of 4.45 – 7.9 and electrical conductivity levels range of 58.63 - 113.3 mS/m for the different sampling sites during the study period with lower levels detected during the winter period and higher levels in the summer period. Also, water samples showed a high total dissolved solids levels range of 381.1 – 736.45 mg/L and biochemical oxygen demand range of 67.1 – 168 mg/L for the different sampling sites during the study period. The Naauwpoortspruit River had higher levels of ammonia of 33.4 mg/L at Point A during the winter period as compared to 15 mg/L in the summer period. Heavy metals results showed that mercury range of 0.01 – 0.065 mg/L and copper range of 0.001 – 0.0035 mg/L were not compliant with aquatic ecosystem guidelines at all selected sites throughout the study period. The foremost finding of this study was that E. coli were present in all the selected sites at concentrations (>100 cfu/100ml). Elevated concentrations of 5.4 x 103 and 4.2 x 103 cfu/100ml for the total and faecal indicator bacteria were detected from sites downstream to 2.2 x103 and 2.35 x103 cfu/100ml for sites upstream river, in the rainy months. During the dry season, total coliforms, and faecal coliforms concentration of 0.4 x103 to 0.65 x 103 cfu/100ml were detected downstream and 0.25 x 103 and 0.5 x 103 cfu/100ml from upstream, respectively. The physicochemical and microbiological parameters measured at selected sites exceeded acceptable limits and proved unsuitable for applications such as full and intermediate recreational activities, and aquatic ecosystems. The variation in physicochemical parameters results was influenced by both natural processes and human activities such as salinity and Acid Mine Drainage (AMD) within the Naauwpoortspruit River. Using the Kirby-Bauer disc diffusion method, E. coli and faecal coliforms were tested for resistance to antibiotics; ampicillin (10 μg/ml), kanamycin (30 μg), streptomycin (30 μg), chloramphenicol (30 μg), erythromycin (15 μg), ox tetracycline (30 μg), erythromycin (15 μg/ml) and norfloxacin (10 μg). More than 60% of faecal coliform were resistant to at least four of the tested antibiotics and between 60 - 80% of the E. coli isolates were resistant to β lactam. The highest microbial antibiotic resistance (MAR) index value was observed at Site D (0.38 for E. coli) which showed multi-antibiotic resistance. Site D is characterized by wastewater treatment, power generation industries, and agriculture activities. The highest level of MAR observed at Site D indicates the need to control extensive pollution and constantly monitor the changing trends in antimicrobial resistance patterns of these waterborne pathogens. Statistical analysis showed that the development of microbiological parameters loads has a strong correlation with physicochemical parameters due to the association of sampling sites in the river environment. This study shows that the aquatic ecosystem needs constant monitoring to establish their conditions, impacts of pollution activities within the catchment, and input information into sustainable management of the water resources.
Environmental Sciences
M. Sc. (Environmental Science)

Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina
Contextualização: Endocardite de válvula cardíaca protética (EVP) trata-se deuma complicação grave da Endocardite Infeciosa (EI), que atinge 1-6% dos indivíduoscom próteses valvulares e traduz 10-30% dos doentes com EI. Associa-se acomplicações severas e alta morbilidade e mortalidade. A abordagem a EVP carece deum plano de gestão rápido, objetivo e multidisciplinar a fim de resguardar o doenteevitando a morte e complicações graves associadas, recorrendo a antibioterapia ecirurgia frequentemente.Objetivo: Proporcionar ao leitor uma perspetiva integral do tema, desde a suaepidemiologia, contextualização, microbiologia e fisiopatologia associada, aapresentação clinica típica, a abordagem diagnóstica e terapêutica (com suaslimitações), profilaxia de doentes de alto risco, prognóstico associado, e por último osdesafios e as perspetivas futuras.Material e Métodos: Procedeu-se à pesquisa de artigos na base de dadosPubMed. Abrangeu-se neste trabalho artigos desde 1984 a 2020, com ênfase nosartigos dos últimos dez anos, cingindo-se a fontes em literatura inglesa e francesa.Resultados: Utilizou-se um conjunto de fundamentos para restringir a extensapesquisa efetuada, aos quais se destaca as palavras chave utilizadas, o autor dosartigos, a data da publicação, o tipo de estudo e metodologia aplicadas nos mesmos.Assim, após leitura cuidadosa dos títulos e resumos dos artigos encontrados,selecionou-se com base nos fundamentos acima mencionados 53 artigos.Discussão e Conclusão: A Endocardite de Válvula protética, classifica-se emEVP precoce (<12 meses pós implantação) e EVP tardia (>12 meses pós implantação)tendo em conta o perfil microbiológico. Staphylococus aureus, é atualmente o agentemais frequente da EVP. No que diz respeito aos mecanismos patogénicos, sabe-se quea maior ocorre no primeiro ano, provavelmente devido à incompleta endotelização daválvula protética neste período. Suspeitar se, clinicamente há febre e um novo ouagravamento de um sopro regurgitante. Diagnóstico de EVP é guiado pelos critérios deDuke modificados, recorrendo-se frequentemente a imagiologia adjuvante com TACe/ou 18F-FDG PET/CT. Abordagem terapêutica é personalizada e inclui cirurgia emdoentes selecionados (insuficiência cardíaca aguda, extensão paravalvular da infeção,deiscência de válvulas, estenose ou regurgitação agravada, embolia recorrente ouinfeção persistente apesar da antibioterapia) e antibioterapia prolongada (mínimo 6meses). Profilaxia antibiótica em procedimentos de risco está recomendada.
Background: Prosthetic heart valve endocarditis is a serious complication ofInfective Endocarditis (IE), affecting 1-6% of individuals with prosthetic heart valves andtranslating into 10-30% of patients with IE. It is associated with severe complications andhigh morbidity and mortality. The approach to PVE needs a fast, objective andmultidisciplinary management plan in order to safeguard the patient avoiding death andassociated severe complications, using antibiotic therapy and surgery frequently.Aim: To provide the reader with an integral perspective of the subject, from itsepidemiology, contextualization, microbiology and associated pathophysiology, typicalclinical presentation, diagnostic and therapeutic approach (with its limitations),prophylaxis of high-risk patients, associated prognosis, and finally the challenges andfuture perspectives.Material and Methods: The PubMed database was searched for articles. Thisstudy covered articles from 1984 to 2020, with an emphasis on articles from the last tenyears, limited to sources in English and French literature.Results: A set of fundamentals was used to restrict the extensive search carriedout, which highlights the key words used, the author of the articles, the date ofpublication, the type of study and methodology applied in them. Thus, after carefullyreading the titles and abstracts of the articles found, 53 articles were selected based onthe principles mentioned above. Discussion and Conclusion: Prosthetic Valve Endocarditis is classified intoearly (<12 months post implantation) and late (>12 months post implantation) PVE takinginto account the microbiological profile. Staphylococcus aureus, is currently the mostfrequent agent of PVE. Regarding pathogenic mechanisms it is known that most occurin the first year, probably due to incomplete endothelialization of the prosthetic valve inthis period. Suspect if clinically there is fever and a new or worsening of a regurgitantmurmur. Diagnosis of PVE is guided by the modified Duke criteria, often using adjuvantimaging with CT and/or 18F-FDG PET/CT. The therapeutic approach is personalizedand includes surgery in selected patients (acute heart failure, paravalvular extension ofinfection, valve dehiscence, aggravated stenosis or regurgitation, recurrent embolism orpersistent infection despite antibiotic therapy) and prolonged antibiotic therapy (minimum6 months). Antibiotic prophylaxis in risky procedures is recommended.

Introdução: As infecções odontogénicas constituem uma das patologias mais prevalentes e o principal motivo para a procura de cuidados médico-dentários a nível mundial. Todos os Médicos Dentistas deverão mostrar-se aptos a realizar um rápido diagnóstico bem como decidir de forma eficaz, ponderada e devidamente fundamentada qual o tratamento a aplicar a cada caso tendo consciência que a progressão de uma infecção odontogénica é, muitas vezes, imprevisível e um tratamento tardio ou incorrecto poderá acarretar complicações que implicam risco de vida para o paciente ao comprometer os espaços faciais profundos da cabeça e pescoço. Objectivo: Esta dissertação pretende, recorrendo à literatura existente, auxiliar o Médico Dentista no diagnóstico de uma infecção odontogénica e, essencialmente, evidenciar qual o tratamento preconizado ou considerado mais eficaz para este tipo de infecções orais. Materiais e métodos: Para a execução desta revisão da literatura, foi desenvolvida uma pesquisa, entre Janeiro e Junho de 2016, recorrendo à Biblioteca Ricardo Reis da Universidade Fernando Pessoa e à Biblioteca da Faculdade de Medicina Dentária da Universidade do Porto, ao portal “DGS” e às bases de dados electrónicas: PUBMED, SCIENCEDIRECT e Repositório Institucional da Universidade de Barcelona utilizando, para esse fim, as “palavras-chave” estabelecidas. Em suma, na realização da presente dissertação, foram consultadas três obras literárias e 23 artigos científicos. Conclusão: Segundo a literatura analisada, não existe consenso absoluto sobre qual o antibiótico que deverá ser prescrito no tratamento de infecções odontogénicas. A amoxicilina continua a ser referenciada como primeira linha de tratamento e, a necessidade e as vantagens da associação desta ao ácido clavulânico, são evidenciadas por diversos autores. A clindamicina é o antibiótico que se apresenta como segunda linha de tratamento, em casos de alergia aos beta-lactâmicos.
Introduction: Odontogenic infections are one of the most prevalent pathologies and the main reason for seeking medical and dental care worldwide. All Dentists should be able to perform a quick diagnosis and decide in an effective, thoughtful and justifiable way which treatment have to apply in each case, being aware that the progression of an odontogenic infection is often unpredictable and a late or incorrect treatment could provoke life risking complications for the patient when compromising deep facial spaces of the head and neck. Objective: This dissertation intends, using existing literature, to assist the Dentist in the diagnosis of an odontogenic infection and, essentially, to find evidence of which is the most recommended treatment or which one is considered the most effective for this type of oral infections. Materials and methods: For the execution of this literature review, a survey was carried out between January and June of 2016, using the Library Ricardo Reis of Fernando Pessoa University and the Library from the Dentistry´s Faculty of the University of Porto, the portal "DGS" and the electronic databases: PUBMED, SCIENCEDIRECT and Institutional Repository of the University of Barcelona using, for this purpose, the keywords established. In sum, in the realization of the present dissertation were queried three literary works and 23 scientific articles. Conclusion: According to the literature review, there is no absolute consensus on which antibiotic should be prescribed in the treatment of odontogenic infections. Amoxicillin is still referred as the first-line treatment and, the necessity and the advantages from the association with clavulanic acid are evidenced by several authors. Clindamycin is presented as the second-line treatment in such cases as allergy to beta-lactams.

碩士
國立屏東科技大學
資訊管理系
92
This thesis paper uses National Health Insurance Research Database of Bureau of National Health Insurance to establish the Decision Support System for Antibiotics Management. It uses the association rule and clustering rule of data mining techniques. With the aid of data mining tool from IBM Intelligent Miner instrument, these data could be digged and analyzed to discover the relationship among the diagnosis, prescription and the common information about antibiotics. The final result will be used as the source of decision knowledge. The main focuses of this research are: (1) Exploring National Health Insurance Research Database to recognize the use of antibiotics in Taiwan , (2) Using different kinds of modules to process the data mining and retrieving. The results could help to find the relationship among the diagnosis, prescription and the common information about antibiotics prescription for the decision knowledge, (3) Using questionnaire and interviewing with doctors and pharmacists to confirm the accuracy of this decision knowledge. Furthermore, the result of web survey will be used to adjust the weight of decision knowledge and feedback to database of antibiotics in order to get more precise decision knowledge, (4) Via different user interfaces, this system could provide the general queries about antibiotics for common users and the supports for doctors to make prescriptions while using antibiotics medicines.

The increased use of antibiotics is considered to be correlated to the increased resistance against antibiotics, hence responsible use is necessary for it to remain efficient and sustainable. To mitigate the resistance, a wide variety of antibiotics should be made available with different Active Pharmaceutical Ingredients (API), providing patients with more aimed cures rather than just few general antibiotics applied for several diseases. A wider range of products requires more effort in maintaining the availability and assuring that antibiotics are always available to be prescribed to patients to buy at their local pharmacies. Facilitating a general availability and minimizing shortages traces back to the procurement process in the supply chain and the relations between involved stakeholders. Pharmaceutical supply chains are highly regulated and monitored by governmental agencies. This thesis aims to explore the procurement process, specifically from the perspective of the pharmacies in Sweden and identify reasons that may cause availability issues and shortage of antibiotics. The research is based on literature review and empirical data collection through interviews with stakeholders in the supply chain. Through cause-and-effect analysis, the reasons behind shortages have been identified, and the pricing model Product of the Period, PoP, has theoretically shown to be the major contributor to the issues. Further research needs to be conducted with a quantitative approach to assess how big of an impact PoP has on the supply chain and antibiotics shortages. The proposed solution is that stakeholders in the supply chain have to start measuring the shortages, specifically for antibiotics.

Projeto de mestrado em Gestão de Unidades de Saúde
No presente trabalho discutimos a Nova Gestão Pública (NGP) e as suas implicações na gestão hospitalar. A revisão de literatura mostra que as reformas passadas vivenciadas no sector são orientadas pela abordagem do NGP. Assim, este modelo de gestão, orientado para os resultados, repercute-se na gestão hospitalar pela procura de melhorias na eficiência e na eficácia da utilização dos recursos públicos. O estudo realizado identifica o caso particular de uma medida recentemente adotada pela gestão hospitalar com o propósito de obtenção de melhoria na qualidade da prescrição médica. Referimonos à adoção, no passado junho de 2010, da ferramenta de stop-orders na prescrição de antibióticos a doentes internados no Centro Hospitalar de Vila Nova de Gaia / Espinho, EPE (CHVNG/E). Assim, a questão de partida orientadora do presente estudo procura relacionar as implicações da adoção desta ferramenta, não só com a qualidade da prestação de cuidados associada, como também com a eficiência da utilização dos recursos ao nível dos consumos de antibióticos em quantidade e valor. Como é reconhecido pela literatura em geral, o consumo de fármacos detém um peso significativo nos gastos totais de um hospital 13,33%, no caso do CHVNGE, sendo que o grupo dos antibióticos detém um peso de 6,85% no total dos fármacos (ano 2010). Assim, o estudo foi realizado com uma amostra de 35.680 registos, que caracterizam o consumo de antibióticos de um total de 19.933 episódios de internamentos verificados entre o período junho de 2009 a julho de 2011. Os testes estatísticos aplicados revelaram diferenças estatisticamente significativas entre o consumo de antibióticos no período anterior e posterior à implementação da medida de melhoria da qualidade na prescrição de fármacos, tendo-se verificado uma diminuição estatisticamente significativa para a média dos consumos médios diários, em quantidade e valor, no período após a implementação da ferramenta de stop-orders. Após uma análise mais analítica dos dados, revelaram-se diferenças significativas na média das quantidades médias diárias de 17 antibióticos (que representam, aproximadamente 60% dos consumos de antibióticos no CHVNG/E), no sentido de redução da quantidade média diária consumida no período posterior à implementação das stop-orders. Por último, o estudo revela que, no período posterior à implementação de stop-orders, verificam-se economias significativas nos gastos com os fármacos antibióticos, sendo que, a introdução das stop-orders justifica parcialmente esta ocorrência.
In this paper we discuss the New Public Management (NPM) and its implications in the hospital management. The literature review shows that the former and experienced reforms in the sector are oriented by the approach of the NPM. So, this management model, results-oriented, reflects itself on the hospital management by looking for improvements in the efficiency and effectiveness of the use of public resources. The study made identifies the particular case of a measure recently adopted by the hospital management with the purpose of obtaining improvement in the quality of the medical prescription. We are referring to the last June 2010 adoption of the stop-orders tool in the prescription of antibiotics to patients admitted to the Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE (CHVNG/E). Thus, the starting point for the guidance of this study tries to relate the implications of the adoption of this tool, not only to the quality care, but also to the efficiency use of the resource in terms of consumption of antibiotics in quantity and value. As it is recognised by the literature in general, the consumption of drugs has a significant weight in the total expenditures of a hospital 13,33%, in the case of CHVNGE, being the group of antibiotics the one which holds a weight of 6,85% in the total of the drugs (year 2010). Therefore, the study was conducted with a sample of 35,680 records, featuring the consumption of antibiotics from a total of 19,933 total admissions recorded episodes between the period of June 2009 and July 2011. The statistical applied tests have revealed differences statistically significant between the consumption of antibiotics in the before and after period to the implementation of the improving quality measure in prescription drugs, with a statistically significant decrease to the average of the daily average consumption in quantity and value, in the period after the implementation of the stop-orders tool. After a more analytical analysis of the data, significant differences are revealed in the average of the daily average quantities of 17 antibiotics (which represent approximately 60% of the consumption of antibiotics in the CHVNG/E), with the purpose of reducing the daily average amount consumed in the period after the implementation of the stop-orders. Finally, the study reveals that, in the period after the implementation of the stop-orders, significant savings are noticed in the expenses spent on antibiotic drugs, as the introduction of the stop-orders would partially justify this occurrence.

Relatório de Trabalho de Projecto apresentado para Cumprimento dos requisitos necessários à obtenção do grau de Mestre em Enfermagem Médico-Cirúrgica
No âmbito do 2º Mestrado em EMC da ESS do IPS que frequentámos era-nos proposto a realização de três estágios e no decorrer dos mesmos a realização de um PIS e um PAC numa Unidade de Saúde de acordo com a metodologia de Projeto com vista à aquisição de competências comuns e específicas do enfermeiro especialista e de Mestre em EMC. Com a realização destes projetos, consideramos ir ao encontro do referido pela Ordem dos Enfermeiros, na tomada de posição sobre segurança do doente, onde refere que a segurança é fulcral à qualidade na saúde e nos cuidados de enfermagem. Refere ainda que algumas medidas como gestão do risco, de segurança ambiental, que englobam uma prática clinica segura, manutenção de um ambiente de cuidados seguros associadas a um corpo de conhecimento científico centrado na segurança da pessoa e nas infra estruturas necessárias para o garantir. (Ordem dos Enfermeiros, 2006) Assim, como produto final do PIS, emergiu um guia farmacológico sobre antibioterapia e um póster com incompatibilidades, diluições e fichas técnicas sobre antibióticos, de forma a dar resposta ao objetivo geral do projeto, ” Melhorar a qualidade e a segurança dos cuidados de enfermagem relacionados com a administração de antibioterapia no serviço de urgência do hospital onde desempenhamos funções.” No que concerne ao PAC desenvolvemos atividades que permitiram a aquisição e consolidação das competências de enfermeiro especialista em enfermagem em pessoa em situação critica. Assim, este relatório pretende traduzir, o trabalho desenvolvido no conjunto dos estágios que permitiu desenvolver competências comuns e específicas do enfermeiro especialista e de mestre em enfermagem médico-cirúrgica.
Within the 2nd Master of EMC ESS IPS we attend us was proposed holding three internships and in the course of the same conducting a PIS and a PAC in a Health Unit in accordance with the Project methodology for the acquisition of common and specific skills of the specialist nurse and Master of EMC. With the completion of these projects, we consider to go out to meet what was said in the position paper on patient safety by the Order of Nurses, which points out that security is central to quality health and nursing care. It also states that some measures such as risk management, environmental security, which include a safe clinical practice, maintaining a safe care environment associated with a body of scientific knowledge focused on the security of the person and the necessary infrastructure to guarantee it. (Order of Nurses, 2006) So, as a final product of PIS, emerged a pharmacological guide on antibiotics and a poster with incompatibilities, dilutions and fact sheets on antibiotics in order to meet the overall objective of the project, "Improving the quality and safety of nursing care related with antibiotic administration in the hospital emergency room where we perform functions. Regarding the PAC we developed activities that enable the acquisition and consolidation skills of the nurse specialist in person in critical situation. Thus, this report aims to translate the work in all the stages that allowed the development of common and specific skills of the nurse specialist and master in medical-surgical nursing.

The purpose of the study was to develop best practice guidelines to prevent permanent hearing loss associated with the management of multi-drug resistant tuberculosis (MDR-TB) through raised awareness and monitoring. The Human Immunodeficiency Virus (HIV) and MDR-TB are global public health problems requiring urgent scale-up of treatment services. Irreversible sensorineural hearing loss (SNHL) is one of the adverse drug reactions of the current World Health Organization (WHO) recommended MDR-TB chemotherapy fuelling another public health problem, that disabling hearing loss, which is the second highest contributor of Years Lived with Disability (YLD) according to the World Health Report (2003). Expansion of MDR-TB treatment threatens to increase incidence of SNHL unless there is urgent implementation of intervention towards preservation of hearing for patients on treatment. This empirical study determined and documented the incidence of SNHL in HIV positive and HIV negative patients on MDR-TB treatment, the risk factors for SNHL, from the time treatment initiation to SNHL. Based on the findings, developed and improved the understanding of best practice guidelines for monitoring and prevention of MDR-TB treatment-related SNHL. The empirical study recruited a cohort of 173 patients with normal hearing status, after diagnosis with MDR-TB and enrolled on MDR-TB therapy over thirteen month period. Patients in the cohort received monthly hearing sensitivity testing during the intensive MDR-TB therapy when injectable aminoglycoside antibiotics are part of the treatment regimen. The three study endpoints included completion of the eight-month intensive treatment phase without developing hearing loss, development incident hearing loss or loss to follow up. Data was analysed using STATA statistical software and summarised using frequencies, means, proportions, and rates. The study documented incidence of SNHL, time to hearing loss and risk factors for hearing loss. Recommendations to prevent and monitor hearing loss are made based on the the study findings.
Health Studies
D. Litt. et Phil. (Health Studies)