Bacterial Infections and Mycoses Commons^™

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 …

Chloroquine-Susceptible And -Resistant Plasmodium Falciparum Strains Survive High Chloroquine Concentrations By Becoming Dormant But Are Eliminated By Prolonged Exposure, Johan Ursing, Rasmus Johns, Berit Aydin-Schmidt, Carla Calçada, Poul-Erik Kofoed, Najia Karim Ghanchi, Maria Isabel Veiga, Lars Rombo

Department of Pathology and Laboratory Medicine

Background: Plasmodium falciparum strains that are resistant to standard-dose chloroquine can be treated by higher chloroquine concentrations maintained for a longer time in vivo.
Objectives: To determine the relative importance of chloroquine concentrations versus exposure time for elimination of chloroquine-susceptible and -resistant P. falciparum in vitro.
Methods: Chloroquine-susceptible (3D7) and -resistant (FCR3) strains were exposed in vitro to 1, 2, 4, 8, 16 or 32 times their respective 90% inhibitory chloroquine concentrations for 3, 5, 7 or 14 days and then followed until recrudescence, or not, by 42 days after the end of exposure.
Results: Exposure to chloroquine appeared to …

The Large And Small Of It: The Microbiome And Metagenomics, Austin Hopkins, Elaina Gollmar, Jessica Fernandez, Shawn Wolf, Austin Hilverding, Andrew M. Roecker

Pharmacy and Wellness Review

Metagenomics, the analysis of the microbial genome, permits scientists to understand the influences of external sources including diet, metabolism and antibiotics on the human microbiome. Research has revealed the possibility of a core symbiosis between humans and bacteria. The main role of the human microbiome is to aid in digestion, but identified ancillary roles include immunologic homeostasis and infection prevention. Quantifying the composition and variability of the microbiome will help lead to future treatments or preventive strategies against unhealthy change. A variety of methods may be used to define the microbiome, and 16S amplicon sequencing is primarily utilized today. Probiotics …

Variants Associated With Bedaquiline (Bdq) Resistance Identified In Rv0678 And Efflux Pump Genes In Mycobacterium Tuberculosis Isolates From Bdq Naïve Tb Patients In Pakistan, Dania Khalid Saeed, Sadia Shakoor, Safina Abdul Razzak, Zahra Hasan, Saba Faraz Sabzwari, Zahida Azizullah, Akber Kanji, Asghar Nasir, Samreen Shafiq, Najia Karim Ghanchi, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background: Mutations in the Rv0678, pepQ and atpE genes of Mycobacterium tuberculosis (MTB) have been reported to be associated with reduced antimycobacterial susceptibility to bedaquiline (BDQ). Resistance conferring mutations in treatment naïve MTB strains is likely to have implications for BDQ based new drug regimen that aim to shorten treatment duration. We therefore investigated the genetic basis of resistance to BDQ in MTB clinical isolates from BDQ naïve TB patients from Pakistan. In addition, mutations in genes associated with efflux pumps were investigated as an alternate mechanism of resistance.
Methods: Based on convenience sampling, we studied 48 MTB clinical isolates …

Evaluation Of Step-Down Oral Antibiotic Therapy For Uncomplicated Streptococcal Bloodstream Infections On Clinical Outcomes, Amy Y. Kang, Richard Beuttler, Emi Minejima

Pharmacy Faculty Articles and Research

Background: Despite the severity and frequency of streptococcal bloodstream infections (BSIs), the effectiveness of oral definitive therapy remains unknown. The objective of this study was to evaluate the clinical outcomes of step-down oral antibiotics for the treatment of uncomplicated streptococcal BSIs.

Methods: In this retrospective cohort study, adult patients admitted with uncomplicated streptococcal BSI between June 2015 and June 2017 were included. Patients were excluded if they received <48 h of antibiotic therapy; therapy was started >48 h after first positive culture; had complicated infections of endocarditis, bone and joint infections, or central nervous system infections; Pitt bacteremia score (PBS) ⩾ 4; or failed to respond …

Optimizing Empiric Vancomycin Use In Febrile Neutropenia Patients, Nicole Tadros, Erika Dittmar, Radhan B. Gopalani

Nursing & Health Sciences Research Journal

Introduction: National guidelines do not support routine empiric vancomycin use in the initial management of febrile neutropenia (FN) and only recommend it in patients with specific clinical indications. This bi-phasic quality improvement project aimed to evaluate current vancomycin use in FN and improve compliance with a guideline-driven algorithm (GDA) to ensure appropriate prescribing and therapy duration in a community hospital.

Methods: Phase I was a retrospective review of charts of adults receiving empiric vancomycin therapy for FN at a community hospital. Phase II was a prospective review of charts of patients with FN, who received pharmacist-led interventions, to improve de-escalation …

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 …

Lipoxin A 4 (Lxa 4 ) Promotes Reduction And Antibiotic Efficacy Against Pseudomonas Aeruginosa Biofilm, Julianne M. Thornton, Jean Walker, Prem Yugandhar Kadiyam Sundarasivarao, Bernd Spur, Ana Rodriguez, Kingsley Yin

Rowan-Virtua Research Day

Pseudomonas aeruginosa (P aeruginosa) is an opportunistic bacterium commonly found in wound infections and airways of cystic fibrosis patients P aeruginosa readily forms biofilms which can reduce the efficacy of antibiotics used to eradicate the pathogen We have previously shown that a Specialized Pro resolving Mediator ( Lipoxin A 4 (LxA 4 is a quorum sensing inhibitor which can reduce P aeruginosa virulence In this study, we examined the direct actions of LxA 4 and RvD 2 on P aeruginosa biofilm formation and virulence gene expression The influence of LxA 4 on antibiotic efficacy and the combined effects on biofilm …

Stability Evaluation Of Extemporaneously Compounded Vancomycin Ophthalmic Drops: Effect Of Solvents And Storage Conditions, Christopher Ross, Basir Syed, Joanna Pak, Vishal Jhanji, Jason Yamaki, Ajay Sharma

Pharmacy Faculty Articles and Research

Vancomycin is the drug of choice for methicillin-resistant Staphylococcus aureus keratitis and other ocular infections. Vancomycin ophthalmic drops are not commercially available and require compounding. The present study was designed to investigate the stability of vancomycin ophthalmic drops in normal saline, phosphate-buffered saline (PBS), and balanced salt solution (BSS) while stored at room temperature or under refrigeration. Vancomycin ophthalmic drops (50 mg/mL) were aseptically prepared from commercially available intravenous powder using PBS, BSS, and saline. Solutions were stored at room temperature and in a refrigerator for 28 days. The vancomycin stability was tested by a microbiology assay and high-performance liquid …

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 …

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.

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 …

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) …

Impact Of Required Antibiotic Stop Dates And Indications On Length Of Treatment In Hospitalized Patients With Pneumonia, Amanda Haddad, Kathryn Hernando, Kayihura Manigaba, Abigail Antigua

Infectious Disease

Purpose: The CDC Core Elements of Hospital Antibiotic Stewardship Programs recommends implementing policies to support optimal antibiotic prescribing including documentation of dose, duration and indication. On January 31, 2017, the study institution implemented new physician order entry screens in the electronic health record requiring the input of indication and duration on all antibiotic orders. The objective of this study is to determine if implementation of mandatory indication and duration for antibiotic orders decreases antibiotic duration of therapy in hospitalized patients with pneumonia.

Methods: This study was submitted to the Institutional Review Committee for approval. The clinical pharmacy surveillance platform, …

Sterile Compounding: Regulations Addressed After The Meningitis Outbreak Of 2012, Kelly M. Dye, Tara M. Tokar, Halle M. Orlinski, Heather Helsel, Marcia M. Worley

Pharmacy and Wellness Review

No abstract provided.

Antimicrobial Stewardship Programs, Kevin Stack, Eric Stack, Stelios Theophanous, Anne Gentry, Jason M. Pogue

Pharmacy and Wellness Review

Antimicrobial Stewardship Programs (ASPs) are becoming increasingly prevalent in the United States as concerns continue to mount regarding antimicrobial resistance and the lack of new, novel antibiotics being introduced. There are a multitude of factors that have contributed to the escalation in antimicrobial resistance, with some of the more common concerns being overly broad antimicrobial coverage and prolonged antimicrobial treatment amongst others. While antimicrobial resistance is a problem of international proportion, each health care institution remains responsible for assessing its own protocols pertinent to antimicrobial usage. ASPs have had unparalleled success in achieving their goals due to the collaboration of …

Legionnaires' Disease, A Rising Occurrence In The United States, Jennifer Harklerode, Olivia Henton, Myranda Smith, Rebecca Worden, Andrew Roecker

Pharmacy and Wellness Review

Legionella pneumophila, a microscopic bacterium usually responsible for a number of illnesses and fatalities, can eliminate a local population, a region or even a nation. In 1976, L. pneumophila was first discovered due to a number of cases presenting with pneumonia-like symptoms. These cases occurred in an isolated population attending an American Legion convention in Philadelphia, Pennsylvania, therefore lending to the name Legionella. Usually found in aquatic environments such as lakes, streams, cooling towers, air conditioning systems and hot tubs, its ability to thrive in artificial and natural environments makes it an ideal bacterium. L. pneumophila can be transmitted via …

Combating Antibiotic Resistance In The 21st Century, Kevin Krivanek, Brian Heilbronner, Brendan Rasor, Kelsey Lindsley, Andrew Roecker

Pharmacy and Wellness Review

Antibiotic resistance is one of the most significant challenges facing the medical community today. In response, the Centers for Disease Control and Prevention (CDC) created a list of the greatest antibiotic resistance threats, a number of which are gram-positive bacteria. The cell wall of these organisms has long been a favored target of antibiotic therapies, but the development of numerous resistance mechanisms has led to widespread resistance against nearly all major antibiotic compounds on the market. The medical community is faced with the task of developing better antibiotic compounds that preclude the spread of bacterial resistance and also increasing the …

Whooping Cough: A Pharmacist's Role In An Emerging Endemic, Haley Armstrong, Lydia Suchecki, Sarah Lipperman, Taylor Roberson, Andrew M. Roecker

Pharmacy and Wellness Review

Pertussis is an acute infectious disease caused by the organism Bordetella pertussis and characterized by a "whooping cough." Incidence of the disease had declined since the development of a vaccine, but is now increasing in reported cases. This increase has been attributed to both an increased awareness but also surmised to be related to a decrease in vaccinations. The pertussis vaccine is given in conjunction with tetanus and diphtheria vaccines to children before the age of 6 in five separate injections over the course of four to six years. A booster is now recommended for the older child and adults …

Fda Approves New Tuberculosis Drug: Bedaquiline (Sirturo®), Megan Ruffner, Kent Wilin, Charles Hay, Zachary Crawford, Andrew Roecker

Pharmacy and Wellness Review

Tuberculosis (TB), caused by the acid-fast bacilli (AFB) Mycobacterium tuberculosis, is an infectious disease that continues to greatly impact morbidity and mortality worldwide; in 2011 it caused 1.4 million deaths. Some strains of the bacteria have become resistant to current treatment regimens, resulting in multidrug-resistant (MOR) and extensively drugresistant (XOR) TB. The emergence of these resistant strains of bacteria calls for new treatment regimens that can quickly and effectively eradicate the organism. The U.S. Food and Drug Administration (FDA) recently approved Sirturo® (bedaquiline) with the indication of MDR pulmonary TB. Bedaquiline introduces a novel mechanism of action via the inhibition …

Fidaxomicin (Dificid®): New Antibiotic Approved For The Treatment Of Clostridium Difficile Infections, Sara M. Mcallister, Zachary Crawford, Joshua Ilenin, Ellen Hazelet, Andrew M. Roecker

Pharmacy and Wellness Review

Clostridium difficile is a gram-positive, spore forming bacteria normally transmitted by the fecal-oral route. Infection develops in patients with decreased normal gut flora and is typically associated with recent antibiotic use. Other risk factors include bowel surgery, compromised immune system function, extended hospital stays, and other underlying diseases. C. difficile bacteria produce two toxins, which cause increased intestinal fluid secretion and inflammation. Patients commonly present with diarrhea, abdominal discomfort, loss of appetite, and nausea. Current treatment guidelines are to discontinue antimicrobial agents and increase hydration. Less severe C. difficile associated diarrhea (CDAD) cases are treated with metronidazole 500 mg three …

The Impact Of Concomitant Empiric Cefepime On Patient Outcomes Of Methicillin-Resistant Staphylococcus Aureus Bloodstream Infections Treated With Vancomycin, Evan J. Zasowski, Trang D. Trinh, Safana M. Atwan, Marina Merzlyakova, Abdalhamid M. Langf, Sahil Bhatia, Michael J. Rybak

Faculty Publications & Research of the TUC College of Pharmacy

Background: Data suggest that vancomycin + β-lactam combinations improve clearance of methicillin-resistant Staphylococcus aureus(MRSA) bloodstream infections (BSIs). However, it is unclear which specific β-lactams confer benefit. This analysis evaluates the impact of concomitant empiric cefepime on outcomes of MRSA BSIs treated with vancomycin.

Methods: Retrospective cohort study of adults with MRSA BSI from 2006 to 2017. Vancomycin + cefepime therapy was defined as ≥24 hours of cefepime during the first 72 hours of vancomycin. The primary outcome was microbiologic failure, defined as BSI duration ≥7 days and/or 60-day recurrence. Multivariable logistic regression was used to evaluate the association between …

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.

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 …

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 - …

Loop-Mediated Isothermal Amplification Methods For Diagnosis Of Bacterial Meningitis, Mitsuko Seki, Paul E. Kilgore, Eun Jin Kim, Makoto Ohnishi, Satoshi Hayakawa, Dong Wook Kim

Department of Pharmacy Practice

The rapid, accurate, and efficient identification of an infectious disease is critical to ensure timely clinical treatment and prevention in public health settings. In 2015, meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis was responsible for 379,200 (range: 322,700–444,700) deaths. Clinical features alone cannot determine whether bacterial meningitis is present; an analysis of cerebrospinal fluid (CSF) is essential. Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification method offering an alternative to polymerase chain reaction (PCR). LAMP-based assays for detection of three leading bacteria in CSF for diagnosis of meningitis have been established. The typing assays …

Discovery Of New Antimicrobial Options And Evaluation Of Aminoglycoside Resistance Enzyme-Associated Resistance Epidemic, Selina Y. L. Holbrook

Theses and Dissertations--Pharmacy

The extensive and sometimes incorrect and noncompliant use of various types of antimicrobial agents has accelerated the development of antimicrobial resistance (AMR). In fact, AMR has become one of the greatest global threat to human health in this era. The broad-spectrum antibiotics aminoglycosides (AGs) display excellent potency against most Gram-negative bacteria, mycobacteria, and some Gram-positive bacteria, such as Staphylococcus aureus. The AG antibiotics amikacin, gentamicin, kanamycin, and tobramycin are still commonly prescribed in the U.S.A. for the treatment of serious infections. Unfortunately, bacteria evolve to acquire resistance to AGs via four different mechanisms: i) changing in membrane permeability to …

Calcium Phosphate As A Key Material For Socially Responsible Tissue Engineering, Vuk Uskoković, Victoria M. Wu

Pharmacy Faculty Articles and Research

Socially responsible technologies are designed while taking into consideration the socioeconomic, geopolitical and environmental limitations of regions in which they will be implemented. In the medical context, this involves making therapeutic platforms more accessible and affordable to patients in poor regions of the world wherein a given disease is endemic. This often necessitates going against the reigning trend of making therapeutic nanoparticles ever more structurally complex and expensive. However, studies aimed at simplifying materials and formulations while maintaining the functionality and therapeutic response of their more complex counterparts seldom provoke a significant interest in the scientific community. In this review …