Digital Commons Network^™

Utility Of Combination Antimicrobial Therapy In Adults With Bloodstream Infections Due To Enterobacteriaceae And Non-Fermenting Gram-Negative Bacilli Based On In Vitro Analysis At Two Community Hospitals, Rachel Foster, Casey Troficanto, P. Brandon Bookstaver, Joseph Kohn, Julie Ann Justo, Majdi Al-Hasan

Faculty Publications

This study examined the utility of combination therapy for bloodstream isolates of Enterobacteriaceae and non-fermenting Gram-negative bacilli (NFGN) from adults at two community hospitals from January 2010 through to June 2015. Changes to in vitro antimicrobial susceptibilities by adding ciprofloxacin or gentamicin to third-generation cephalosporins (3GC) were examined overall and in patients with risk factors for 3GC resistance. Overall ceftriaxone susceptibility among Enterobacteriaceae was 996/1063 (94%) and 247/295 (84%) in patients with 3GC resistance risk factors. Susceptibilities increased marginally by adding ciprofloxacin or gentamicin (mean difference 2.4% (95% CI 1.5, 3.4) and 3.0% (95% CI 2.0, 4.0), respectively, overall and …

Development Of A Novel Loop-Mediated Isothermal Amplification Method To Detect Guiana Extended-Spectrum (Ges) Β-Lactamase Genes In Pseudomonas Aeruginosa, Chika Takano, Mitsuko Seki, Dong Wook Kim, Humphrey Gardner, Robert E. Mclaughlin, Paul E. Kilgore, Kazunari Kumasaka, Satoshi Hayakawa

Department of Pharmacy Practice

Infections caused by multidrug-resistant Pseudomonas aeruginosa in hospitalized patients are often fatal, and nosocomial infections caused by Guiana extended-spectrum (GES) β-lactamase-producing strains are of growing concern. Several genotypes of the GES β-lactamase gene (bla_GES) include a single missense mutation, a change from G to A at nucleotide position 493 (G_493A) that changes glycine to serine; the mutant enzyme exhibits carbapenemase activity. Rapid and reliable identification of drug-resistance is important in clinical settings; however, culture methods remain the gold standard. Conventional and real-time PCR cannot identify carbapenemase-producing genotypes, and direct DNA sequencing is essential. We established …

Carbapenem-Resistant Enterobacteriaceae Infections: A Review Of Epidemiology And Treatment Options, Julie Harting

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Daptomycin Dosing In Obese Patients: Analysis Of The Use Of Adjusted Body Weight Versus Actual Body Weight, Ashley N. Fox, Winter J. Smith, Katherine E. Kupiec, Stephanie J. Harding, Beth H. Resman-Targoff, Stephen B. Neely, Bryan P. White, Ryan E. Owens

Pharmacy Faculty Publications and Presentations

Background: Food and Drug Administration-approved daptomycin dosing uses actual body weight, despite limited dosing information for obese patients. Studies report alterations in daptomycin pharmacokinetics and creatine phosphokinase elevations associated with higher weight-based doses required for obese patients. Limited information regarding clinical outcomes with alternative daptomycin dosing strategies in obesity exists. Objective: This study evaluates equivalency of clinical and safety outcomes in obese patients with daptomycin dosed on adjusted body weight versus a historical cohort using actual body weight. Methods: This retrospective, single center study compared equivalency of outcomes with two onesided tests in patients with body mass index >30 kg/m2 …

Biosynthetic And Synthetic Strategies For Assembling Capuramycin-Type Antituberculosis Antibiotics, Ashley L. Biecker, Xiaodong Liu, Jon S. Thorson, Zhaoyong Yang, Steven G. Van Lanen

Pharmaceutical Sciences Faculty Publications

Mycobacterium tuberculosis (Mtb) has recently surpassed HIV/AIDS as the leading cause of death by a single infectious agent. The standard therapeutic regimen against tuberculosis (TB) remains a long, expensive process involving a multidrug regimen, and the prominence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) strains continues to impede treatment success. An underexplored class of natural products—the capuramycin-type nucleoside antibiotics—have been shown to have potent anti-TB activity by inhibiting bacterial translocase I, a ubiquitous and essential enzyme that functions in peptidoglycan biosynthesis. The present review discusses current literature concerning the biosynthesis and chemical synthesis of capuramycin …

Plasmodium Para-Aminobenzoate Synthesis And Salvage Resolve Avoidance Of Folate Competition And Adaptation To Host Diet, Joachim Michael Matz, Mutsumi Watanabe, Mofolusho Falade, Takayuki Tohge, Rainer Hoefgen, Kai Matuschewski

Pharmaceutical Sciences Faculty Publications

Folate metabolism is essential for DNA synthesis and a validated drug target in fast-growing cell populations, including tumors and malaria parasites. Genome data suggest that Plasmodium has retained its capacity to generate folates de novo. However, the metabolic plasticity of folate uptake and biosynthesis by the malaria parasite remains unresolved. Here, we demonstrate that Plasmodium uses an aminodeoxychorismate synthase and an aminodeoxychorismate lyase to promote the biogenesis of the central folate precursor para-aminobenzoate (pABA) in the cytoplasm. We show that the parasite depends on de novo folate synthesis only when dietary intake of pABA by …

Assessing Risk Factors For Esophageal Cancer, Mahadev Rao Dr

Manipal College of Pharmaceutical Sciences, Manipal Theses and Dissertations

Background: Esophageal cancer (EC) stands the 6th most frequent cause of death due to cancer worldwide.It is mainly classified into mainly Esophageal squamous cell carcinoma (ESCC) and Esophageal adenocarcinoma (EAC). The incidence extends from Eastern to Central Asia. Although there are advances in the management and treatment of EC patients, the generaloutcome is very poor. It is mainly because of the diagnosis during its advanced stages and due to the absence of early clinical symptoms. Therefore, it is an important health challenge .A clear picture regarding the risk factors and other patient demographics may help to improve the management of …

Role Of Cytochrome P450 2b6 Polymorphisms In Unexpected Methadone Death, Taha Ahmad

Theses, Dissertations and Capstones

Methadone is a synthetic, long-acting opioid prescribed as an analgesic for chronic pain. It has a single chiral center forming two enantiomers, (R)-methadone and (S)-methadone, each having specific pharmacological actions. Concentrations of (R)- and (S)-methadone above therapeutic levels have the ability to cause serious, life-threatening, and fatal side effects. Cardiotoxicity is caused by elevated (S)-methadone levels by prolonging the QT interval of the heart’s electrical cycle. In 2014, methadone accounted for only 1% of all opioids prescribed for pain, but was responsible for 3,400 of the 14,838 individuals (~23%) who died in the United States from overdoses due to prescription …

College Of Pharmacy 2019, Nova Southeastern University

Health Professions Divisions Course Catalogs and Course Descriptions

No abstract provided.

The Protective Role Of Estrogen On Hiv-1 Mediated Neurotoxicity, Macklin Licamied

Honors Theses

The prevalence of HIV among men have been in a steady inclination over the last several decades, yet the accelerated infection rate among older women is considerably concerning. Not only does the HIV virus affect the immune system but it also affects the central nervous system. One of its viral proteins, Tat, acts as an excitotoxin and disrupts the cell’s membrane potential by increasing the concentration of Ca2+ inside the cell. This influx of calcium ions leads to apoptosis and secretion of the cell’s contents into the surrounding area. Macrophages, along with other innate immune components, gather and induce the …

Development Of A Novel Nanotechnology-Based Vaccine Adjuvant And Delivery System For Systemic And Mucosal Immunity, Mohammed Ali Bakkari

Electronic Theses and Dissertations

Many serious infections for which there are no existing vaccines, enter by a mucosal route such as HIV, influenza, and tuberculosis, etc. Therefore, designing safe and effective mucosal vaccines that elicit robust immune response at mucosal sites is still a major challenge without a safe mucosal adjuvant. Previously, our laboratory had discovered inulin acetate as a novel toll-like-receptor-4 agonist (adjuvant). The study in this dissertation explored the application of nanoparticles prepared with inulin acetate (InAc-NPs) as a vaccine adjuvant and delivery system for enhancing mucosal immunity. The rationale behind selecting InAc-NPs is their proven ability to activate strong systemic immunity …

Comparison Of Patient Outcomes In A Pharmacist-Led Outpatient Parenteral Antimicrobial Therapy Program, Zachary Howe

Undergraduate Honors Thesis Collection

Purpose: Outpatient parenteral antimicrobial therapy (OPAT) is a therapeutic option meant to conserve healthcare resources when treating infections requiring the administration of IV antibiotics over a prolonged treatment course. In November 2016 at Franciscan Alliance Indianapolis, a dedicated pharmacist was hired to build a formal OPAT program for all patients discharged on IV antimicrobials under the care of the infectious disease physician group. The number of “good catch” events observed since the program’s formal inception has encouraged the creation of this study designed to examine the impact of this program on patient outcomes and antimicrobial stewardship.

Methods: This was a …

Comparative Characteristics Of Antibacterial Activity Of Plants Growing In The Central Part Of The Republic Of Tajikistan., Saidbeg Satorov, F. Mirzoeva, Sh. Satorov, M. Vakhidova, Vyacheslav Dushenkov

Publications and Research

Objective: To evaluate the spectrum of antibacterial activity of plants growing in the central part of the Republic of Tajikistan.
Methods: The antibacterial properties of 18 plant species from the 14 families were studied. The extract samples on dry filter discs were prepared according to the method developed at Rutgers University. Screens-to-Nature (STN) and disc diffusion (DD) methods were used to assess antimicrobial properties of the extracts. The antimicrobial activity of plant extracts was determined against four types of pathogenic standard museum strains of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, as well as …

Regulatory Gaps In Drug Compounding: Implications For Patient Safety, Innovation, And Fraud, Joanna Shepherd

Faculty Articles

Drug compounding is the practice of mixing, combining, or altering drug ingredients to create a product that meets the medical needs of a patient whose needs cannot otherwise be met with commercially-available products. Compounding is essential for patients that are allergic to certain ingredients or cannot tolerate the route of administration or dosage form of a commercially-available drug. Compounding may also enable pharmacists to supply medications when there is a shortage of commercially-available drugs. For example, amid the nationwide shortage of generic liquid Tamiflu and growing flu deaths in early 2018, pharmacists around the country used Tamiflu capsules to compound …

Study Of Pharmacist Workforce In Public Sector, Of Republic Of The Union Of Myanmar, Lwin Nyein Aye

Chulalongkorn University Theses and Dissertations (Chula ETD)

Health workforce shortage was common across the world including Myanmar. However, there was not previous study about the pharmacist workforce to ascertain the shortage problem in Myanmar. This study was aimed to analyze the current situation of pharmacist workforce in Myanmar especially in public sector and to construct a simulation model to suggest the appropriate policy options to the policymakers in improving the pharmacist workforce situations in the public hospitals.For the first objective, the study design was a cross-sectional survey using a mixed method which consisted of the secondary data analysis and semi-structured face-to-face interviews. The government registry data related …

Progress Toward The Synthesis Of 3-Methoxyflavones As Potential Antioxidants, Neuroprotective Agents, And Trifluoromethylated 19f Nmr Probes, Reem Alkhodier

Electronic Theses and Dissertations

The total synthesis of polyhydroxylated flavones have proven to be challenging, due to the presence of more than one hydroxyl group. Direct cyclization was not successful in any of the attempts. However, by using a silyl protecting group, the cyclization was feasible. Other reactions like the Friedel-Crafts acylation and selective protection of phenols were also difficult.

Design Of Thermosensitive Hydrogel For Extended-Release Of Praziquantel, Sheng Feng

Electronic Theses and Dissertations

Parasitic diseases are a severe threat to people and animals. Praziquantel is the most comanti-parasitic drug with high efficiency, and it has been used to treat parasitic diseases for many years. However, it has very strong gastrointestinal and liver metabolism that leads to a strong first-pass effect and a short half-life. Additionally, the frequent oral administration was inconvenient for the large livestock. To overcome these drawbacks, this study aimed to develop an extended-release thermosensitive hydrogel formulation that was applicable to the injectable administration. The praziquantel-loaded hydrogel formulation based on poloxamer 407 (20%, w/v) was prepared, and two strategies for modifications …

Carbapenem-Resistant Enterobacteriaceae: Epidemiology, Genetics, In Vitro Activity, And Pharmacodynamic Modeling, Brandon Kulengowski

Theses and Dissertations--Pharmacy

Background: Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) such as Escherichia coli and Klebsiella pneumoniae are among the most urgent threats of the infectious disease realm. The incidence of these infections has been increasing over the years and due to very limited treatment options, mortality is estimated at about 50%. By 2050, mortality from antimicrobial resistant infections is expected to surpass cancer at 10 million deaths annually.

Methods: We evaluated 18 contemporary antimicrobials against 122 carbapenem-resistant Enterobacteriaceae using a variety of antimicrobial susceptibility testing methods according to Clinical Laboratory Standards Institute guidelines. Time-kill studies were performed on clinical isolates with variable …

Pharmacokinetic And Pharmacodynamic Evaluation Of Cocaine Hydrolases For The Treatment Of Cocaine Overdose And Cocaine Addiction Using Rodent Models, Xirong Zheng

Theses and Dissertations--Pharmacy

Overdose and addiction are two medical complications of cocaine abuse. To date, there is no FDA approved pharmacotherapy specific for cocaine abuse. Cocaine hydrolases (CocHs) have been extensively investigated for its potential in anti-cocaine therapy. Previous studies have demonstrated that CocHs efficiently hydrolyze cocaine to generate biologically inactive metabolites both in vivo and in vitro. However, it has not been studied whether there is gender difference in the therapy using CocHs. In addition, the effectiveness of CocHs is unknown for treating cocaine toxicity when alcohol is co-administered.

The main purpose of this dissertation is to characterize and evaluate efficient …

Impact Of Area-Under-The-Curve Monitoring For Vancomycin On Incidence Of Acute Kidney Injury In Orthopedic Patients, Kelli R. Keats

MPA/MPP/MPFM Capstone Projects

Vancomycin is an antibiotic used regularly in hospitals across the world. The most concerning adverse effect of vancomycin is its documented effect on kidney function. This study examines the impact of two dosing strategies of vancomycin on patients’ kidney function at the University of Kentucky Albert B. Chandler Medical Center. It specifically focuses on patients on the orthopedic service because these patients traditionally receive higher doses of vancomycin for longer periods of time due to the severity of their infections, which puts them at an increased risk of vancomycin-induced nephrotoxicity compared to other patients.

This study will serve as a …

The Role Of Sex Hormones On Monocarboxylate Transporter Expression In Tissues Related To Drug Disposition, Jieyun Cao

University of the Pacific Theses and Dissertations

Proton- and sodium-dependent monocarboxylate transporters (MCTs (SLC16A) and SMCTs (SLC5A)) transport monocarboxylates such as ketone bodies, lactate and pyruvate, as well as drugs such as gamma-hydroxybutyric acid. CD147 acts as an ancillary protein for MCT1 and MCT4, and is involved in membrane trafficking. Previously, it has been shown that MCT expression changes under different sex hormone conditions in skeletal muscle and Sertoli cells. However, it is unknown if MCTs, SMCTs or CD147 demonstrate sex differences in tissues where they play an important role in drug disposition. Monocarboxylate transporter substrates GHB and valproic acid have demonstrated sex differences in pharmacokinetic profiles. …

Evaluation Of An Outpatient Parenteral Antimicrobial Therapy Program In A Specialty Clinic Setting, Elizabeth Hauk

Undergraduate Honors Thesis Collection

Introduction: Outpatient parenteral antimicrobial therapy (OPAT) has gained popularity since its first description in 1974. At Community Health Network (CHN), the OPAT clinic was developed three years ago by an ambulatory care clinical pharmacist and includes pharmacist driven monitoring for all patients receiving OPAT. The pharmacist ensures labs are drawn weekly to assess for renal or hepatic function changes, medication levels are drawn and adjusted as needed, and repeat labs and levels are ordered to continue assessing therapy. There have not been any studies to date to investigate CHN’s OPAT program both demographically and clinically.

Objectives: The primary objective of …

Hiv With Opportunistic Neuroinfection, Rahul Vyas, Rajendra Prasad

Digital Journal of Clinical Medicine

No abstract provided.

Development Of Bivalent Ligands Targeting The Putative Mu Opioid Receptor And Chemokine Receptor Cxcr4 Heterodimer, Bethany A. Reinecke

Theses and Dissertations

Human immunodeficiency virus (HIV) and opioid abuse have been described as synergistic epidemics. Pharmacologically, it has been found that opioids have the capacity to enhance HIV infection and replication. Research has shown that activation of the mu-opioid receptor (MOR) elevates the expression of the HIV-1 entry co-receptor CXCR4 on T-lymphocytes in the peripheral nervous system, thus allowing for enhanced viral entry and invasion. Although the exact mechanism for opioid modulation of CXCR4 expression and subsequent exacerbation of HIV is unknown, several hypotheses exist. One hypothesis is that MOR and CXCR4 are functionally interacting through the formation of a heterodimer. This …

National And Local Antibiotic Prescribing Trends And Prescribing Appropriateness In Older Adults, Fawaz M. Alotaibi

Theses and Dissertations

Background: Antibiotic overuse/misuse has been documented in several reports to increase the risk of Clostridioides difficile (C.diff) infection and antibiotic resistance. The older adult population is more prone to use antibiotic medications than any other age group due to decreased immune function, use of urinary catheters, ventilation during hospitalization and other factors. Antibiotic resistance and C.diff are major public health problems. However, studies examining the trends of antibiotic use and the association between the antibiotic use and negative health outcomes among older adults in the outpatient and emergency department settings are limited.

Objectives: The main objectives of this …

Towards The Rational Design And Application Of Polymers For Gene Therapy: Internalization And Intracellular Fate, Landon Alexander Mott

Theses and Dissertations--Chemical and Materials Engineering

Gene therapy is an approach for the treatment of acquired cancers, infectious disease, degenerative disease, and inherited genetic indications. Developments in the fields of immunotherapies and CRISPR/Cas9 genome editing are revitalizing the efforts to move gene therapy to the forefront of modern medicine. However, slow progress and poor clinical outcomes have plagued the field due to regulatory and safety concerns associated with the flagship delivery vector, the recombinant virus. Immunogenicity and poor transduction in certain cell types severely limits the utility of viruses as a delivery agent of nucleic acids. As a result, significant efforts are being made to develop …

State And Regional Comparisons Of Breastfeeding Policies And Rates: A National Study, Erin Johnson

Honors Theses

State legislation focused on promoting and supporting breastfeeding is relatively new, beginning in the 1990s. The purpose of this study is to determine if there is an association between state breastfeeding rates and state breastfeeding legislation and other institutional policies. The Centers for Disease Control and Prevention releases breastfeeding report cards with the most up-to-date state breastfeeding rates. These reports are used to examine the relationship between state breastfeeding rates and number of breastfeeding policies passed by a state. Government initiatives, such as Healthy People Initiative, and organizational practices, such as Baby-Friendly USA Inc., are also studied to determine their …

Development Of Ligand-Kinase Binding Affinity Predictive Model, Govinda Kc

Open Access Theses & Dissertations

Prediction of interaction between drugs or drug like compounds and targets, is of high importance in drug discovery process as it provides important insights into therapeutic potential and possible adverse effects. As the experimental testing would be highly expensive, laborious and time consuming, screening the molecules computationally before performing experiments would be cost effective, faster and convenient as a method of approach. In this study, I have developed computational models, leveraging machine learning techniques, to predict drug-kinase binding affinities. The predictive model is mainly built using the Random Forest (RF) machine learning method. This study is focused on kinases because …

Assessing Appropriateness Of Inpatient Rifaximin Use In A Community Health System, Alissa Keillor Pharmd, Sarah Pfaehler Pharmd, Mba, Bcps, Lorin Yolch Pharmd, Bcgp, Bcac

Parkview Pharmacy Department

2019 ASHP Midyear Clinical Meeting / Las Vegas, Nevada / Poster # 11-135

Objective: To evaluate the appropriateness of inpatient rifaximin use and healthcare resource utilization best-practices within a community health-system.

Precision Medicine Reimbursement Policy Landscape, Nisita Jirawutkornkul

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: Access to precision medicine is limited due to many factors such as precision medicine technology of each country, high-cost technology that requires high finance, limitations on knowledge and competency of personnel and access to precision medicine. Each country manages access to precision medicine differently. The existing evidences of precision medicine reimbursement policy were limited. Objective: To explore reimbursement decision of precision medicine focusing on diagnostic tests and factors associated with reimbursement decision among high-income and upper-middle-income countries. Methods: A targeted review of literatures was conducted through PubMed, MEDLINE, Embase, Cochrane Library, and hand-searching. The study included 13 selected precision …