La maitrise de la résistance bactérienne et l’utilisation prudente des antibiotiques à l’hôpital constituent des enjeux majeurs pour les autorités de santé dans tous les pays européens. Toutefois, les connaissances en matière de consommation des antibiotiques et de politique de bon usage des antibiotiques dans les établissements sont limitées. Dans ce contexte, le travail de cette thèse permet de donner une meilleure vision de la consommation des antibiotiques dans les pays européens à partir des données de surveillance disponibles. Il apporte également des cibles d’amélioration de la prescription des antibiotiques et identifie plusieurs indicateurs de qualité pour mener à bien une politique de bon usage des antibiotiques. De plus, ce travail utilise le modèle des hôpitaux français pour identifier des critères d’ajustement de la consommation des antibiotiques facilement disponibles qui sont essentiels à mettre en œuvre pour établir des comparaisons entre les différents hôpitaux. Il s’intéresse également à la relation entre la politique de bon usage des antibiotiques dans les hôpitaux et une moindre consommation des antibiotiques. En conclusion, les données de surveillance de la consommation des antibiotiques ont donc permis de répondre à plusieurs hypothèses de recherche et de dégager de nouveaux axes de réflexions. / The control of bacterial resistance and the prudent use of antibiotics in hospitals are major challenges for health authorities in all European countries. However, little is known regarding antibiotic consumption and antibiotic policies in hospitals. In this context, this thesis provides insight into the antibiotic consumption using available survey databases. It also identifies targets for quality improvement and several quality indicators which are essencial to carry out a prudent use antibiotic policy. Moreover, the model of French hospitals was used to explore easily available adjustment criteria for the antibiotic consumption which are crucial to implement comparisons between different types of hospitals. This work brings light onto the relationship between the antibiotic policy and a low level of antibiotic use in French hospitals. In conclusion, survey databases have enabled us to answer several research assumptions and to generate new horizons of reflection.

This diploma thesis deals with resistance of microorganisms to antibiotics and public awareness of this topic. The aim of the thesis was to find out what the public awareness of the given topic is and what knowledge the public has about the possibilities of prevention of creation and spreading of resistant microorganisms. Three main hypotheses have been set: Hypothesis 1: The public has no deeper knowledge of antibiotic treatment. Hypothesis 2: The public will in most cases get information on antibiotic treatment from a doctor. Hypothesis 3: Most people are unaware that they can contribute by rational use of antibiotics to prevent antibiotic resistance. In order to achieve the stated goals of the diploma thesis, a quantitative method of research was used. Data collection was conducted through anonymous questionnaire survey of the public population using the Click4Survey.cz web server and distribution of paper questionnaires in FN Plzeň. Results of the questionnaire survey were evaluated based on statistical data processing in Microsoft Office Excel 2007, and a Chi-squared test of independence in the pivot table and a relative frequency test were used to verify the hypotheses. Based on the evaluation of the results, it was found that among the groups of respondents, depending on whether they filled in a questionnaire on the Internet or a printed questionnaire at the hospital, there are fundamental statistical differences in knowledge and awareness of the problem. That is why it was necessary to further evaluate these two groups separately. Antibiotic resistance nowadays is a very important medical issue. The main cause is inconsistent use or overuse of antibiotics in both human and veterinary medicine, as well as insufficient awareness of the extent of the problem and the consequences of antibiotic resistance. For this reason, I have chosen this issue as a topic for my diploma thesis to highlight the risks of antibiotic resistance and to provide information primarily to the general public.

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.

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.

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.

[Truncated abstract] The prinicipal aim of this thesis was to explore the relationship between 3rd generation cephalosporin antibiotics and hospital-acquired Clostridium difficile-associated diarrhoea (CDAD). This antibiotic class has been implicated in the aetiology of CDAD; therefore restriction of these antibiotics via antibiotic policies represents a potential strategy for prevention and control of CDAD. Successful control of CDAD in hospitals translates to improved quality of care for patients, and a reduction of pressure on hospital resources. Therefore, the objectives of this study were to determine whether 3rd generation cephalosporins were related to CDAD, to evaluate the effect of changes to antibiotic policy on the incidence of CDAD, and to determine the impact of CDAD on patient length of stay and hospital costs. The study was conducted in Sir Charles Gairdner Hospital (SCGH), a public teaching hospital located in Perth, the capital city of the state of Western Australia. Evidence for an association between 3rd generation cephalosporins and CDAD was obtained from studies of ecologic- and individual-level data. A time series analysis of the relationship between monthly consumption of 3rd generation cephalosporins and the incidence of CDAD in SCGH was undertaken covering the period 1994 to 2000. The results demonstrated a positive relationship between the use of 3rd generation cephalosporins and CDAD. A matched case-control study that involved 193 adult inpatients diagnosed with CDAD and 386 adult inpatients without CDAD, selected from the period 1996 to 2000, was conducted. Information was collected on exposure to 3rd generation cephalosporin antibiotics during hospitalisation, as well as exposure to other antibiotics and medications, procedures, and comorbidities. Results from conditional logistic regression analyses found CDAD cases were six times more likely to be exposed to 3rd generation cephalosporins during their admission, prior to the onset of diarrhoea, than controls (adjusted odds ratio [OR] = 6.17, 95% confidence interval [CI] = 1.56-24.37). Approximately one third of CDAD in the study population could be attributed to 3rd generation cephalosporins. CDAD cases were also four times more likely to have been exposed to either amoxicillin-clavulanate or ticarcillin-clavulanate (adjusted OR=4.23, 95% CI=1.81-9.93). In October 1998, an antibiotic policy was introduced at SCGH that restricted the use of ceftriaxone, the 3rd generation cephalosporin most commonly used by the hospital. During 1999 and 2000, the incidence of CDAD halved as ceftriaxone consumption fell in response to this policy. The effect of this policy was demonstrated in the time series model; during the post-policy period the relationship between ceftriaxone and CDAD that was evident prior to the policy was cancelled out. From the individual-level data, obtained from the case-control study, a reduction in the prevalence of exposure to 3rd generation cephalosporins from 11% to 1% accounted for a 30% reduction in the incidence of CDAD. Data from the case-control study was also used to analyse the independent contribution of CDAD to length of stay and admission costs using multiple linear regression