Treatment failure in community-acquired pneumonia (CAP) is the failure to normalize the clinical features (eg, fever, cough, sputum production), or nonresolving image in chest radiograph, despite antimicrobial therapy. The incidence of treatment failure in CAP has not been clearly established; according to several studies it ranges between 6% and 15%. The rate of mortality increases significantly, especially in those patients with severe CAP. It is important to be able to identify what patients are at risk for progressive or treatment failure pneumonia that may make them candidates for a more careful monitoring. This doctoral thesis has been structured following the guidelines of the rules for submission of doctoral theses as a compendium of publications, adopted by the Council, Department of Medicine, University of Barcelona. The studies are part of this thesis belong to the same line of research, validated the current guidelines of pneumonia-community acquired and hospital acquired. The results of the studies have provided relevant and innovative in this field and were collected in 2 original articles published in international journals with a widespread global impact factor of 16,37 points.

This dissertation deals with three problems in health care. In the first, we consider the incentives to change prices and capital levels at hospitals, using optimal control under the assumption that private payers charge higher prices if patients consume more hospital services. The main results are that even with fixed technology, investment and prices exhibit explosive growth, and that prices and capital stock grow in proportion to one another. In the second chapter, we study the flow of nosocomial infections in an intensive care unit. We use data from Cook County Hospital, along with numerous results from the literature, to construct a discrete event simulation. This model highlights emergent properties from treating the flow of patients and pathogens in one interconnected system, and sheds light on how nosocomial infections relate to hospital costs. We find that the system is not decomposable to individual systems, exhibiting behavior that would be difficult to explain in isolation. In the third chapter, we analyze a proposed change in diversion policies at hospitals, in order to increase the number of patients served, without an increase in resources. Overcrowding in hospital emergency departments is caused in part by the inability to send patients to main hospital wards, due to limited capacity. When a hospital is completely full, the hospital often goes on ambulance diversion, until some spare capacity has opened up. Diversion is costly, and often leads to waves of diversions in systems of hospitals, a situation that is regarded as highly problematic in public health. We construct and analyze a continuous-time Markov chain model for one hospital. The intuition behind the model is that load-balancing between various hospitals in a metro area may hinder full congestion. We find that a more flexible contract may benefit all parties, through the partial diversion of federally insured patients, when a hospital is very close to full. Discrete event simulation models are run to assess the effect, using data from DeKalb Medical Center, and also to show that in a two-hospital system, more federally insured patients are served using this mechanism.

Gram-negative infection has been linked to hospital water although few studies have examined whether water systems are reservoirs of nosocomial pathogens. This study investigated longitudinal recovery of the opportunistic pathogens Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii from water outlets of a haematology unit and evaluated Point-Of-Use Filtration (POU-F) as a control measure. In a two-year double cross-over trial, water samples and swabs were taken weekly from 39 showers/taps on the unit. Four study phases alternated between non-filtered (Phases 1 & 3), and filtered outlets (Phases 2 & 4) using Pall AquasafeTM 14-day filters. In Phases 1 & 3; 99% of 1396 samples yielded bacterial growth, with colonies generally too numerous to count. Target species were isolated from 22% of water samples (P. aeruginosa 14%; S. maltophilia 10%) and 10% of swabs. P. aeruginosa was particularly associated with handwash stations and S. maltophilia with showers. A. baumannii was not isolated. With POU-F; 22% of 1242 samples yielded bacterial growth (mean CFU/100ml ,4.6). S. maltophilia was isolated only once from water but never from outlet swabs. PCR typing identified clusters of isolates colonizing different outlets over time but no clear association between water and patient isolates was identified. The incidence of Gram negative infections remained low throughout the study. Without POU-F, water from taps/showers represented a source of bacteria including the target species. POU-F substantially reduced the frequency and number of target species from every outlet, and merits further investigation as an intervention to protect immunocompromised patients from opportunistic pathogens.

The study arose out of a need to investigate and control a nosocomial outbreak caused by multidrug resistant Acinetobacter spp in the fifteen-bed intensive care unit of King Edward VIII Hospital. Following the discovery of the index case, four other patients were found to have a similar strain of Acinetobacter spp. All fifteen patients in the ward were subsequently screened for the organism. Forty-seven isolates were obtained from 12 patients. Eight of the patients were infected with the organism and six of these eight patients subsequently died. Swabs from the ward environment were also screened for the organism, which was found in patients' baths, suction water and urine collection jars. The outbreak was aborted by the use of strict infection control techniques. Minimum inhibitory concentrations (MICs) of 20 of the 47 isolates were determined for the following antimicrobials: imipenem, ciprofloxacin, gentamicin, amikacin, netilmycin,cefotaxime, ceftazidime and tetracycline. The same 20 isolates were further typed using ribotyping. Seven different antibiogram patterns were obtained using the MIC data. The majority of isolates (11) fit into a Single type, and showed resistance to all drugs tested, except for susceptibility to tetracycline and netilmycin only. Ribotyping revealed 5 different types. There were 9 isolates of ribotype a, 2 of ribotype b, 3 of ribotype c, 5 of ribotype d and 1 of ribotype e. In conclusion, this study describes a nosocomial outbreak with a multidrug resistant Acinetobacter spp. in an intensive care unit. The results showed that there was no correlation between the two typing methods used, ribotyping was more discriminatory than antibiogram types, with the majority of strains belonging to two different ribotypes. / Thesis (M.Med.)-University of Natal, Durban, 2000.

Ziel: Ziel dieser Studie war es, Risikofaktoren für operationsbezogene postoperative Infektionen (SSIs) nach spinalen Eingriffen zu identifizieren und die Wirksamkeit einer perioperativen Antibiotikaprophylaxe zur Vermeidung von Infektionen zu ermitteln. Methoden: Von Januar 2002 bis März 2004 erfolgte eine retrospektive Analyse neurochirurgischer Eingriffe unter dem Ausschluss kranieller Operationen. Untersuchte Risikofaktoren waren dabei Diagnose und Art der Operation sowie Höhe des Eingriffs an der Wirbelsäule, Alter und Geschlecht, Operationsdauer, postoperative Krankenhausliegedauer (LOS) und verlängerter Aufenthalt auf der Intensivstation (ITS). Weiterhin wurden die Wirksamkeit und der Umgang mit einer perioperativen Antibiotikaprophylaxe beobachtet. Die Infektionsrate von SSIs und anderen postoperativen Nosokomialinfektionen stellte das ausschlaggebende Kriterium dafür dar, dass ein Risikofaktor als solcher definiert wurde. Ergebnisse: Die Gesamtinfektionsrate von SSIs lag bei 2,29% (34 von 1484). Parallel zu der Komplexität der Operationen wurden zunehmende Infektionsraten festgestellt: Bandscheibenvorfall (3,48%), Spinalkanalstenose (3,97%), spinales Trauma (4,55%), spinaler Tumor (12,5%). Wesentliche Risikofaktoren waren dabei Operationsdauer (> 2 Stunden), LOS (> 7 Tage), Aufenthalt auf der Intensivstation (> 48 Stunden). Das Alter bei spinalen Eingriffen wurde auch, im Gegensatz zu Geschlecht und der Eingriffshöhe an der Wirbelsäule, als ein Risikofaktor gewertet. Bei Anwendung einer perioperativen Antibiotikaprophylaxe erhöhte sich die Infektionsrate (1,35% auf 6,06%; p <0,01). Der Einsatz einer perioperativen Antibiotikaprophylaxe wurde mit komplexeren Operationen, beispielsweise Eingriffen bei spinalen Tumoren, mit Eingriffen bei jüngeren (≤30 Jahre) oder älteren (>60 Jahre) Patienten, mit Eingriffen mit hohen Infektionsraten und mit Eingriffen mit Risikofaktoren (Operationsdauer, LOS, ITS) verbunden. Mit einem kurzen (≤24 Stunden) Protokoll der Prophylaxe im Vergleich zu einem längeren (>24 Stunden)zeigten sich niedrigere Infektionsraten (2,5% gegenüber 10%, p = 0.006). Die Antibiotikaprophylaxe erfolgte größtenteils mit Cefazolin (76,47%) und es wurden überwiegend grampositive Mikroorganismen, Haupterreger Staphylococcus aureus, isoliert. Eine Verschiebung des Verhältnis zugunsten der gramnegativen und zu Lasten der grampositiven Erreger zeigte sich bei Eingriffen mit ITS Aufenthalt, bei Eingriffen mit Durchführung einer perioperativen Antibiotikaprophylaxe und in Kombination mit postoperativen Allgemeininfektionen. Abgesehen von den Eingriffen mit Aufenthalt auf ITS, stellten die grampositiven Erreger zahlenmäßig weiterhin die dominanten Erreger dar. Schlussfolgerung: Risikofaktoren in der spinalen Chirurgie wurden identifiziert und deren Berücksichtigung hilft SSIs und deren Komplikationen zu verhindern. Es gab kein Anzeichen dafür, dass eine perioperative Antibiotikaprophylaxe SSIs reduziert. Eine Prophylaxe wurde auf komplexere Operationen mit einem höheren Risikoprofil limitiert und sollte einem kurzen Anwendungsprotokoll folgen. Im Zusammenhang mit der zunehmenden Anzahl komplexer chirurgischer Verfahren mit steigenden Infektionsraten bei gleichzeitig wachsender Resistenzentwicklung muss die Rolle der perioperativen Antibiotikaprophylaxe kritisch gesehen werden und sollte weiterführend untersucht werden.

P. aeruginosa est l'un des principaux pathogènes responsables d'infections nosocomiales. Les infections aiguës à cette bactérie sont associées à une morbidité et une mortalité élevées, notamment lorsque ces bactéries envahissent le système sanguin. Dans la majorité des cas, ces infections du sang sont la conséquence du franchissement par P. aeruginosa de deux barrières tissulaires: l'épithélium pour les muqueuses et l'endothélium pour les vaisseaux. Bien que ces évènements soient des étapes cruciales de la dissémination systémique des bactéries, les mécanismes permettant la pénétration du pathogène dans l'organisme sont à ce jour mal compris. Pour l'endothélium, nous démontrons que P. aeruginosa induit le clivage de la VE-cadhérine, une protéine des jonctions intercellulaires, par l'action de la protéase LasB sécrétée par les bactéries. Le clivage de la VE-cadhérine entraîne une perte d'intégrité de l'endothélium, permettant aux bactéries d'accéder au domaine basolatéral des cellules. Les toxines du Système de Sécrétion de Type 3 peuvent être alors injectées dans la cellule, provoquant une intoxication cellulaire majeure. Le franchissement de la barrière épithéliale s'opère par un mécanisme très différent. Par microscopie confocale en temps réel, nous montrons que P. aeruginosa transmigre par une voie paracellulaire, en exploitant des faiblesses jonctionnelles aux sites de divisions et de morts cellulaires. Ce processus de transmigration requiert l'action coordonnée des pili de Type IV, du flagelle et de toxines du Système de Sécrétion de Type 3. / P. aeruginosa is one of the main pathogens responsible for nosocomial infections. Acute infections by this bacterium are associated with high rates of morbidity and mortality, especially when bacteria disseminate in the bloodstream. In most situations, blood infection is the consequence of the crossing of two essential tissue barriers by P. aeruginosa: the epithelium for the mucosa and the endothelium for the blood vessel. Although these events are critical steps for systemic spread of bacteria, the mechanisms involved in the penetration of the pathogen in the organism are poorly understood. For the endothelium, we demonstrate that P. aeruginosa induces the cleavage of VE-cadherin, a protein of endothelial junctions, by the action of LasB, a protease secreted by the bacteria. VE-cadherin cleavage induces a loss of integrity of the endothelium, allowing bacterial access to the cellular basolateral domain. Once in this location, the Type 3 secretion system may inject toxins into the cell, triggering a major intoxication process. Crossing of the epithelial barrier involves a very different mechanism. Using real-time confocal microscopy, we show that P. aeruginosa uses a paracellular route to transmigrate, exploiting junctional weaknesses at sites of cell division and cell death. This transmigration process requires the coordinate actions of Type IV pili, the flagellum and toxins of the Type 3 secretion system.

Thesis deals with ?the issue of awareness of nosocomial infections from undergraduate students of Bachelor and Master degree from Health education field at the University of South Bohemia in the Czech Budejovice.? This is very timely topic as nosocomial infections are a global economic and clinical problem not only for the present time but also for the future. Thesis is divided into two parts. Details of nosocomial infections, epidemic processes, agents of these infections, hand hygiene, prevention, health education, healthy lifestyle, immunity and support options for immune system are described in the theoretical part. The practical part describes the research problem, formulates hypothesis and shows statistical methods for research. The aim of this thesis was to find out the awareness of nosocomial infections from students of Bachelor and Master degree of VKZ at JU in the Czech Budejovice. Further I tried to compare this knowledge with respect to the age, education and field in which they act. I am trying to find out the possible way of prevention, personal protection against nosocomial infections moreover subjective perception of information related to this problem from respondents. I used the basic way of collecting data for achievement the given aim such as questionnaire in the aim group. There were used basic statistical methods suitable for analysis of categorical data. These results are illustrated in pie chart and bar chart for better interpretation. Test of the main hypothesis and working hypotheses are statistically made by 2 ? test. There was used Fisher factorial test in case there would be break prerequisite for correct usage of the previous test. The results of these tests are interpreted on the base of , with 95 % of reliability. I set this hypothesis in my thesis: ? Better knowledge will have students whose high school education was connected with the problems of health care. ? The result shows better knowledge for these students than for students from other high school however this difference was not statistically important. From all tests was found out that all students know the right definition of nosocomial infection however they have significantly less information related to the prevention against nosocomial infection. This thesis should give us food for thought about this problem and should change the attention to the health and the health of others and the possibility of further education.

The Diploma thesis provides basic information about the incidence of nosocomial infections, especially about the process of spreading infections, their subdivision according various aspects, major means of nosocomial infections, and about methods of surveillance. Investigative part of the thesis is aimed to describe the incidence of nosocomial infection, which can be used as quality indicator of hospital care, including the spectrum of the most frequent etiological microbial agents and their resistance against antibiotic treatment. There were used mixed research methods to process the investigative part of the thesis because the methods were quantitative and qualitative. The analysis of the data represents main part of the thesis. The research was carried out in the district hospital, namely in The Hospital Strakonice, a.s.. There were monitored infections at operation sites, between Jan 1, 2011 and Dec 31, 2011 at the surgical and gynaecology units. There were also monitored infections of the blood stream between Jan 1, 2009 and Dec 31, 2011 at all departments. The research group was formed by inpatients staying in The Hospital Strakonice, a.s., who were after surgical procedure or those, who were catheterized central blood stream in defined time period.

The present thesis focuses on nosocomial infections and their causes. The theoretical part summarizes information on especially the sources of these infections, the way of their transfer and the most frequent infection agents. Clostridium difficile is studied in more detail. The illness caused by this pathogen leads to the complications especially with in-patients with a previous antibiotic therapy and immuno-compromised individuals. And this is the problem the present thesis is also concerned with. The thesis also divides nosocomial infections by their clinical manifestations and contains basic anti-epidemic measures and surveillance methods. Its empirical part focuses on the description of an occurrence of select nosocomial infections in Strakonice Hospital, a.s., especially an occurrence of the Clostridium difficile pathogen and methicillin-resistant Staphylococcus aureus (MRSA).

Made available in DSpace on 2016-12-23T13:55:57Z (GMT). No. of bitstreams: 1 Descricao dos episodios de candidemia de origem nosocomial.pdf: 1812015 bytes, checksum: 9c5089ff58847dbbef9c102928ca12c2 (MD5) Previous issue date: 2006-09-04 / Este trabalho foi um estudo descritivo, que descreveu os episódios de candidemia nosocomial ocorridos no Hospital Universitário Cassiano Antônio de Moraes (HUCAM), entre 1.º de março de 2003 e 28 de fevereiro de 2006. Seu objetivo foi definir as taxas de prevalência e mortalidade desses espisódios, identificar as espécies envolvidas e relacionar a freqüência dos fatores de risco entre adultos e recém-nascidos (RNs), bem como entre os episódios de candidemia por Candida albicans (CA) e por Candida não-albicans (CNA). A metodologia Incluiu os casos de forma consecutiva, à medida que foi detectada hemocultura positiva para esses fungos. A coleta de dados dos pacientes foi realizada com base no prontuário médico, por meio de formulário padronizado e analisados utilizando o programa Social Package Statistical Science e englobando 45 casos de candidemia, sendo dezenove casos (42%) em neonatos. Foi observado que a incidência de candidemia nosocomial no HUCAM foi de 2,0/10.000 pacientes-dia, 1,9/1.000 altas e 16/10.000 admissões, sendo maior nos pacientes internados em unidades de terapia intensiva. As espécies não-albicans predominaram e Candida parapsilosis foi mais incidente entre os RNs; os grupos de pacientes susceptíveis mais envolvidos foram aqueles com internação em torno de três semanas, com síndrome séptica aguda e em uso de antibióticos; a freqüência dos fatores de risco foi similar entre os adultos e os RNs, assim como entre os episódios devidos a CA e os devidos a CNA; maior utilização de nutrição parenteral total foi encontrada entre os RNs e de diálise, entre os adultos (p < 0,05); a taxa de mortalidade global foi de 44% entre os adultos e de 58% entre os RNs; e a taxa de mortalidade atribuída foi de 16% entre os adultos e 26% entre os RNs. Foi concluído que a incidência de candidemia no HUCAM foi alta e associada com substancial mortalidade. / This work was a descriptive study, which described the episodes of nosocomial candidemias occurring at Hospital Universitário Cassiano Antônio de Moraes (HUCAM), between March 1st, 2003 and February 28th, 2006. Its aim was to define the rates of prevalence and mortality of these epidsodes, to identify the species involved and to relate the frequency of the risk factors among adults and newborn (NBs), as well as the epidsodes among candidemias caused by Candida albicans (CA) and Candida non-albicans (CNA). The methodology included the cases in a consecutive way, as positive hemoculture was detected for these fungi. The date collection of patients was based on the medical records, through a standard form and it was analyzed using the Social Package Statistical Science program, including 45 cases of candidemias, being nineteen cases (42%) in NBs. It was observed that the incidence of nosocomial candidemia at HUCAM was 2.0/10.000 patient-day, 1.9/1.000 discharges and 16/10.000 admissions, being greater in patients interned in intensive therapy unity. the CNA predominated and C. parapsilosis was more incidente among the NBs; the group of susceptible more involved were those interned for 3 weeks with acute septical syndrome and in use of antibiotics; the frequency of risk factor was similar among the episodes due to CA and the ones due to CAN; greater utilization of total parenteral nutrition was found in the NBs and the dialysis, among the adults (p< 0,005); the total mortality rate was 44% among adults and 58% among the NBs. And the attributed mortality rate was 16 in adults and 26% in NBs. It was concluded that incidence of candidemias at HUCAM was high and associated with substantial mortality.