As infecções relacionadas à assistência à saúde (IRAS) são um grave problema de saúde pública cujo prognóstico tem sido desfavorecido pela emergência e endemicidade de bactérias multirresistentes (MRs). Neste cenário, seguindo uma tendência mundial, no Brasil, infecções por cepas de Acinetobacter baumannii MRs produtoras de carbapenemases do tipo OXA são atualmente consideradas uma emergência clínica e epidemiológica. Na falta de alternativas terapêuticas efetivas para infecções relacionadas, este trabalho objetivou avaliar efeitos sinérgicos (utilizando checkerboard e time-kill) decorrentes da combinação de 10 antimicrobianos de diferentes classes, contra 8 cepas MRs de A. baumannii, clonalmente não relacionadas, produtoras de carbapenemases do tipo OXA-23, OXA-72, OXA-58 e OXA-143, representativas de diferentes centros hospitalares do Brasil. Como resultado, a combinação amicacina/tigeciclina apresentou atividade sinérgica (S= ΣCIF ≤ 0,5) e parcialmente sinérgica (PS= &#931CIF ;0,5-0,75) contra 4 (50%) cepas produtoras de OXA-143 ou OXA-72, e 2 cepas (25%) produtoras de OXA-23, respectivamente. Por outro lado, a combinação polimixina B/imipenem apresentou atividade S e PS contra 3 (37,5%) isolados OXA-143, OXA-23 ou OXA-72 positivos, e 1 (12,5%) isolado produtor de OXA-58, respectivamente. Já, a combinação amicacina/ampicilina-sulbactam foi S contra 2 (25%) A. baumannii OXA-143 ou OXA-23 positivos, sendo PS contra dois (25%) A. baumannii OXA-58 ou OXA-143/23 positivos. De interesse, foi o efeito S da combinação polimixina B/vancomicina, contra 2 cepas (25%) produtoras de OXA-72 ou OXA-23. Por outro lado, a combinação ampicilina-sulbactam/rifampicina apresentou atividade PS contra 6 (75%) cepas produtoras das variantes OXA-23, OXA-143, OXA-72 ou OXA-58. Da mesma forma, rifampicina combinada com polimixina B foi sinérgica para uma cepa OXA-23 (12,5%) e PS para 5/8 (62,5%) cepas produtoras de OXA-72, OXA-58, OXA-23/-OXA143 ou OXA-143. O efeito sinérgico da combinação polimixina B/imipenem foi confirmado, in vivo, no modelo murino de infecção, tanto por avaliação histopatológica como por redução das UFC/g pulmão ou baço (p ≤ 0,05). Finalmente, foi avaliada a atividade, in vitro, do lípide catiônico brometo de dioctadecildimetilamônio (DDA), individualmente e em combinação com tigeciclina. DDA possui efeito bactericida, e potencializou sinergicamente a tigeciclina contra 2 (25%) cepas OXA-143 ou OXA-23 positivas. A atividade do DDA, assim como a atividade da sua combinação com tigeciclina foram efetivas já na segunda hora de interação, como avaliado pelas curvas de morte. Em resumo, o efeito sinérgico decorrente do uso combinado de amicacina, tigeciclina, polimixina B, imipenem, rifampicina ou ampicilina/sulbactam, pode constituir uma alternativa terapêutica para o tratamento de infecções produzidas por cepas de A. baumannii MRs produtoras de oxacilinases, sendo que nanofragmentos catiônicos de bicamada do lipídeo sintético de DDA tem potencial para consolidar um produto de aplicação clínica. / Healthcare-associated infections (HAIs) are a serious public health issue, which have been related with an unfavorable prognosis due to the emergence and endemicity of multidrug-resistant (MDR) bacteria. In this scenario, following a worldwide trend, in Brazil, infections produced by MDR OXA-type carbapenemase-producing Acinetobacter baumannii are currently considered a clinical and epidemiological urgency. In the absence of effective therapeutic alternatives for related infections, this study aimed to evaluate synergistic effects (by using time-kill and checkerboard assays) achieved by the combination of 10 different classes of antimicrobial against 8 strains of MDR, clonally unrelated, A. baumannii strains producing OXA-23, OXA-72, OXA-58 and OXA-143 carbapenemases, being representatives of different medical centers in Brazil. As a result, the combination of amikacin / tigecycline showed synergistic (S = ΣFIC ≤ 0.5) and partially synergistic (PS = 0.5 to 0.75 ΣFIC) activity against 4 (50%) OXA-72 or OXA-143 producing A. baumannii strains, and two strains (25%) producing OXA-23, respectively. Moreover, the combination of polymyxin B / imipenem showed S and PS activity against 3 (37.5%) OXA-143, OXA-23 and OXA-72 positive isolates, and 1 (12.5%) OXA-58 producer, respectively. On the other hand, the combination amikacin / ampicillin-sulbactam was S against 2 (25%) OXA-143 and OXA-23 positive strains, being PS against two (25%) OXA-58- and OXA-143/23-producing A. baumannii. Of interest was the synergistic effect achieved by polymyxin B plus vancomycin against two strains (25%) producing OXA-72 and OXA-23, respectively. Furthermore, the ampicilina-sulbactam / rifampicin combination displayed a PS activity against six (75%) strains producing OXA-23, OXA-143, OXA-72 or OXA-58-type enzymes. Likewise, rifampicin combined with polymyxin B was S against 1 (25%) OXA-23-positive A. baumannii being PS to 5/8 (62.5%) strains producing OXA-72, OXA-58, OXA-23/-OXA143 or OXA-143. The synergistic effect of the combination polymyxin B / imipenem was confirmed, in vivo, in the murine model of infection, by using both histopathological studies and bacterial clearance from the lungs and spleen (CFU/g, p≤ 0.05). Finally, we evaluated the in vitro activity of the cationic lipid dioctadecyldimethylammonium bromide (DDA), alone and in combination with tigecycline. DDA display a bactericidal effect, enhancing synergistically the activity of tigecycline against 2 (25%) OXA-143 and OXA-23 positive strains, respectively. DDA activity alone and in combination with tigecycline was effective on the second hour of interaction, as evaluated by time-kill assays. In summary, the synergistic effect resulting from the combined use of amikacin, tigecycline, polymyxin B, imipenem, rifampicin or ampicillin / sulbactam, could be an alternative therapy for the treatment of infections caused by MDR A. baumannii strains producing oxacilinases. On the other hand, cationic bilayer nanofragments of DDA has potential for consolidating a product for medical application.

Introduktion: En god handhygien utgör grunden för att minska smittspridning av smittsamma sjukdomar. Vårdrelaterade infektioner kostar samhället mycket rent ekonomiskt och i lidande för den enskilde. Individer med funktionsnedsättning som bor på gruppbostad riskerar att drabbas om inte vårdpersonalen tillämpar de basala hygienrutinerna och är relevant ur ett folkhälsovetenskapligt perspektiv. Syfte: Att analysera en befintlig självskattningsenkät avseende efterlevnad av basala hygienrutiner gällande handhygien som genomförts under våren samt hösten 2020 bland kommunanställd omvårdnadspersonal på gruppboenden inom en kommun i Stockholm. Metod: En upprepad tvärsnittsstudie med kvantitativ och kvalitativ analys av en befintlig självskattningsenkät. Analysen baseras på enkätsvar med en svarsfrekvens på 78 % från personal inom kommunens 15 gruppboenden och bestod av 80 deltagare på våren respektive 81 deltagare på hösten2020. Resultat: Mellan 69 - 97,5 % av deltagarna ansåg att de följde hygienrutinerna avseende basal handhygien under år 2020. I jämförelse mellan vår och höst sågs en signifikant förbättring av användning av handsprit före omvårdnadsmoment. I studiens kvalitativa del framkom deltagarnasupplevelse av hinder i tillämpningen och dessa utgjordes bland annat av; varierad användning av handskar, ovetskap, glömska, tidsbrist, tillgänglighet samt praktiska hinder i verksamheten. Slutsats: En stor del av omvårdnadspersonalen ansåg att de följde de basala hygienrutinerna avseende handhygien men kravet på att all personal skall arbeta efter hygienrutinerna avseende handhygienuppfylls inte. Hygienutbildningen som omvårdnadspersonalen erbjuds behöver utvecklas för att främja utveckling av health literacy vilket kan bidra till en ökad förståelse för varför tillämpningen är viktig. Detta kan förbättra följsamheten till de basala hygienrutinerna. / Introduction: Good hand hygiene is the basis for reducing the spread of infections. Healthcare-related infections cost society a great deal financially and in suffering for the individual. Individuals with disabilities who live in group housing are at risk if the care staff does not apply the basic hygiene routines. Aim: Analyze an existing self-assessment survey regarding compliance with basic hygiene routines regarding hand hygiene that was carried out during the spring and autumn of 2020 among municipally employed nursing staff in group housing. Method: A repeated cross-sectional study with quantitative and qualitative analysis of an existing self-assessment survey. The analysis is based on questionnaire responses from staff with a response rate of 78%, within the municipality's 15 group homes and consisted of 80 participants in the spring and 81 participants in the autumn of 2020. Results: Between 69-97.5% of the participants considered that they followed the hygiene routines regarding basic hand hygiene during the year 2020. In a comparison between spring and autumn, a significant improvement was seen in the use of hand alcohol before nursing. The qualitative part of the study also revealed the participants' experience of obstacles, and included use of gloves, ignorance, forgetfulness, lack of time, accessibility and practical obstacles. Conclusion: A large part of the nursing staff believed that they followed the basic hygiene routines regarding hand hygiene. The hygiene training offered by the nursing staff needs to be developed to promote the development of health literacy. This can improve compliance with the basic hygiene routines.

Les infections associées aux soins de santé ou infections nosocomiales (IN) sont des effets indésirables ayant de graves conséquences sur la santé des patients. Les pathogènes responsables de certaines IN sont transmis par le biais des mains contaminées, entre autres celles des professionnels de la santé (PS). Ces IN sont donc en théorie évitables. L’hygiène des mains (HDM) est considérée comme la pierre angulaire de la prévention et contrôle des infections (PCI). C’est un moyen simple, efficace et peu couteux qui permet d’empêcher la transmission des pathogènes et de réduire la probabilité d’infections ultérieures. Malheureusement, les taux de conformité à l’HDM au sein des PS restent inférieurs à la cible globale de 80% indiquée par l’OMS, malgré de nombreuses campagnes instaurées pour sensibiliser ceux-ci. Considérant les faibles taux de conformité à l’HDM, les autorités sanitaires envisagent d’augmenter cette cible. Le but de mon mémoire est de synthétiser les preuves existantes sur l’association entre le taux de conformité à l’HDM et les taux d’incidence des IN. Ceci permettrait de déterminer s’il y a un taux optimal de conformité à l’HDM qui serait associé au plus faible taux d’incidence des IN. Les résultats obtenus permettront aux autorités sanitaires de considérer la pertinence de viser des cibles d’HDM plus élevées. J’ai effectué une revue systématique de la littérature afin d’analyser les données disponibles sur l’association des taux de conformité à l’HDM et le taux d’incidence des IN. J’ai également analysé les données sur les taux de conformité à l’HDM et les taux d’incidence d’IN des installations de soins de santé du Québec. Les résultats semblent démontrer qu’au-delà d’un taux de conformité à l’HDM de 60%, il y a peu de différence apparente entre un fort taux de conformité à l’HDM et un faible taux d’incidence des IN. L’HDM, quoique mesure très importante, n’est pas le seul facteur servant à réduire les IN. / Healthcare-associated infections (HAIs) are an adverse event with serious consequences on the patients’ health. The pathogens responsible for some HAIs are mainly transmitted through hands, including those of healthcare workers (HCW). These HAIs are therefore theoretically preventable. Hand hygiene (HH) is considered the cornerstone of infection prevention and control. It is a simple, effective, and inexpensive way to prevent the transmission of pathogens and reduce the likelihood of subsequent infections. Unfortunately, HH compliance rates remain suboptimal among HCWs despite numerous HH campaigns. Considering the low HH compliance rates among HCWs, health authorities are considering further increasing the target for HH compliance rates. The goal of my dissertation is to synthesize the current evidence on the association between HH compliance rates and the incidence rates of HAIs to determine if there is an optimal HH compliance rate that is associated with the lowest incidence rate of HAIs. This will provide health authorities intel, to consider the relevance of setting higher HH compliance targets. I performed a systematic review of the literature to analyze the available data on the association of HH compliance rates and HAI incidence rates. I also analyzed HH compliance rates and HAI incidence rates reported by healthcare facilities in the province of Québec. The results seem to show that beyond a HH compliance rate of 60%, there are no clear differences between higher HHC rates and low incidence rates of HAIs. Although very important, HH compliance is not the only factor contributing to the decrease of HAIs.

Introduktion: Vårdrelaterade infektioner (VRI), är ett hot mot folkhälsan på nationell och global nivå på grund av den belastning de anbringar drabbade patienter, anhöriga, sjukvårdssystemens samtliga delar samt späder på utvecklingen av antimikrobiell resistens genom att ofta behöva behandlas med antibiotika. VRI förebyggs genom vårdhygieniska hänsyn på vårdens samtliga beslutsfattande och utförande nivåer, samt genom att patienter och närstående möjliggörs medverkan. Patientmedverkan i att förebygga VRI är ett underanvänt och understuderat område där sjuksköterskor, i sin expertisroll inom omvårdnad i partnerskap med patienten, har möjlighet att spela en framträdande roll. Syfte: Syftet var att undersöka sjuksköterskors attityder till patientmedverkan i att förebygga VRI. Metod: Datainsamling skedde genom semistrukturerade individuella intervjuer med åtta sjuksköterskor i somatisk slutenvård. Analysmetod var kvalitativ innehållsanalys med induktiv ansats. Resultat: Elva underkategorier, tre kategorier och ett övergripande tema framkom. Kategorierna var ”Positivt med patientmedverkan”, ”Vården behöver bjuda upp” och ”Patienten behöver med på banan”. Det övergripande temat var ”Viktigt område, beroende av partnerskapet mellan vårdgivare och patient, i behov av utveckling och konkretisering”. Slutsats: Sjuksköterskors attityder till patientmedverkan i att förebygga VRI inbegriper att VRI representerar ett reellt, närvarande hälsohot som tas på största allvar. Patientens medverkan i att förebygga VRI upplevdes som ett positivt och potentiellt vinstgivande fenomen, beroende av partnerskapet mellan vårdgivare och patient. Området är i behov av att uppmärksammas, konkretiseras och utvecklas för att kunna vara en självklar del i personcentrerad och jämlik hälso- och sjukvård. / Introduction: Healthcare associated infections (HAI), are a threat to public health, both nationally and globally, due to the burden of affected patients, relatives, various parts of the healthcare system and the increasing effect it has on antimicrobial resistance, as HAI often require antibiotic treatment. HAIs are prevented by infection-prevention and control on all levels of the healthcare system including participating patients and relatives. Patient-participation in the prevention of HAI is an underused and underexplored area, where registered nurses can play a vital role as an expert in nursing care in so called partnership with the patient. Aim: The aim was to explore attitudes among nurses towards patient-participation in the prevention of HAI. Methods: Data collection was made by semistructured individual interviews with eight registered nurses, working in hospital inpatient care. The method for analysis was qualitative content analysis with an inductive approach. Results: Eleven subcategories, three categories and one all-embracing theme emerged. The categories were ”Patient-participation is positive”, ”The healthcare-system needs to invite patients” and ”Patients needs to come onboard”. The theme was ”Important topic, depending on the partnership caregiver-patient, in need of development and to be concretizised.” Conclusion: The attitudes among nurses towards patient-participation in preventing HAI includes that HAI represents a serious, real and present health-threath. Patient-participation in the prevention of HAI was perceived as a positive and potentially gainful phenomenon, depending on the caregiver-patient partnership. The topic needs to be noticed, concretized and elaborated in order to become a self-evident part of a person-centered, equal healthcare.

Background: Healthcare workers’ hand hygiene remains a key pillar because it prevents and controls healthcare associated infections. Healthcare Workers’ hand hygiene compliance is suboptimal. Aim: The study developed contextualised guidelines for Healthcare Workers’ hand hygiene and infection control in patient care. Methods: The Precede-Proceed model with Theory of Planned Behaviour guided the study. The study was conducted following the mixed methodology approach, observational survey, exploratory, descriptive and contextual in nature study with mixed thematic analyses in a research wheel process. Data were collected through direct participant observation of hand hygiene opportunities through observing (n=95 Healthcare Workers; n=570 practices). Self-administered questionnaires were used to collect data from Healthcare workers (n=189) regarding challenges they faced in achieving hand hygiene. Structured interviews were conducted with patients (n=574). Retrospective reviews of healthcare associated infections and their associated mortalities were carried out from mortality records. Data were analysed retrospectively. Partly the data were statistically and mixed thematically analysed. Guidelines were developed using intervention alignment throughout, mapping, matching, pooling, patching and validation corroborated with Precede-Proceed models’ best practices. The study was ethically reviewed and approved by University of South Africa and the Medical Research Council of Zimbabwe project numbers, 6067662 and MRCZ/B/208. Results: Hand hygiene non-compliances were mostly found in the following contexts, after touching patients’ surroundings, and before doing an aseptic procedure. A non-hand hygiene compliance of Healthcare workers 167(29.3%) and compliance 403(70.7%) in context was suboptimal with sad patients and challenges faced by Healthcare workers. Conclusion: Healthcare Workers had gaps in hand hygiene compliance and availability of required resources. Gaps were also noted in ongoing hand hygiene promotion educational strategies and guidelines to comply and prevent. Guidelines to enhance hand hygiene included, attend to hand hygiene strictly after touching patient surroundings, bed linen, lockers and curtains to prevent gastroenteritis; follow standard precautions against HCAIs from spreading to patients' environments; and comply with hand hygiene guidelines, policies and regulations for best practice with patients. The study contributes generalisable knowledge. / Health Studies / D. Litt et Phil. (Health Studies)

The literature directly comparing the epidemiology of MRSA among adult and pediatric hospitalized patients is strikingly minimal. The objective of this thesis was to identify any differences between these two patient groups. The Canadian Nosocomial Infections Surveillance Program MRSA data (1995 to 2007: n=1,262 pediatric and 35,907 adult cases) were used to compare MRSA clinical and molecular characteristics and rates. Hospital characteristics were modeled using repeated measures Poisson regressions. The molecular and epidemiological characteristics of MRSA differed significantly between adults and children. Compared to children, MRSA in adults was more likely to be healthcare-associated, colonization, SCCmec type II, PVL negative, and resistant to most antibiotics. Rates of MRSA in Canada increased in both populations over time but were significantly higher in adults. The hospital characteristics associated with increased MRSA rates differed in adult and pediatric facilities. Implications for infection prevention and control strategies are discussed.

The literature directly comparing the epidemiology of MRSA among adult and pediatric hospitalized patients is strikingly minimal. The objective of this thesis was to identify any differences between these two patient groups. The Canadian Nosocomial Infections Surveillance Program MRSA data (1995 to 2007: n=1,262 pediatric and 35,907 adult cases) were used to compare MRSA clinical and molecular characteristics and rates. Hospital characteristics were modeled using repeated measures Poisson regressions. The molecular and epidemiological characteristics of MRSA differed significantly between adults and children. Compared to children, MRSA in adults was more likely to be healthcare-associated, colonization, SCCmec type II, PVL negative, and resistant to most antibiotics. Rates of MRSA in Canada increased in both populations over time but were significantly higher in adults. The hospital characteristics associated with increased MRSA rates differed in adult and pediatric facilities. Implications for infection prevention and control strategies are discussed.