Bacterial Infections and Mycoses Commons^™

The Impact Of Social Determinants Of Health On Adherence To Urinary Tract Infection Treatment: A Scoping Review, Barrett S. Patel, Ms, Bsn, Rn, Emily A. Gentry, Bsn, Rn, Sally Humphrey Dnp, Aprn, Cpnp-Pc, Bobby Bellflower Dnsc, Nnp-Bc, Faanp, Fnap

Doctor of Nursing Practice Projects

Purpose/Background

Urinary tract infections (UTIs) are a common diagnosis among children. Patients must fully comply with treatment regimens to reduce the risk of recurring UTIs and prevent long-term complications. This scoping review aims to evaluate the literature and examine the association between screening for social determinants of health (SDH) and adherence to UTI treatment.

Methods

A thorough literature search via PubMed, Cochrane Library, Elsevier Clinical Key, CINAHL, and JAMA was conducted with the following keywords: Pediatric UTI, Adherence to Treatment Plans, Social Determinants of Health, Social Needs Screening, and others. Ten articles were appraised for their evidence and quality. The …

Pkpd-Model Based Preclinical Characterization Of The Activity Of Spectinamide 1599 Against Mycobacterial Subpopulations. And The Identification Of Potential Partners For Combination Therapy, Zaid Hanif Temrikar

Theses and Dissertations (ETD)

Tuberculosis is one of the top 10 causes of death worldwide and the leading cause of death from a single infectious agent prior to COVID19. Mycobacterium tuberculosis (Mtb) is the causative agent of TB. The interaction between Mtb and the immune system leads to development of diverse environmental niches and physiology within the lung of the TB patients. Mtb is thought to adapt and thrive in such an environment by transforming to different phenotypic variants. Such variants are difficult to kill and are thought to prolong TB pharmacotherapy. Spectinamide 1599 is a synthetic modification of spectinomycin that has demonstrated excellent …

The Effectiveness Of Increasing Frequency Of Central-Line Dressing Changes And Monitoring On Clabsi Rates: A Scoping Review, Jacob Schmidt, Bsn, Rn, Ccrn, Georgia Brown, Bsn, Rn, Laura Dickey, Agpcnp-C, Lauren Faulkner, Bsn, Rn, Margaret Harvey, Phd, Aprn, Acnp-Bc, Chfn

Doctor of Nursing Practice Projects

Abstract

Purpose/Background

Central lines provide many benefits to critically ill patients; however, there are additional risks with them, including central line-associated bloodstream infections (CLABSIs). CLABSIs place patients at increased risk for morbidity and mortality, longer length of stay, and higher medical costs. Studies evaluating various methods of reducing CLABSIs have been performed. This scoping review was completed to determine the effectiveness of frequent central-line dressing changes and increased monitoring on the incidence of central-line associated blood stream infections in adults with central-lines.

Methods

An extensive database search through the University of Tennessee Health Science Center (UTHSC) Online Library was performed …

Investigation Of Clinically Relevant Fluconazole Resistance Mechanisms In The Fungal Pathogen Candida Parapsilosis, Laura Anne Doorley

Theses and Dissertations (ETD)

Invasive candidiasis is a severe fungal infection associated with significant morbidity and mortality, particularly among the critically ill and immunocompromised. Candida parapsilosis is the most common non-albicans species causing invasive Candida infections in pediatric and neonatal populations worldwide and is particularly common in the countries of South America, Western Asia, Mediterranean Europe, and Southern Africa. For many of these countries, fluconazole and other triazoles are the first line antifungal agents used for effective treatment of invasive Candida infection. Until recently, rates of fluconazole resistance among C. parapsilosis isolates were relatively low, therefore the determination of clinically relevant resistance mechanisms in …

Physiologically-Based Pharmacokinetic (Pbpk) Modeling For The Preclinical Development Of Spectinamide Antibiotics, Keyur R. Parmar

Theses and Dissertations (ETD)

Despite being an ancient disease caused by Mycobacterium tuberculosis (Mtb) and after decades of research, tuberculosis (TB) still affects millions of people every year worldwide. In 2018, the World Health Organization (WHO) reported that 10 million people developed tuberculosis and 1.5 million died of the disease. With the increase in the multidrug-resistant (MDR) and extensively drug-resistant (XDR) cases, the treatment for TB with the standard first and second-line therapy is becoming increasingly difficult. Therefore, there is an urgent need to find new anti-TB drugs as combination partners of existing and experimental classes of antimicrobial agents to shorten and simplify the …

Computer-Aided Drug Discovery For Helicobacter Pylori, Nicole Ann Vita

Theses and Dissertations (ETD)

Helicobacter pylori is a high-priority drug-resistant pathogen and is currently the only bacteria considered to be a class I carcinogen and there is a critical need to identify novel chemical matter to treat H. pylori infections. Hp is responsible for greater than 60% of gastric cancer related deaths and 89% of all gastric cancer morbidities. In a previous study, our lab identified novel Hp thienopyrmidine inhibitors that target respiratory complex I, an essential enzyme in respiration. Respiratory complex I is a large asymmetric multidomain and membrane bound enzyme and due to these innate features, it is not practical for biophysical …

A Cloning-Free Recyclable System For Crispr-Cas9 Mediated Mutant And Reversion Construction In Candida Albicans Clinical Isolates, Amanda K. Vogel

Theses and Dissertations (ETD)

Candida albicans is a ubiquitous opportunistic fungal pathogen and one of the most prevalent causes of fungal diseases worldwide. The reference isolate SC5314 is one of the most widely used strains for both experimental and genetic studies, but it is becoming increasingly evident that genetic diversity in clinical isolates plays an important role in antifungal resistance, virulence, and pathogenicity. These recent discoveries highlight the need for genetic tools that are capable of investigating genes in multiple strain backgrounds. Here we build on the SAT1-flipper method and combine it with CRISPR-Cas9 technology to achieve cloning-free homozygous deletion in a single transformation …

Screening For Social Determinants Of Health To Improve Care In Pediatric Patients With Recurrent Urinary Tract Infections: A Scoping Review, Emily Gray Msn, Fnp-C, Michelle Rickard Dnp, Cpnp-Ac

Doctor of Nursing Practice Projects

Purpose: To describe what is known about how SDoH screening impacts adherence to treatment in pediatric patients with recurrent UTIs.

Nursing Perspectives And Opinions On Early Or Delayed Sepsis Treatment: A Mixed Methods Approach, Pamela L. Harris

Theses and Dissertations (ETD)

Purpose. Each year at least 1.7 million adults in America develop sepsis. Sepsis can lead to life threatening organ dysfunction, severe hypotension, and death when severe sepsis or septic shock is involved. Sepsis is responsible for 50% of acute kidney injury (AKI), which is the most common form of organ dysfunction seen in critical care. Sepsis associated AKI results in loss of, or decreased renal function, is associated with adverse long-term outcomes, and carries a higher mortality rate than non-septic AKI, sepsis without AKI, or septic shock without AKI. Surviving sepsis guidelines suggests a 1-hour window from the time of …

Sepsis: Do The Clinical Criteria Support The Medical Coding?, April M. Insco

Theses and Dissertations (ETD)

Background: Sepsis is a condition that can be very costly and very deadly. Diagnosing sepsis can be challenging as there is not one specific test that will identify whether a patient has sepsis and there are varying opinions as to the true definition of sepsis. The definition of sepsis used for this research is a combination of System Inflammatory Response Syndrome (SIRS) with an identified infection. Medical Coders must review the documentation provided in a medical record to accurately assign an ICD-10-CM code. Administrative data is then used to provide statistical information for research purposes. When coded data is not …

Updates In The Pharmacologic Prophylaxis And Treatment Of Invasive Candidiasis In The Pediatric And Neonatal Intensive Care Units, James Hunter Fly, Seerat Kapoor, Kelly Bobo, Jeremy S. Stultz

Faculty Publications

Purpose of review The goal of this review was to provide an update on the prevention and treatment options for invasive candidiasis (IC) in the neonatal intensive care unit (NICU) and pediatric intensive care unit (PICU).

Recent findings Studies have further validated the use of fluconazole for IC prophylaxis among high-risk patients in the NICU. It remains unclear if prophylaxis leads to resistance development and the ideal dosage regimen is still not clear. Recent studies have been published comparing caspofungin and micafungin to amphotericin B and illustrated similar efficacy outcomes in the NICU. Micafungin now has approval from the United …

Impact Of Social Determinants Of Health On Adherence To Urinary Tract Infection Treatment Recommendations: A Scoping Review, Charles W. Stewart Cpnp, Diana Dedmon Dnp, Aprn, Fnp-Bc

Doctor of Nursing Practice Projects

Purpose/Background: Pediatric health is significantly affected by social determinants of health. Screening for and addressing social determinants of health helps to decrease negative effect on health outcomes. The purpose of this project is to determine if there is an association between addressing or not addressing social determinants of health by the healthcare provider and parents’ adherence to treatment recommendations in children with urinary tract infections.

Methods: Between October 2020 and November 2021, a literature review was performed to obtain data from studies regarding urinary tract infections, social determinants of health and adherence to treatment recommendations. The University of Tennessee Health …

Central Line Associated Blood Stream Infection Prevention With Use Of Disinfection Caps: A Scoping Review, Marianne E. Person, Jessica Biggs, Elizabeth Ross, Margaret Harvey Phd, Aprn, Acnp-Bc, Chfn

Doctor of Nursing Practice Projects

Purpose/Background Central lines provide lifesaving uses, but they also place the patient at risk for central line associated blood stream infections (CLABSI). Catheter location, length of stay, handwashing, dressing changes, and disinfection of ports before use are all factors to prevent CLABSIs, yet sometimes these measures are not enough. Disinfecting caps are another way to decrease central line infection, however not all hospitals use this method. This scoping review aims to compare CLABSI rates with and without the use of disinfecting caps for the duration of central line use in intensive care patients.

Methods From August 2019 to September 2021, …

Cellular Dynamics And Disease Outcome Of Type 3 Streptococcus Pneumoniae Clinical Isolates Differ Between Strains, Taylor Rae Plunkett White

Theses and Dissertations (ETD)

Streptococcus pneumoniae is a bacterial pathogen that continues to be a major cause of disease around the world. It is not only the number one cause of bacterial pneumonia but also the cause of about 15% of the deaths of children under 5 around the world. There is a lot of research done on this organism, but with around 100 known serotypes and each one producing a unique capsule, there is still much more to be studied. The Etiology of Pneumonia in the Community (EPIC) study conducted by the CDC observed the burden of hospitalizations caused by pneumonia while determining …

Impact Of Central Line Bundle Care On Reduction Of Central Line Associated-Infections: A Scoping Review, Alisha James-Scott Msn, Fnp-C, Rachel Savoy Msn, Fnp-Bc, Donna Lynch-Smith Dnp, Acnp-Bc, Apn, Ne-Bc, Cnl, Tracy Mcclinton Dnp, Ag-Acnp-Bc, Apn

Doctor of Nursing Practice Projects

Purpose/Background Central venous catheters (CVC) are typical for critically ill patients in the intensive care unit (ICU). Due to the invasiveness of this procedure, there is a high risk for central line-associated bloodstream infection (CLABSI). These infections have been known to increase mortality and morbidity, medical costs, and reduce hospital reimbursements. Evidenced-based interventions were grouped to assemble a central line bundle to decrease the number of CLABSIs and improve patient outcomes. This scoping review will evaluate the literature and examine the association between reduced CLABSI rates and central line bundle care implementation or current use.

Methods A literature review was …

Antibiotic Tolerance And Heteroresistance: Associated Fitness Costs And Potential In Evading Antibiotic Killing, Tina H. Dao

Theses and Dissertations (ETD)

Streptococcus pneumoniae is a prominent human pathogen that causes both invasive and non-invasive diseases, such as otitis media, pneumonia, meningitis, and bacteremia. Although it is frequently an asymptomatic colonizer of the human nasopharynx, S. pneumoniae is a major cause of morbidity and mortality in the immune compromised population, young children, and the elderly. Up until the 1970s, S. pneumoniae was susceptible to almost all antibiotics. Since then, this pathogen has gained resistance to a variety of antibiotic treatments, including beta-lactams, macrolides, and fluoroquinolones.

In the first chapter, we focused on fluoroquinolone resistance in S. pneumoniae. Fluoroquinolones are one of the …

Identification Of Effectors Of Synergistic Lethality In Candida Albicans-Staphylococcus Aureus Polymicrobial Intra-Abdominal Infection, Olivia Adele Todd

Theses and Dissertations (ETD)

Candida albicans, an opportunistic fungal pathogen, and Staphylococcus aureus, a ubiquitous pathogenic bacterium, are among the most prevalent causes of nosocomial infections and cause severe morbidity and mortality. Moreover, they are frequently coisolated from central venous catheters and deep-seated infections, including intra-abdominal sepsis. Relatively little is known about the complex interactions and signaling events that occur between microbes and even less so how microbial “cross-talk” shapes human health and disease.

Using a murine model of polymicrobial intra-abdominal infection (IAI), we have previously shown that coinfection with C. albicans and S. aureus leads to synergistic lethality whereas monomicrobial infection is nonlethal. …

Delineating The Upc2a Regulon In Candida Glabrata, Yu Li

Theses and Dissertations (ETD)

Candida glabrata is the second most common cause of invasive candidiasis. Intrinsic resistance has greatly limited the utility of the triazole antifungal, fluconazole, in the treatment of invasive fungal infection. The transcription factor Upc2 regulates the expression of sterol biosynthesis genes in yeast. Disrupting UPC2A in C. glabrata greatly increases its susceptibility to fluconazole (FLU) in both FLU-susceptible and -resistant clinical isolates. Therefore, the Upc2A and its target genes represent a potential pathway for overcoming FLU resistance in C. glabrata. We aimed to delineate the Upc2A regulon to determine its target genes involved in FLU resistance. Transcriptome sequencing (RNA-seq) analysis …

Model-Based Dose-Exposure-Response Assessment For Lead And Backup Spectinamide In A Mouse Model Of Tuberculosis, Santosh Janardan Wagh

Theses and Dissertations (ETD)

Despite decades of research, tuberculosis remains the oldest pathogen-based disease that is the leading cause of death from a single infectious agent. Among many anti-tubercular therapies under investigation, the semisynthetic compounds spectinamides are a promising novel class of anti-tuberculosis agents. One such lead candidate, spectinamide 1810, and backup spectinamide 1599 have demonstrated excellent efficacy, safety, and drug-like properties in various in vitro and in vivo assessments. The dose-ranging and dose fractionation studies were designed to characterize the dose-exposure-response relationship for lead and backup spectinamide in a mouse model of Mycobacterium tuberculosis infection. In this current study, we used 26 and …

Role Of Cerebral Vasculature And Effect Of Circulating Exosomes In Propagation Of Systemic Inflammatory Responses Into The Central Nervous System, Mahesh Chandra Kodali

Theses and Dissertations (ETD)

Sepsis-associated encephalopathy (SAE) is an acutely progressing brain dysfunction induced by systemic inflammation. The mechanism of initiation of neuroinflammation during SAE, which ultimately leads to delirium and cognitive dysfunction, remains elusive. The goal of this project was to study the molecular events of SAE to capture its onset and progression into the central nervous system (CNS), and further identify the cellular players involved in mediating acute inflammatory signaling. Gene expression profiling on the cerebral vessels isolated from the brains of the mice treated with peripheral lipopolysaccharide (LPS) revealed that the cerebral vasculature responds within minutes to acute systemic inflammation by …

Validation And Application Of A Novel Target-Based Whole-Cell Screen To Identify Antifungal Compounds, Christian Alexander Dejarnette

Theses and Dissertations (ETD)

Traditional approaches to drug discovery are inefficient and have several key limitations that constrain our capacity to rapidly identify and develop novel experimental therapeutics. To address this, we have devised a second-generation target-based whole-cell screening assay based on the principles of competitive fitness, which can rapidly identify target-specific and physiologically-active compounds. Briefly, strains expressing high, intermediate, and low levels of a preselected target protein were constructed, tagged with spectrally distinct fluorescent proteins (FPs), and mixed together. The pooled strains were then grown in the presence of various small molecules, and the relative growth of each strain within the mixed culture …

Novel Determinants That Influence Azole Susceptibility In Candida Glabrata And Candida Albicans, Sarah Garland Whaley

Theses and Dissertations (ETD)

Despite the scientific and medical communities’ best efforts, the incidence of fungal infections in susceptible populations continues to rise. The most common cause of these opportunistic fungal infections is Candida. In fact, Candida is the fourth most common pathogen associated with nosocomial blood stream infections. Reported mortality rates for patients with candidemia vary, but have not decreased in the past fifteen years and are reported to be as high as 50%. Candida glabrata, second only to Candida albicans among Candida infections, expresses high rates of resistance to treatment with arguably the best class of currently available antifungals - …

Development Of Oral Vaccines Against Lyme Disease, Rita Raquel Dos Anjos De Carvalho E Melo

Theses and Dissertations (ETD)

Lyme Disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States and Europe. If left untreated, it can lead to permanent damage to the nervous and musculoskeletal systems. In some cases, patients that receive the recommended antibiotic therapy develop a debilitating health condition associated with substantial health care costs. Despite current preventive measures, the incidence and the geographic distribution of Lyme Disease continues to increase. Recent estimates from CDC suggest that the true number of cases of Lyme Disease in the US is approximately 300,000 per year. Yet, there is currently no vaccine …

Genetic Control Of Survival And Weight Loss During Pneumonic Burkholderia Pseudomallei (Bp) Infection, Felicia D. Emery

Theses and Dissertations (ETD)

Burkholderia pseudomallei (Bp) is a saprophytic, gram-negative aerobe and the causative agent of the disease melioidosis. Melioidosis is an infectious disease that occurs in humans and animals and is prevalent in Southeast Asia, northern Australia and other tropical areas. Transmission occurs through direct contact with the organism via ingestion, inhalation, or through open wounds and skin abrasions. Clinical presentation is extremely variable and can range from acute septicemia with bacterial dissemination to distant sites, to an isolated pulmonary infection. Treatment of melioidosis can be problematic because it is often difficult to diagnose and Bp is resistant to a diverse group …

Development And Evaluation Of Amphotericin B Loaded Iron Oxide Nanoparticles For Targeted Drug Delivery To Systemic Fungal Infections, Pavan Balabathula

Theses and Dissertations (ETD)

A targeted nanotheronostic drug delivery system to diagnose and treat life threatening invasive fungal infections (IFIs) such as cryptococcal meningitis was designed, developed, characterized, and evaluated. To address the development processes, first, iron oxide nanoparticles (IONP) (34-40 nm) coated with bovine serum albumin (BSA), loaded and targeted with amphotericin B (AMB) (AMB-IONP) was formulated by applying a layer by layer approach. Several designs (A, B, C, D, & E) of AMB-IONP were developed and their physicochemical properties such as drug loading with HPLC method, particle size, poly dispersity index (PDI), and ζ-potential using dynamic light scattering (DLS) technique, morphology with …

A Novel Mechanism Of Enhanced Susceptibility To Bacterial Pneumonia In Influenza-Infected Hosts, Hazem Elsayed Ghoneim

Theses and Dissertations (ETD)

Viruses such as influenza suppress host immune function by a variety of methods. This may result in a significant morbidity through several pathways, including facilitation of secondary bacterial pneumonia from pathogens such as Streptococcus pneumoniae. Lungresident alveolar macrophages (AMs) act as the first line of innate cellular immunity against respiratory bacterial pathogens, including pneumococcus. Therefore, they represent an attractive target for study Before investigating the impact of influenza infection on resident AMs, we first characterized different subsets of lung-resident macrophages in naïve mice using a novel in vivo labeling approach in conjunction with multicolor flow cytometric analysis and confocal microscopic …

Erg11-Mediated Azole Resistance In Candida Albicans, Stephanie Ann Flowers

Theses and Dissertations (ETD)

Although many medically important Candida species are commensal to the gut or colonizers of the skin, these organisms have the propensity to cause disease in the event of a waning immune system. Clinical manifestations of infections with Candida species can range from superficial mucosal infections to deep organ involvement usually resulting from haematogenous spread of infection. Despite significant progress made in the management of patients with fungal infections, the emergence of antifungal resistant clinical isolates creates significant problem in regards to antifungal prophylaxis and empirical treatment strategies. Antifungal resistance is associated with high mortality rates and hefty medical costs. The …

Signal Transduction And Transcriptional Regulation Pathways Essential For Azole Resistance In Candida Albicans, Erin M. Vasicek

Theses and Dissertations (ETD)

Candida albicans is the most prevalent human fungal pathogen, found as a commensal organism in the mucosa, gastrointestinal, and urogenital tracts of humans. This pathogenic fungus causes a wide spectrum of diseases, including the mucosal infection oropharyngeal candidiasis (OPC) which frequently effects patients with human immunodeficiency virus (HIV). The azole antifungals (such as fluconazole) are the most widely used and important ergosterol biosynthesis inhibitors (EBIs) for the treatment of Candida infections, including OPC. However, the azoles are fungistatic against C. albicans and therefore have limited efficacy against this organism, especially for immunocompromised patients. In C. albicans, the transcription factor Upc2 …

Toll-Like Receptors 2 And 9 Are Important For Innate Immune Cell Activation And Recruitment In Hypersensitivity Pneumonitis, Kelly J. Andrews

Theses and Dissertations (ETD)

Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by repeated inhalation of environmental antigens. The disease is characterized by alveolitis and granuloma formation; however, some patients develop chronic HP (CHP), a restrictive lung disease characterized by fibrosis. Previous studies revealed that neutrophils are recruited into the lung via a MyD88- dependent pathway and regulate disease severity through cytokine production. Toll-like receptors (TLRs) 2 and 9 recognize conserved molecular patterns present in bacteria, and signal through the adaptor molecule MyD88. The goal of my project is to investigate the role of TLRs 2 and 9 in the pathogenesis of HP …

Pharmacokinetic And Pharmacodynamic Studies Of A Novel Spectinamide Series Of Antituberculosis Agents, V. N. R. Pavan Kumar Vaddady

Theses and Dissertations (ETD)

Spectinamides are novel amide derivatives of the antibiotic spectinomycin that have emerged as a new class of agents to treat tuberculosis. These agents showed potent in vitro activity against Mycobacterium tuberculosis (MTB) compared to spectinomycin and in a preliminary in vivo study in interferon gamma (IFN‑γ) knockout mice, spectinamide Lee1329 reduced the lung bacillary load of TB comparable to streptomycin. We hypothesized that the application of an iterative pharmacokinetics and pharmacodynamics (PK/PD) guided approach would facilitate the optimization of these lead compounds suitable for further development.

A series of in vitro experiments including parallel artificial membrane permeability assay (PAMPA), microsomal …