Early Goal Directed Therapy (EGDT) has been thoroughly researched and clinically supported to be effective at lowering morbidity and mortality associated with severe sepsis and septic shock. Due to the strengths of its efficacy, it has been integrated as an essential component of the Surviving Sepsis Campaign. However, very few studies have explored the barriers that affect compliance of the protocol in actual practice. The purpose of this study was to synthesize current research findings regarding nursing barriers associated with EGDT. This research was limited to studies performed in the United States between 2003-2012, with patients at least 18 years old, and with data obtained from studies conducted within emergency departments (EDs) only. These findings may serve to help increase the compliance rate with the protocol among nurses in the ED. Findings indicated that compliance rates were mostly affected by two major barriers: 1) Lack of knowledge regarding the presentation and management of sepsis and septic shock, and 2)Lack of resources in the ED to perform the protocol to its full potential. Limitations of the review noted were that most research studies used were in major academic hospitals which limited the generalizability of the findings to other hospital settings. Nursing education should emphasize early recognition and aggressive treatment of sepsis. Future research should focus on addressing the most efficient ways to educate nurses on sepsis presentation and management and the ways these can be implemented in practice.

The presence of nitrates and phosphorus in ground water is a worldwide problem. A septic tank with drainfield that is conventionally designed does not typically remove nitrogen in the form of nitrates. The main risks are in "Blue baby" syndrome and suspected carcinogenic effect of nitrates on humans and the nutrient enrichment of receiving waters. In some areas nitrate and phosphorus removal are essentially required. Thus the information in this report concentrates on using media in the drainfield for the removal of nitrogen and phosphorus. Extensive work has been conducted in the past few decades in order to find suitable media for denitrification with high selectivity towards nitrogen. Column experiments were conducted at the University of Central Florida to simulate the actual septic tank drainfield using mixes of fine sand. In one of the columns Sawdust and Tire Crumb were added to the Sand (STS) and in the other column Paper and Tire Crumb were added to the Sand (STP). Tire crumb was added as a carbon source required for better denitrification and for sorption. The columns were dosed daily using regular septic tank effluent and it was a continuous batch system. Samples were taken after a hydraulic retention time (HRT) of 24 hours and comparisons were made of the effluent with the influent to show percentage removal of nitrogen (nitrates, ammonia and total nitrogen), phosphorus (ortho-phosphorus and total phosphorus) and BOD. STS and STP columns showed more than 90% removal for all parameters (nitrates, ammonia, total nitrogen, ortho-phosphorus, total phosphorus, BOD). The results indicate that the investigated media blend (Black and GoldTM Nugget Mix) has the potential for successful application in full scale operations. It is recommended that Black and GoldTM Nugget Mix be used to achieve the required removal of the nutrients.

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Septic tanks are utilized by many households across North America for wastewater treatment. Despite the economic and environmental importance of septic tanks, there has been limited innovation in septic tank design and research on the microbial communities responsible for wastewater treatment within these systems. InnerTube systems are septic tanks that employ a novel design to reduce solid accumulation in comparison to conventional septic tanks. For this project, 16S metabarcoding was employed to characterize conventional and InnerTube septic tank microbial communities and evaluate relationships between community composition, system design, and treatment efficacy. Wastewater was sampled along the length of InnerTubes to determine patterns of microbial succession and how they may impact InnerTube function. Wastewater was separated into liquid and solid fractions to identify differentially abundant taxa in each fraction. Populations of methylotrophic methanogens increased with distance from the InnerTube inlet. Solid communities were differentially more abundant in methanogens than liquid communities. Higher rates of solid degradation in InnerTubes may be due to longitudinal stratification of substrates and functionally distinct communities and the activity of methanogenic biomass. Septic tanks throughout Ontario were also surveyed to evaluate the effect of system design (conventional vs. InnerTube) and operational flow (single-pass vs. recirculation) on microbial community composition and to identify taxa correlated with chemical oxygen demand (COD) reduction. Single-pass InnerTube communities were more abundant in Pseudomonas which was attributed increased availability of long-chain fatty acid substrates. Recirculating conventional communities were more abundant in Arcobacter and Desulfomicrobium which was attributed to greater resistance to oxidative stress. Desulfovibrio and Brevundimonas were positively correlated with COD reduction. These putative hydrogen producers may facilitate greater COD reduction by forming syntrophic relationships with hydrogenotrophic methanogens. The findings of this project may be used to develop bioaugmentation inoculum, system designs, or operational strategies to optimize septic tank performance. / Thesis / Master of Science (MSc) / Septic systems (anaerobic digesters) are extensively used for on-site wastewater treatment. We evaluated the use of next-generation DNA sequencing to (1) assess the variability of septic system microbial communities and (2) to investigate relationships between communities and septic system type/performance. Microbial communities within septic systems were determined to be heterogeneous. Analyses also indicated that communities were highly variable between septic systems. Despite this variability, specific system types exhibited distinct microbial profiles. System performance was positively correlated with the abundance of hydrogen-producing bacteria. These results demonstrate the potential of next-generation DNA sequencing as a new tool to augment traditional wastewater analyses.

Between 1970 and 2010 almost one-third of drinking water related waterborne disease outbreaks reported to the US Centers for Disease Control and Prevention were associated with systems dependent on untreated groundwater (i.e., most commonly, household wells). This is unsurprising, given that numerous past efforts to monitor household well water quality have indicated a high prevalence of fecal coliforms and/or E. coli at the point of use. Non-point sources of pollution, including septic tank leakages and poorly constructed drain fields, have been identified as the leading risk factors associated with outbreaks in households dependent on groundwater. Ideally, the integration of emerging source tracking (ST) analyses in well monitoring programs could be used to identify whether the presence of fecal indicator bacteria (FIB) is associated with human or non-human sources in order to inform remediation strategies. However, the application of ST to groundwater has been limited, and the interpretation of data is consequently difficult. This research compares the fate and transport of FIB (E. coli and enterococci) with a chemical (optical brighteners, OB) and a molecular (Bacteroides HF183) ST target in order to evaluate their potential use as indicators of water quality issues in private drinking water systems. Eighteen PVC soil columns were constructed in an outdoor soil column facility to represent small-scale septic drainfield models; they received synchronized doses of primary-treated wastewater twice daily and were monitored bi-weekly over a 7-month period. Columns were subject to variable influent loading rates of wastewater effluent, and differing degrees of soil compromisation (i.e. synthetic solution channels). Results show that while column effluent volume and constituent levels were related to dosage, they were not always related to soil compromisation (ANOVA, p < 0.05). E. coli and enterococci concentrations were associated with effluent volume and OB levels (Spearman's rank, p < 0.05). The presence of Bacteroides HF183 was not strongly associated with the other measured ST target levels (Point-biserial correlation, p < 0.05). Findings from this study suggest surface water ST methodologies may have a role in groundwater quality monitoring efforts. Quantifying the relative recovery of ST targets and FIB from controlled groundwater simulations will assist in the development of strategies to identify non-point sources of human wastewater pollution efficiently and effectively to inform remediation. / Master of Science

This diploma thesis consists of two parts, part research and part attachments. The first section describes the literary problems of today's way of cleaning wastewater from small producers and characteristics of wastewater. The work is focused on the aspect of nature and all of these methods are directed towards this direction. The literary section is devoted to anaerobic environment, which is just one of the natural ways of treatment of waste water, in our case in a septic tank. The second part of the thesis deals with modeling of flow and behavior of sludge and water mixture in the cesspit septic tank sludge with variable densities and flow speeds. Modeling and calculations are made using COMSOL Multhiphysics. The conclusion is then summarized findings from the flow cesspit septic tank with the results and the assessment of whether a septic tank still has its place among the modern methods of wastewater treatment.

Die Sepsis ist ein gefürchtetes Krankheitsbild, das in hochentwickelten Industrienationen mit einer hohen Mortalität verknüpft ist und damit zu den häufigsten Todesursachen gehört. Die Pathomechanismen dieses komplexen und heterogenen Krankheitsbildes zu entdecken, gehört momentan zu den Hauptinteressengebieten der Sepsisforschung. Da die Interpretation klinischer Studien aufgrund der Heterogenität des Patientenguts schwierig ist, kommt der Entwicklung adäquater Tiermodelle eine entscheidende Bedeutung zu. Die hierbei gängigen Tiermodelle in Mäusen weisen jedoch Unzulänglichkeiten auf, die die Übertragung der in Tierexperimenten gewonnen Daten auf den klinischen Kontext nur teilweise ermöglichen. Eine Brücke kann hierbei das Tiermodell der humanisierten Maus schlagen, in der, durch Transplantation mit humanen hämatopoetischen Stammzellen, ein humanes Immunsystem reift. Die vorliegende Arbeit beschäftigt sich mit der Fragestellung, inwieweit die humanen Immunzellen in der humanisierten Maus in der Lage sind, auf LPS als Stimmulus zu reagieren. Darüberhinaus wird die Nutzung der Endotoxämie in der humanisierten Maus als alternatives Sepsismodell im Bezug zum klinischen Kontext untersucht. Hierbei ergab sich eine mögliche Nutzung des Endotoxämiemodells in der humanisierten Maus zur genaueren Erforschung des Zytokinmilieus, sowie neuer Surrogatmarker wie Pentraxin 3. Bezüglich der Reaktion einzelner immunologischer Subpopulationen und deren Bedeutung für die Klinik scheint eine Untersuchung an Modellen, die eine B- und T-Zell-Reifung nachvollziehen können und in der murine Residualzellen möglichst gering vorhanden sind, als sinnvoll.

O meropenem é um carbapenêmico de amplo espectro e alta potência, largamente prescrito para tratamento de infecções graves causadas por bactérias sensíveis gram-negativas em pacientes críticos internados em Unidades de Terapia Intensiva. O objetivo do presente estudo foi avaliar a efetividade do antimicrobiano em pacientes grandes queimados, recebendo a dose recomendada 1 g q8h através da infusão intermitente de 0,5 hora que ocorreu até 2014 (grupo 1) comparada a infusão estendida de 3 horas que ocorreu após esse período (grupo 2). Investigaram-se 25 pacientes sépticos de ambos os sexos (6F/19M), 26 (21-34) anos, medianas (interquartil), 70 (60-75) kg, superfície corporal total queimada (SCTQ) 35 (16-42)%, SAPS 3: 55 (45-59) e Clcr 129 (95-152) ml/min que foram distribuídos em dois grupos. Registrou-se trauma térmico pelo fogo em 19/25 e trauma elétrico no restante dos pacientes (6/25), lesão inalatória (17/25), intubação orotraqueal e a necessidade de vasopressores em 18/25 pacientes. Duas amostras de sangue foram coletadas (3ª e 5ª horas) para dosagem sérica do meropenem por cromatografia líquida no período precoce do choque séptico. A farmacocinética foi investigada pela aplicação do modelo aberto de um compartimento e a abordagem PK/PD foi realizada com base no novo índice recomendado 100%f&#916;T>CIM. Evidenciou-se aumento do PCR 224 (179-286) versus 300 (264-339) mg/L, p=0,0411 e neutrofilia: 12 (8-17) versus 8 (2-15) células/mm3, p=0,1404, respectivamente nos grupos de infusão estendida versus infusão intermitente. Os níveis séricos obtidos mostraram diferença significativa entre grupos (p<0,0001) tanto para o pico 21 (21-22) mg/L versus 44 (42-45) mg/L, como para o vale 7,8 (7,3-9,5) mg/L versus 3,0 (2,6-3,7) mg/L. A farmacocinética mostrou-se alterada nos dois grupos frente aos dados de referência reportados em voluntários sadios. Significativa alteração ocorreu em diferentes proporções pela comparação entre os grupos relativamente à constante de eliminação 0,190 (0,157-0,211) versus 0,349 (0,334-0,382) h-1; meia-vida biológica 3,6 (3,3-4,4) versus 2,0 (1,8-2,1) h; depuração total corporal 8,6 (8,2-8,9) versus 5,3 (5,2-5,4) L/h; volume de distribuição 41,8 (39,9-44,5) versus 15,4 (14,1-16,2) L (p<0,0001). A infecção de ferida foi a mais prevalente nos dois grupos com 47% versus 38% dos isolados, sendo a Klebsiella pneumoniae, a principal enterobactéria. A abordagem PK/PD para patógenos CIM 1 a 4 mg/L mostrou cobertura até CIM 4 mg/L para a infusão estendida e até CIM 2 mg/L para infusão intermitente. Em conclusão, demonstrou-se a superioridade da infusão estendida decorrente de alterações na farmacocinética do meropenem em pacientes grandes queimados. O aumento do volume de distribuição contribuiu para o prolongamento da meia-vida e dos altos níveis de vale registrados, o justifica o impacto na cobertura antimicrobiana após infusão estendida e controle das infecções com cura desses pacientes. / Meropenem is a broad-spectrum agent widely prescribed for the treatment of septic shock caused by gram-negative susceptible strains in critically ill patients from the Intensive Care Units. Subject of the present study was to evaluate the drug effectiveness in critically ill septic burn patients in SIRS at the early period of septic shock receiving the recommended dose of Meropenem 1 g q8h by intermittent 0.5 hour infusion or the extended 3 hour infusion. Twenty-five septic patients were: (6F/19M), 26 (21-34) years, medians (quartiles), 70 (60-75) kg, total burn body surface (SCTQ) 35 (16-42) %, SAPS 3: 55 (45-59) and Clcr 129 (95-152) ml/min. Thermal trauma was registered in 19/25 and electrical trauma in the remaining patients (6/25), inhalation injury (17/25), orotracheal intubation and vasopressor requirement in 18/25 patients. Patients were distributed in two groups on the basis of the duration of drug infusion that occurred for the patients of group 1 (1g q8h 0.5 hr) until 2014, December in the hospital. In addition, the extended 3 hours infusion occurred after that period for patients enrolled afterwards (group 2). Pharmacokinetics was investigated after blood sampling at the third (3rd) hour and the fifth (5th) hour of starting the meropenem infusion. Serum drug measurement was done by liquid chromatography. A one compartment open model was applied and kinetic parameters were estimated. PK/PD approach based on the new recommended index of drug effectiveness 100% f&#916;T>MIC was performed, on the basis on PK parameters and the minimum inhibitory concentration, PD parameter. It was demonstrated a significant difference between groups (p <0.0001) related to the trough levels 7.8 (7.3-9.5) mg/L versus 3.0 (2.6-3.7) mg/L, respectively after extended infusion or intermittent infusion. Concerning the pharmacokinetics, it was shown profound changes on meropenem kinetic parameters in both groups of burn patients by comparison with the reference data reported in healthy volunteers. In addition, it is important to highlight that significant changes occurred also by comparison of PK data between groups of patients related to the parameters: elimination constant 0.190 (0.157-0.211) versus 0.349 (0.334-0.382) h-1; biological half-life 3.6 (3.3-4.4) versus 2.0 (1.8-2.1) hr; total body clearance 8.6 (8.2-8.9) versus 5.3 (5.2-5.4) L/hr; volume of distribution 41.8 (39.9-44.5) versus 15.4 (14.1-16.2) L. Concerning the inflammatory biomarker an increase of C-reactive protein was registered in both groups of septic patients in SIRS: 224 versus 300 mg/L, p = 0.0411, after the extended infusion versus intermittent infusion, respectively. Wound and bone were the most prevalent sites of infection in those patients of both groups. It was shown in the isolates the prevalence of Gram-negative strains 54/83 (65%) that were distributed in Enterobacteriaceae, K. pneumoniae 7/30 (23%), and Non-Enterobacteriaceae, P. aeruginosa 13/54 (24%) followed by Acinetobacter baumannii 11/54 (20%). Drug effectiveness against susceptible strains was demonstrated by PK/PD approach up to 4 mg/L over 2 mg/L, after the extended infusion or after intermittent infusion, respectively. In conclusion, the superiority of the extended infusion in septic burn patients at the earlier period of septic shock was demonstrated, once considerable increases on volume of distribution impacted the drug effectiveness of these patients. Cure was obtained by meropenem monotherapy in 22/25 patients; only three patients (3/25) received meropenem - colistine combined therapy due to Acinetobacter baumannii isolated.