Bacterial Infections and Mycoses Commons^™

Harnessing Antagonistic Pleiotropy: Tolc-Dependent Coliphages Can Drive Reduced Antibiotic Resistance In E. Coli, Cooper Mckenna

CMC Senior Theses

The rise of multidrug-resistant (MDR) bacterial pathogens has been a growing concern in healthcare around the world, and bacteriophage (phage) therapy is a promising method to combat MDR infections. One defense mechanism of E. coli against antibiotics is the TolC-AcrAB efflux pump. At the same time, some phages use TolC as a surface receptor to infect the cell. This puts TolC at a crossroads in which it is beneficial to the bacteria to protect against antibiotics but harmful by allowing phage infection, creating the potential for evolutionary trade-offs. Previous research has identified only three TolC-dependent phages and shown phage-resistant E. …

Novel Engineering Approaches For Orthopedic Injury Treatment And Infection Diagnosis, Cynthia Co

Bioengineering Dissertations - Archive

Bioengineering has made significant contributions to the treatment of orthopedic injury through interdisciplinary approaches. Central to these advancements are many orthopedic implants, including anchors and joint replacements, which have been designed to restore mobility. Despite their functional efficacy, these products have limited lifespan and are associated with many complications, such as implant-associated infection. The success of implant design and function, both in the short and long term, is paramount for enhancing patient outcomes and overall well-being. Therefore, my thesis work is dedicated to addressing these critical challenges, aiming to maximize their treatment effect while minimizing the implant-associated complications.

Long-term patient …

Tiny But Mighty, An Exploration Of Microbes And Plants As Sources Of Small Novel Bioactive Compounds Against Invasive Mycoses., Hannah Mai Peacock, James Anthony O'Connor

SURE Journal: Science Undergraduate Research Experience Journal

Despite the high mortality rate involved with invasive cerebral mycoses, there is a relative lack of research available around antifungals capable of crossing the blood brain barrier.

In this study the metabolites of four plants (Crocus vernus, Miniature Narcissus (daffodil), Osmanthus delavayi and Taraxacum officinale (common dandelion)) and two bacteria (Lacticaseibacillus paracasei and Staphylococcus epidermidis) were extracted and assayed for antifungal activity against Candida albicans and Saccharomyces cerevisiae. Thin layer chromatography and bioautography were then employed to assess the activity of the constituent components of sources showing antifungal activity.

Metabolites of S.epidermidis, and extracts …

The Discovery, Characterization, And Engineering Of Autolytic Enzymes As Antimicrobials, Jacob M. Furlon

Dartmouth College Ph.D Dissertations

In an age of rising levels of antibiotic resistance, we are quickly running out of tools to address some of the most virulent and widespread infectious bacteria. One group of enzymes that show significant potential for use as next-generation antibiotics are antimicrobial peptidoglycan hydrolases, often referred to as lysins. These enzymes are responsible for the breakdown of peptidoglycan within the bacterial cell wall, and, when exogenously applied, can result in dramatic destabilization of the cell wall leading to rapid lysis of the bacteria. While phage endolysins have been widely investigated as potential antimicrobials, the therapeutic potential of endogenous autolysins from …

Additive Effects Of Cyclic Peptide [R4w4] When Added Alongside Azithromycin And Rifampicin Against Mycobacterium Avium Infection, Melissa Kelley, Kayvan Sasaninia, Arbi Abnousian, Ali Badaoui, James Owens, Abrianna Beever, Nala Kachour, Rakesh Kumar Tiwari, Vishwanath Venketaraman

Pharmacy Faculty Articles and Research

Mycobacterium avium (M. avium), a type of nontuberculous mycobacteria (NTM), poses a risk for pulmonary infections and disseminated infections in immunocompromised individuals. Conventional treatment consists of a 12-month regimen of the first-line antibiotics rifampicin and azithromycin. However, the treatment duration and low antibiotic tolerability present challenges in the treatment of M. avium infection. Furthermore, the emergence of multidrug-resistant mycobacterium strains prompts a need for novel treatments against M. avium infection. This study aims to test the efficacy of a novel antimicrobial peptide, cyclic [R4W4], alongside the first-line antibiotics azithromycin and rifampicin in reducing M. avium survival. Colony-forming unit (CFU) …

Elucidating The Impact Of Sos-Response Timing In On Escherichia Coli Survival Following Treatment With Fluoroquinolone Topoisomerase Inhibitors, Stephanie Schofield

Honors Scholar Theses

Antibiotic treatment failure is a public health crisis, with a 2019 report stating that roughly 35,000 deaths occur in the United States yearly due to bacterial infections that are unresponsive to antibiotics (1). One complication in the treatment of bacterial infection is antibiotic persistence which further compromises our battle to effectively treat infection. Bacterial persisters can exist in clonal bacterial cultures and can tolerate antibiotic treatment by undergoing reversible phenotypic changes. They can survive drug concentrations that their genetically identical kin cannot. Some persisters remain in a slow growing state and are difficult to target with current antibiotics. A specific …

Characterization Of Antibiotic Susceptibility Profiles Of Extensively- And Pan-Drug Resistant Acinetobacter Baumannii Clinical Isolates, Rachel Carr, Justin Halim, Rebecca Fliorent, Henry Fraimow, Dejan Nikolic, Valerie Carabetta

Rowan-Virtua Research Day

Acinetobacter baumannii is an opportunistic pathogen common in intensive care units (ICUs), particularly among immunocompromised individuals. Nosocomial A. baumannii infections have become increasingly problematic in recent years, as these bacteria rapidly acquire antibiotic resistance, leading to the emergence of multidrug, extensively drug and pan drug-resistant (MDR, XDR, and PDR, respectively) isolates. Recently, Cooper University Hospital (CUH) experienced a large increase in highly drug-resistant A. baumannii infections, which had a mortality rate of 60%. Oftentimes, physicians had to turn to combinations of drugs with no experimental verification or historically shelved antibiotics, such as the polymyxins, in a desperate attempt to save …

Investigating The Antibacterial And Immunomodulatory Properties Of Lactobacillus Acidophilus Postbiotics, Rachael M. Wilson

Graduate School of Biomedical Sciences Theses and Dissertations

Probiotics are nonpathogenic microorganisms that have been extensively studied for their ability to prevent various infectious, gastrointestinal, and autoimmune diseases. The mechanisms underlying these probiotic effects have not been elucidated. However, we and other researchers have evidence suggesting that probiotic bacteria secrete metabolites that are antimicrobial and anti-inflammatory. As such, we developed a methodology to collect the secreted metabolites from a probiotic bacterium, Lactobacillus acidophilus, and tested this cell free filtrate (CFF) both in vitro and in vivo. Using this CFF, we have demonstrated that L. acidophilus secretes a molecule(s) that has specific bactericidal activity against the opportunistic pathogen, Pseudomonas …

Radioluminescence Based Biochemical Sensing And Imaging Strategies To Measure Local Drug Release And Ph, Gretchen B. Schober

All Dissertations

In this dissertation we describe methods for measuring infection relevant biochemical analytes using radioluminescent and ultrasound luminescent materials. Films and nanoparticles fabricated with europium doped gadolinium oxysulfide (Gd₂O₂S:Eu³⁺) are used to quantitatively measure radiolabeled pharmaceutical concentration, specifically tritium labeled vancomycin (³H-vancomycin). Europium and dysprosium doped strontium aluminate is used to fabricate an ultrasound modulated, pH sensing film. These methods are indicated for theranostic evaluation of implant associated infection. Bacterial biofilms are inherently resistant to traditional antibiotic treatment and can coat biomedical implants. These biofilm related infections are difficult or impossible to eradicate …

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 …

Safety And Efficacy Of Silver-Coated Biomaterials In Vivo, Megan Klem, Darien L. Seidman, Rahyan Mahmoud, Manuella Adu, Lei Yu, Jeffrey Hettinger, Renee M Demarest

Rowan-Virtua Research Day

Overtreatment and overuse of antibiotics in healthcare and agricultural settings have contributed to the selective pressure on bacterial strains to develop resistance. Resistance can develop as a result of mutations and subsequent resistance genes that allow bacteria to survive against antibiotics. Novel silver-oxide coatings were developed and were previously demonstrated to prevent adhesion of gram-negative bacteria (Escherichia Coli and Pseudomonas Aeruginosa) to the disc, but did not prevent gram-positive bacterial adherence (Streptococcus Aureus). In order to determine whether the silver-oxide coatings are bacterial static and may be preventing progression to biofilm formation, in vivo analysis of S. Aureus attached to …

Effectiveness Of Stabilized Hypochlorous Acid In Acute Peritonitis Treatment: A Murine Surgical Study, Benjamin Michael Pomeroy

Graduate Theses/Dissertations

Peritonitis is an inflammatory condition affecting the mesothelial cells that line the peritoneal cavity and is commonly induced by bowel perforations. This medical emergency is treated through antibiotic therapy and surgical intervention followed by tissue irrigation (lavage). Acute treatments aim to remove the bacterial burden, however recurring peritoneal infections occur at high rates and contribute to patient morbidity. These recurring infections are likely due to the inability of lavage solutions to remove the entire massive intra-abdominal bacterial load due to intestinal perforation. Numerous antiseptic solutions and antibiotic additives have been evaluated in their ability to improve source control by abdominal …

Eradication Of Enterococcus Faecalis In Conventional Endodontic Retreatments (A Randomized Clinical Trial), Fadl H. Khaled, Roula S. Abiad, Khaled Abd El Galil, Essam Osman

BAU Journal - Creative Sustainable Development

Enterococcus faecalis is the most common bacteria isolated in conventional endodontic retreatments. Aim: To compare the impact of three irrigation modalities on the elimination of the isolated microbial strains of Enterococcus faecalis. Materials and Methods: Thirty patients requiring conventional endodontic retreatment for one of their mandibular premolars and tested positive for E. faecalis were chosen. Patients were randomly divided into three groups (n=10) according to the irrigation modality to be used; group I: syringe irrigation (NaOCl 2.625%), group II: NaOCl 2.625%+EndoActivator and group III: NaOCl 2.625%+diode laser. Before obturation, samples S2 were collected and PCR analysis was performed to identify …

Formulation Of Coffee Extract As Polymeric Nanoparticles And Studying Their Potential Biological Activities, Nouran Sharaf

Theses and Dissertations

Coffee extract was prepared and optimized (by solvent extraction) and subsequently entrapped into PLGA nanoparticles using single emulsion-solvent evaporation method (using Design Expert software). Dynamic Light Scattering, Scanning Electron Microscope, Fourier Transform-Infrared Spectroscopy and Folin Ciocalteau assay were used to characterize the NPs and to aid in selecting the optimum formulation conditions. The optimized NPs were in-vitro evaluated for their antimicrobial (by agar-well diffusion method), antioxidant (by DPPH assay) and anticancer (by MTT assay) activities. Finally, the release rate study was conducted for the NP sample showing the highly promising results.

The succeeded NP sample, in terms of the most …

Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Tools And Antimicrobial Agents, David Salehi

Pharmaceutical Sciences (MS) Theses

Cell-penetrating peptides containing arginine as positively charged residues and tryptophan or diphenylalanine as hydrophobic residues were synthesized. The synthesis was accomplished through the Fmoc solid-phase peptide synthesis in the presence of HBTU and DIPEA. The side-chain protected linear peptides were cleaved from the resin and cyclized in the presence of DIC and HOAt in the solution phase overnight. MALDI-TOF mass spectrometry was used to characterize the peptides.

The cytotoxicity of the synthesized peptides was determined in CCRF-CEM (human, lymphoblast peripheral blood), and HEK-293 (human, embryonic epithelial kidney healthy) cells using the MTS assay. A concentration of 10 µM was found …

Therapeutic Drug Monitoring Of Beta-Lactam Antibiotics In Critically Ill Patients With Sepsis, Melissa Thompson Bastin

Theses and Dissertations--Clinical and Translational Science

Sepsis is a devastating diagnosis affecting over 750,000 patients a year, accounting for approximately 10% of all hospital admissions, costs more than $50,000 per patient, and exceeds $17 billion annual spending. The mortality rate for sepsis remains unacceptably high: one out of every three patients diagnosed with sepsis dies. Sepsis physiology induces physiologic changes to drug pharmacokinetic (PK) parameters that alter the ability to achieve the goal pharmacodynamic (PD) target for beta-lactams of >4-fold unbound concentration above the minimum inhibitory concentration for 100% of the dosing interval (100% fT >4x MIC). Sepsis treatment such as volume resuscitation and vasopressor …

Risk Factors And Trends In Antimicrobial Susceptibility Patterns In Strains Of Neisseria Gonorrhoeae Following Changes In The Cdc Sexually Transmitted Disease (Std) Treatment Guidelines – United States, 2012-2018, Niketta A. Womack

College of Graduate Studies: Theses & Dissertations

Antimicrobial resistant Neisseria gonorrhoeae (N. gonorrhoeae) has become a major global public health concern in the 21st century. Surveillance activities are essential in identifying risk factors in priority populations. The purpose of this study was to identify risk factors associated with and trends in antimicrobial susceptibility patterns in N. gonorrhoeae strains identified through the Gonococcal Isolate Surveillance Project (GISP). A study sample of 37,157 men was evaluated to measure adherence to changes in CDC’s STD treatment guidelines in 2012 and 2015. Data were analyzed to measure associations between independent and dependent variables by conducting bivariate and logistic regression …

Impact Of A Pharmacist-Driven Methicillin-Resistant Staphylococcus Aureus Nasal Swab Protocol On The De-Escalation Of Empiric Vancomycin In The Setting Of Community Acquired Pneumonia, Grether Hernandez Gama, Winifred Pardo, Wilbert Fuerte, James Adefisoye

All Publications

No abstract provided.

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 …

Cyclic Peptide [R4w4] In Improving The Ability Of First-Line Antibiotics To Inhibit Mycobacterium Tuberculosis Inside In Vitro Human Granulomas, Joshua Hernandez, David Ashley, Ruoqiong Cao, Rachel Abrahem, Timothy Nguyen, Kimberly To, Aram Yegiazaryan, Ajayi Akinwale David, Rakesh Kumar Tiwari, Vishwanath Venketaraman

Pharmacy Faculty Articles and Research

Tuberculosis (TB) is currently one of the leading causes of global mortality. Medical non-compliance due to the length of the treatment and antibiotic side effects has led to the emergence of multidrug-resistant (MDR) strains of Mycobacterium tuberculosis (M. tb) that are difficult to treat. A current therapeutic strategy attempting to circumvent this issue aims to enhance drug delivery to reduce the duration of the antibiotic regimen or dosage of first-line antibiotics. One such agent that may help is cyclic peptide [R₄W₄], as it has been shown to have antibacterial properties (in combination with tetracycline) …

Chrysin‐Loaded Chitosan Nanoparticles Potentiates Antibiofilm Activity Against Staphylococcus Aureus, Busi Siddhardha, Uday Pandey, K. Kaviyarasu, Rajasekharreddy Pala, Asad Syed, Ali K. Bahkali, Abdallah M. Elgorban

Pharmacy Faculty Articles and Research

The application of nanotechnology in medicine is gaining popularity due to its ability to increase the bioavailability and biosorption of numerous drugs. Chrysin, a flavone constituent of Orocylumineicum vent is well‐reported for its biological properties. However, its therapeutic potential has not been fully exploited due to its poor solubility and bioavailability. In the present study, chrysin was encapsulated into chitosan nanoparticles using TPP as a linker. The nanoparticles were characterized and investigated for their anti‐biofilm activity against Staphylococcus aureus. At sub‐Minimum Inhibitory Concentration, the nanoparticles exhibited enhanced anti‐biofilm efficacy against S. aureus as compared to its bulk counterparts, chrysin …

Antifungal Defense Molecules From Bacterial Symbionts Of North American Trachymyrmex Ants, Georgia Scherer

CMC Senior Theses

Defensive symbioses, in which microbes provide molecular defenses for an animal host, hold great potential as untapped sources of therapeutically useful antibiotics. Fungus-growing ants use antifungal defenses from bacterial symbionts to suppress pathogenic fungi in their nests. Preliminary chemical investigations of symbiotic bacteria from this large family of ants have uncovered novel antifungal molecules with therapeutic potential, such as dentigerumycin and selvamicin.

In this study, the bacterial symbionts of North American Trachymyrmex fungus-growing ants are investigated for antifungal molecules. Plate-based bioassays using ecologically-relevant fungal pathogens confirmed that these bacteria have antifungal activity. In order to purify and identify the antifungal …

Determining The Antibacterial Activity And Mode Of Action Of Tirandamycin, Hailey Bouchard

CMC Senior Theses

Tirandamycin is a small molecule natural product that has been isolated from various species of marine and terrestrial Streptomyces. The natural product has shown antibacterial activity against an array of Gram-positive and Gram-negative bacteria, showing promise as a pharmaceutical drug. Tirandamycin has 14 known derivatives, many of which have been created synthetically. Some of its derivatives are particularly potent against the high-risk bacteria vancomycin-resistant Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae and Escherichia coli. However, the antibacterial potency of these derivatives has not been tested systematically leading to the possibility of discovering more potent …

Optimizing Antibiotic Management Of Pediatric Acute Otitis Media In An Emergency Department, Alicia Daggett, Alaina N. Burns, Brian R. Lee, Nirav Shastri, Patricia Phillips, Rana E. El Feghaly

Posters

Problem

Children diagnosed with acute otitis media (AOM) at the Children's Mercy Hospital Kansas Emergency Department routinely get antibiotic prescriptions. There is rarely discussion with families about watchful waiting (defined as discussion of observation with parents and providing a safety-net antibiotic prescription that parents can ill if the patient is not improving or is worsening over the next 48 hours).

The aim of this quality improvement project is to increase watchful waiting for AOM at the CMK ED by 20% by March 2020, with an overall goal of decreasing antibiotic use for AOM.

The Wet Bridge Transfer System: An Novel In Vitro Tool For Assessing Exogenous Surfactant As A Pulmonary Drug Delivery Vehicle, Brandon J. Baer

Western Research Forum

Background:

Due to its complex branching structure, direct drug delivery to the remote areas of the lung is a major challenge. Consequently, most therapies, such as those treating pulmonary infection and inflammation, must utilize large systemic dosing, with the potential for adverse side effects. A novel alternative strategy is to use exogenous surfactant, a material capable of distributing throughout the lung, as a pulmonary drug delivery vehicle.

Objective:

Utilize an in vitro transferring system to assess exogenous surfactant (BLES) as a pulmonary delivery vehicle for different therapeutics.

Methods:

An in vitro technique was developed to simultaneously study surfactant delivery and …

Impact Of A Urinary Tract Infection Treatment Pathway On Antimicrobial Prescribing Within A Community Hospital, Alyssa Donadio, Heidi Clarke, Erika Dittmar

All Publications

No abstract provided.

Azithromycin For Early Pseudomonas Infection In Cystic Fibrosis. The Optimize Randomized Trial., Nicole Mayer-Hamblett, George Retsch-Bogart, Margaret Kloster, Frank Accurso, Margaret Rosenfeld, Gary Albers, Philip Black, Perry Brown, Annemarie Cairns, Stephanie D. Davis, Gavin R. Graff, Gwendolyn S. Kerby, David Orenstein, Rachael Buckingham, Bonnie W. Ramsey, Optimize Study Group

Manuscripts, Articles, Book Chapters and Other Papers

RATIONALE: New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach that complements traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation and inflammation may ultimately prolong the time to Pa recurrence.

OBJECTIVES: To test the hypothesis that the addition of azithromycin to TIS in children with cystic fibrosis and early Pa decreases the risk of pulmonary exacerbation and prolongs the time to Pa recurrence.

METHODS: The OPTIMIZE (Optimizing Treatment for Early Pseudomonas aeruginosa Infection in Cystic Fibrosis) trial was a multicenter, double-blind, randomized, placebo-controlled, 18-month trial …

Design, Synthesis, And Evaluation Of Amphiphilic Cyclic And Linear Peptides Composed Of Hydrophobic And Positively-Charged Amino Acids As Antibacterial Agents, Neda Riahifard, Saghar Mozaffari, Taibah Aldakhil, Francisco Nunez, Qamar Alshammari, Saud Alshammari, Jason Yamaki, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Antimicrobial peptides (AMPs) contain amphipathic structures and are derived from natural resources. AMPs have been found to be effective in treating the infections caused by antibiotic-resistant bacteria (ARB), and thus, are potential lead compounds against ARB. AMPs’ physicochemical properties, such as cationic nature, amphiphilicity, and their size, will provide the opportunity to interact with membrane bilayers leading to damage and death of microorganisms. Herein, AMP analogs of [R₄W₄] were designed and synthesized by changing the hydrophobicity and cationic nature of the lead compound with other amino acids to provide insights into a structure-activity relationship against selected …

Interfering With Dna Decondensation As A Strategy Against Mycobacteria, Enzo M. Scutigliani, Edwin R. Scholl, Anita E. Grootemaat, Sadhana Khanal, Jakub A. Kochan, Przemek M. Krawczyk, Eric A. Reits, Atefeh Garzan, Huy X. Ngo, Keith D. Green, Sylvie Garneau-Tsodikova, Jan M. Ruijter, Henk A. Van Veen, Nicole N. Van Der Wel

Pharmaceutical Sciences Faculty Publications

Tuberculosis is once again a major global threat, leading to more than 1 million deaths each year. Treatment options for tuberculosis patients are limited, expensive and characterized by severe side effects, especially in the case of multidrug-resistant forms. Uncovering novel vulnerabilities of the pathogen is crucial to generate new therapeutic strategies. Using high resolution microscopy techniques, we discovered one such vulnerability of Mycobacterium tuberculosis. We demonstrate that the DNA of M. tuberculosis can condense under stressful conditions such as starvation and antibiotic treatment. The DNA condensation is reversible and specific for viable bacteria. Based on these observations, we hypothesized …

Infections Not Fought: Antibiotic Resistance In Underserved Communities, Derek Lillestolen

Senior Honors Theses

In 1928, the profound effects of penicillin were discovered and antibiotic treatments became extremely popular. Broad-spectrum antibiotics, like tetracyclines, have been since branded as cure-all prescriptions and used profusely in the Western World and abroad. Due to ignorance of specific biochemical mechanisms and the misuse of antibiotics these drugs inadvertently allowed the rise in prevalence of antibiotic resistant strains of certain bacteria as the century progressed. Now, the specific genetic causes and mechanisms of antibiotic resistance are being understood, but the fight against antimicrobial resistance is far from over. In the United States, thousands of fatalities are caused annually by …