Efficacy of Cefiderocol Against Endophthalmitis Isolates.

Endophthalmitis is an intraocular microbial infection that can lead to permanent blindness, even with prompt anti-microbial therapy. Multi-drug-resistant organisms are on the rise, potentially limiting the efficacy of current empiric antibiotic therapies of intravitreal ceftazidime and vancomycin. Cefiderocol is a recent FDA- and EMA-approved antibiotic for multi-drug-resistant Gram-negative bacteria.

The Efficacy of Topical Cefiderocol Treatment of Experimental Extensively Drug-Resistant Keratitis Is Dependent upon the State of the Corneal Epithelium.

An overlooked factor in the efficacy of topical antibiotics to treat bacterial keratitis is the state of the corneal epithelium. Recently, we evaluated topical cefiderocol for the treatment of extensively drug-resistant (XDR) (PA) keratitis in eyes with the corneal epithelium abraded. The goal of this study was to use the same model with the corneal epithelium left intact to evaluate the efficacy of cefiderocol and other antibiotics and compare the results to those of the previous study.

The Generation of an ocular anti-inflammatory biotherapeutic to enhance wound healing.

Microbes exist at and colonize mucosal surfaces striking a balance with the host immune system, so that these microbes can thrive on host tissues without causing pathology. Because of this, mucosal barrier-colonizing bacteria can be leveraged to act as long-term delivery vehicles for naturally derived therapeutics. Here, we use a mouse model of corneal wound healing to show that the eye-colonizing bacterium, Corynebacterium mastitidis (C.

Cefiderocol Is an Effective Topical Monotherapy for Experimental Extensively Drug-Resistant Keratitis.

Purpose: To test cefiderocol, a siderophore-cephalosporin antibiotic for topical monotherapy treatment of experimental extensively drug-resistant (XDR) keratitis.

Design: Preclinical study.

Subjects And Controls: Deidentified keratitis isolates, XDR from eye drop outbreak, rabbits, saline, cefiderocol 50 mg/ml, ciprofloxacin 0.

Identification of an N-terminal tag (580N) that improves the biosynthesis of fluorescent proteins in Francisella tularensis and other Gram-negative bacteria.

Utilization of fluorescent proteins is widespread for the study of microbial pathogenesis and host-pathogen interactions. Here, we discovered that linkage of the 36 N-terminal amino acids of FTL_0580 (a hypothetical protein of Francisella tularensis) to fluorescent proteins increases the fluorescence emission of bacteria that express these recombinant fusions. This N-terminal peptide will be referred to as 580N.

Predatory bacteria prevent the proliferation of intraocular and fluoroquinolone-resistant .

Endogenous endophthalmitis caused by Gram-negative bacteria is an intra-ocular infection that can rapidly progress to irreversible loss of vision. While most endophthalmitis isolates are susceptible to antibiotic therapy, the emergence of resistant bacteria necessitates alternative approaches to combat intraocular bacterial proliferation. In this study the ability of predatory bacteria to limit intraocular growth of , , and was evaluated in a New Zealand white rabbit endophthalmitis prevention model.

Genome sequence generated by hybrid Nanopore-Illumina assembly of an extensively drug-resistant strain from a keratitis outbreak.

Here, we report the genome sequence of an extensively drug-resistant associated with a keratitis outbreak. This isolate was from the Center for Disease Control and Prevention and originates from a cornea. This sequence will facilitate studies of extensively drug resistant bacteria.

A rise in the frequency of mutant among keratitis isolates between 1993 and 2021.

Introduction: causes vision threatening keratitis. The transcription factor regulates virulence factors in response to the quorum sensing molecule N-3-oxo-dodecanoyl-L-homoserine lactone. isolates with mutations are characterized by an iridescent high sheen phenotype caused by a build-up of 2-heptyl-4-quinolone.

Intra-ocular Predation of Fluoroquinolone-Resistant and by Predatory Bacteria.

Endogenous endophthalmitis caused by Gram-negative bacteria is an intra-ocular infection that can rapidly progress to irreversible loss of vision. While most endophthalmitis isolates are susceptible to antibiotic therapy, the emergence of resistant bacteria necessitates alternative approaches to combat intraocular bacterial proliferation. In this study the ability of predatory bacteria to limit intraocular growth of , , and was evaluated in a New Zealand White rabbit endophthalmitis prevention model.

Cefiderocol is an effective topical monotherapy for experimental extensively-drug resistant keratitis.

Purpose: To test cefiderocol, a siderophore-cephalosporin antibiotic for topical monotherapy treatment of experimental extensively drug resistant (XDR) keratitis.

Design: Preclinical study.

Subjects And Controls: Deidentified keratitis isolates, XDR from eye drop outbreak, rabbits, saline, cefiderocol 50 mg/ml, ciprofloxacin 0.

Rise in frequency of mutant among keratitis isolates between 1993 and 2021.

causes severe vision threatening keratitis. LasR is a transcription factor that regulates virulence associated genes in response to the quorum sensing molecule N-3-oxo-dodecanoyl-L-homoserine lactone. isolates with mutations are characterized by an iridescent high sheen phenotype caused by a build-up of 2-heptyl-4-quinolone.

Predatory bacteria can reduce Pseudomonas aeruginosa induced corneal perforation and proliferation in a rabbit keratitis model.

Purpose: Pseudomonas aeruginosa keratitis is a severe ocular infection that can lead to perforation of the cornea. In this study we evaluated the role of bacterial quorum sensing in generating corneal perforation and bacterial proliferation and tested whether co-injection of the predatory bacteria Bdellovibrio bacteriovorus could alter the clinical outcome. P.

Extending the use of biologics to mucous membranes by attachment of a binding domain.

Biologics are almost exclusively administered systemically, but localized delivery is preferable as it minimizes off-target exposure and allows more aggressive treatments. Topical application of biologics to epithelia is generally ineffective because most are covered with fluids and biologics are washed out too quickly to have significant therapeutic effects. Here we explore the idea that attaching a binding domain can serve as an "anchor" to extend the residency time of biologics on wet epithelia, allowing their effective use even with infrequent applications.

Predatory Bacteria can Reduce Induced Corneal Perforation and Proliferation in a Rabbit Keratitis Model.

Purpose: keratitis is a severe ocular infection that can lead to perforation of the cornea. In this study we evaluated the role of bacterial quorum sensing in generating corneal perforation and bacterial proliferation and tested whether co-injection of the predatory bacteria could alter the clinical outcome. with mutations were observed among keratitis isolates from a study collecting samples from India, so an isogenic mutant strain of was included.

Genetic Manipulation of Corynebacterium mastitidis to Better Understand the Ocular Microbiome.

Purpose: Corynebacterium spp. are Gram-positive bacteria commonly associated with the ocular surface. Corynebacterium mastitidis was isolated from mouse eyes and was demonstrated to induce a beneficial immune response that can protect the eye from pathogenic infection.

The Short-chain Fatty Acid Propionic Acid Activates the Rcs Stress Response System Partially through Inhibition of d-Alanine Racemase.

The Enterobacterial Rcs stress response system reacts to envelope stresses through a complex two-component phosphorelay system to regulate a variety of environmental response genes, such as capsular polysaccharide and flagella biosynthesis genes. However, beyond Escherichia coli, the stresses that activate Rcs are not well-understood. In this study, we used a Rcs system-dependent luminescent transcriptional reporter to screen a library of over 240 antimicrobial compounds for those that activated the Rcs system in Serratia marcescens, a family bacterium.

IgaA Protein, GumB, Has a Global Impact on the Transcriptome and Surface Proteome of Serratia marcescens.

Bacterial stress response signaling systems, like the Rcs system are triggered by membrane and cell wall damaging compounds, including antibiotics and immune system factors. These regulatory systems help bacteria survive envelope stress by altering the transcriptome resulting in protective phenotypic changes that may also influence the virulence of the bacterium. This study investigated the role of the Rcs stress response system using a clinical keratitis isolate of Serratia marcescens with a mutation in the gene.

Reactive silver inks for antiviral, repellent medical textiles with ultrasonic bleach washing durability compared to silver nanoparticles.

Medical textiles are subject to particularly harsh disinfection procedures in healthcare settings where exposure risks are high. This work demonstrates a fabric treatment consisting of a reactive silver ink and low surface energy PDMS polymer that provides for superhydrophobicity and antiviral properties against enveloped herpes simplex virus stocks even after extended ultrasonic bleach washing. The antiviral properties of reactive silver ink has not been previously reported or compared with silver nanoparticles.

The in vitro Evaluation of the Activity of COVID-19 Antiviral Drugs Against Adenovirus.

Purpose: Presently, there is no approved antiviral therapy for adenovirus (HAdV) ocular infections. During the COVID-19 pandemic, increased attention has been focused on antiviral treatments. Remdesivir, hydroxychloroquine, ivermectin, and umifenovir (Arbidol) have been touted as potential antiviral treatments for COVID-19.

Bacterial Keratitis: imilar Bacterial and Clinical Outcomes in Female versus Male New Zealand White Rabbits Infected with .

Purpose: Females and males respond differently to a number of systemic viral infections. Differences between females and males with respect to the severity of keratitis caused by Gram-negative bacteria such as are less well established.

Methods: In this study, we injected female and male New Zealand White rabbit corneas with a keratitis isolate of and evaluated the eyes after 48 hours for a number of clinical and microbiological parameters.

Antibiotics Used in Empiric Treatment of Ocular Infections Trigger the Bacterial Rcs Stress Response System Independent of Antibiotic Susceptibility.

The Rcs phosphorelay is a bacterial stress response system that responds to envelope stresses and in turn controls several virulence-associated pathways, including capsule, flagella, and toxin biosynthesis, of numerous bacterial species. The Rcs system also affects antibiotic tolerance, biofilm formation, and horizontal gene transfer. The Rcs system of the ocular bacterial pathogen was recently demonstrated to influence ocular pathogenesis in a rabbit model of keratitis, with Rcs-defective mutants causing greater pathology and Rcs-activated strains demonstrating reduced inflammation.

Clearance of Gram-Negative Bacterial Pathogens from the Ocular Surface by Predatory Bacteria.

It was previously demonstrated that predatory bacteria are able to efficiently eliminate Gram-negative pathogens including antibiotic-resistant and biofilm-associated bacteria. In this proof-of-concept study we evaluated whether two species of predatory bacteria, and , were able to alter the survival of Gram-negative pathogens on the ocular surface. Clinical keratitis isolates of (strain PAC) and (strain K904) were applied to the ocular surface of NZW rabbits followed by application of predatory bacteria.