Bacterial Infections and Mycoses Commons^™

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 …

Epithelial Cell Lysates Induce Exos Expression And Secretion By Pseudomonas Aeruginosa, Victoria Hritonenko, Matteo Metruccio, David J. Evans, Suzanne Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

No abstract provided.

The Impact Of Exos On Pseudomonas Aeruginosa Internalization By Epithelial Cells Is Independent Of Fleq And Correlates With Bistability Of Type Three Secretion System Gene Expression, Abby R. Kroken, Camille K. Chen, David J. Evans, Timothy L. Yahr, Suzanne M. J. Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

Pseudomonas aeruginosa is internalized into multiple types of epithelial cell in vitro and in vivo and yet is often regarded as an exclusively extracellular pathogen. Paradoxically, ExoS, a type three secretion system (T3SS) effector, has antiphagocytic activities but is required for intracellular survival of P. aeruginosaand its occupation of bleb niches in epithelial cells. Here, we addressed mechanisms for this dichotomy using invasive (ExoS-expressing) P. aeruginosaand corresponding effector-null isogenic T3SS mutants, effector-null mutants of cytotoxic P. aeruginosa with and without ExoS transformation, antibiotic exclusion assays, and imaging using a T3SS-GFP reporter. Except for effector-null PA103, all strains were internalized while …

Mucosal Fluid Glycoprotein Dmbt1 Suppresses Twitching Motility And Virulence Of The Opportunistic Pathogen Pseudomonas Aeruginosa, Jianfang Li, Matteo E. O. Metruccio, David J. Evans, Suzanne M. J. Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

It is generally thought that mucosal fluids protect underlying epithelial surfaces against opportunistic infection via their antimicrobial activity. However, our published data show that human tear fluid can protect against the major opportunistic pathogen Pseudomonas aeruginosa independently of bacteriostatic activity. Here, we explored the mechanisms for tear protection, focusing on impacts of tear fluid on bacterial virulence factor expression. Results showed that tear fluid suppressed twitching motility, a type of surface-associated movement conferred by pili. Previously, we showed that twitching is critical for P. aeruginosa traversal of corneal epithelia, exit from epithelial cells after internalization, and corneal virulence. Inhibition …

Human Tear Fluid Reduces Culturability Of Contact Lens-Associated Pseudomonas Aeruginosa Biofilms But Induces Expression Of The Virulence-Associated Type Iii Secretion System, Yvonne T. Wu, Connie Tam, Lucia S. Zhu, David J. Evans, Suzanne M. J. Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

Purpose

The type III secretion system (T3SS) is a significant virulence determinant for Pseudomonas aeruginosa. Using a rodent model, we found that contact lens(CL)-related corneal infections were associated with lens surface biofilms. Here, we studied the impact of human tear fluid on CL-associated biofilm growth and T3SS expression.

Methods

P. aeruginosa biofilms were formed on contact lenses for up to 7 days with or without human tear fluid, then exposed to tear fluid for 5 or 24 h. Biofilms were imaged using confocal microscopy. Bacterial culturability was quantified by viable counts, and T3SS gene expression measured …

Pseudomonas Aeruginosa Outer Membrane Vesicles Triggered By Human Mucosal Fluid And Lysozyme Can Prime Host Tissue Surfaces For Bacterial Adhesion, Matteo M. E. Metruccio, David J. Evans, Manal M. Gabriel, Jagath L. Kadurugamuwa, Suzanne M. J. Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

Pseudomonas aeruginosa is a leading cause of human morbidity and mortality that often targets epithelial surfaces. Host immunocompromise, or the presence of indwelling medical devices, including contact lenses, can predispose to infection. While medical devices are known to accumulate bacterial biofilms, it is not well understood why resistant epithelial surfaces become susceptible to P. aeruginosa. Many bacteria, including P. aeruginosa, release outer membrane vesicles (OMVs) in response to stress that can fuse with host cells to alter their function. Here, we tested the hypothesis that mucosal fluid can trigger OMV release to compromise an epithelial barrier. This was tested using …

Isavuconazole In The Treatment Of Invasive Aspergillosis And Mucormycosis Infections, Monica A. Donnelley, Elizabeth S. Zhu, George R. Thompson Iii

Faculty Publications & Research of the TUC College of Pharmacy

We have a limited arsenal with which to treat invasive fungal infections caused by Aspergillus and Mucorales. The morbidity and mortality for both pathogens remains high. A triazole antifungal, isavuconazole, was recently granted approval by the US Food and Drug Administration and the European Medicines Agency for the treatment of invasive aspergillosis and mucormycosis. A randomized double-blind comparison trial for the treatment of invasive aspergillosis found isavuconazole noninferior to voriconazole. A separate, open-label study evaluating the efficacy of isavuconazole in the treatment of mucormycosis found comparable response rates to amphotericin B and posaconazole treated historical controls. The prodrug isavuconazonium sulfate …

Development Of A Multivalent Subunit Vaccine Against Tularemia Using Tobacco Mosaic Virus (Tmv) Based Delivery System, Sukalyani Banik, Ahd Ahmed Mansour, Ragavan Varadharajan Suresh, Sherri Wykoff-Clary, Meenakshi Malik, Alison A. Mccormick, Chandra Shekhar Bakshi

Faculty Publications & Research of the TUC College of Pharmacy

Francisella tularensisis a facultative intracellular pathogen, and is the causative agent of a fatal human disease known as tularemia. F. tularensis is classified as a Category A Biothreat agent by the CDC based on its use in bioweapon programs by several countries in the past and its potential to be used as an agent of bioterrorism. No licensed vaccine is currently available for prevention of tularemia. In this study, we used a novel approach for development of a multivalent subunit vaccine against tularemia by using an efficient tobacco mosaic virus (TMV) based delivery platform. The multivalent subunit vaccine was formulated …

Pseudomonas Aeruginosa-Induced Bleb-Niche Formation In Epithelial Cells Is Independent Of Actinomyosin Contraction And Enhanced By Loss Of Cystic Fibrosis Transmembrane-Conductance Regulator Osmoregulatory Function, Amber L. Jolly, Desire Takawira, Olufolarin O. Oke, Sarah A. Whiteside, Stephanie W. Chang, Emily R. Wen, David J. Evans

Faculty Publications & Research of the TUC College of Pharmacy

The opportunistic pathogen Pseudomonas aeruginosa can infect almost any site in the body but most often targets epithelial cell-lined tissues such as the airways, skin, and the cornea of the eye. A common predisposing factor is cystic fibrosis (CF), caused by defects in the cystic fibrosis transmembrane-conductance regulator (CFTR). Previously, we showed that when P. aeruginosa enters epithelial cells it replicates intracellularly and occupies plasma membrane blebs. This phenotype is dependent on the type 3 secretion system (T3SS) effector ExoS, shown by others to induce host cell apoptosis. Here, we examined mechanisms for P. aeruginosa-induced bleb formation, focusing on its …

Cytotoxic Clinical Isolates Of Pseudomonas Aeruginosa Identified During The Steroids For Corneal Ulcers Trial Show Elevated Resistance To Fluoroquinolones, Durga S. Borkar, Nisha R. Acharya, Chelsia Leong, Prajna Lalitha, Muthiah Srinivasan, Catherine E. Oldenburg, David J. Evans

Faculty Publications & Research of the TUC College of Pharmacy

Background: To determine the relationship between type three secretion genotype and fluoroquinolone resistance for P. aeruginosa strains isolated from microbial keratitis during the Steroids for Corneal Ulcers Trial (SCUT) and for two laboratory strains, PA103 and PAO1.

Methods: Confirmed P. aeruginosa isolates from the SCUT were divided into exoU(+) or exoU(−). The exoU(+) strains contained the gene encoding ExoU, a powerful phospholipase toxin delivered into host cells by the type three secretion system. Isolates were then assessed for susceptibility to fluoroquinolone, cephalosporin, and aminoglycoside antibiotics using disk diffusion assays. Etest was used to determine the MIC of moxifloxacin …