Efficacy of a Novel Antibiotic Drug Combination Toward Multidrug-Resistant Ocular Pathogens.

Purpose: Antimicrobial resistance is a global health threat, compounded by the reduction in the discovery of new antibiotics. A repurposed drugs-based approach could provide a viable alternative for the treatment of multidrug-resistant (MDR) bacterial infections. In this study, we sought to evaluate the in vitro efficacy of a novel drug combination, polymyxin B/trimethoprim (PT) + rifampin on MDR isolates from patients with bacterial keratitis in India.

and P infectious keratitis: key bacterial mechanisms that mediate pathogenesis and emerging therapeutics.

Bacterial keratitis (bacterial infection of the cornea) is a major cause of vision loss worldwide. Given the rapid and aggressive nature of the disease, immediate broad-spectrum antibiotics are essential to adequately treat this disease. However, rising antibiotic resistance continues to accelerate, rendering many commonly used therapeutics increasingly ineffective.

Case Report: Scleral hyperpigmentation associated with oral hydroxychloroquine use.

Hydroxychloroquine (HCQ) is a commonly used medication for its immunosuppressive and dermatologic effects. It has known ocular side effects, which include retinopathy, corneal deposits, and choroidal thinning. Herein, we report the first known case of HCQ-induced hyperpigmentation of the sclera.

Staphylococcal Enterotoxins Promote Virulence in Bacterial Keratitis.

Purpose: Staphylococcus aureus is an important cause of corneal infections (keratitis). To better understand the virulence mechanisms mediating keratitis, a recent comparative genomics study revealed that a set of secreted enterotoxins were found with higher prevalence among ocular versus non-ocular S. aureus clinical infection isolates, suggesting a key role for these toxins in keratitis.

Antimicrobial Drug-Drug Interactions in the Treatment of Infectious Keratitis.

Purpose: Infectious keratitis is a serious disease requiring immediate, intensive, and broad-spectrum empiric treatment to prevent vision loss. Given the diversity of organisms that can cause serious corneal disease, current guidelines recommend treatment with several antimicrobial agents simultaneously to provide adequate coverage while awaiting results of microbiology cultures. However, it is currently unknown how the use of multiple ophthalmic antimicrobial agents in combination may affect the efficacy of individual drugs.

Intrastromal Antibiotic Injection in Polymicrobial Keratitis: Case Report and Literature Review.

Bacterial keratitis (corneal infection) caused by more than one organism is rare and exceedingly difficult to treat due to variable antibiotic susceptibilities. Intrastromal injections of antibiotics may be necessary to achieve higher drug concentrations at the site of infection, particularly in the case of deep stromal disease refractory to topical therapy. However, while this approach is increasingly used for fungal keratitis, there is a paucity of the literature regarding the use of intrastromal antibiotics bacterial keratitis.

Antimicrobial Activity of a Triple Antibiotic Combination Toward Ocular Pseudomonas aeruginosa Clinical Isolates.

Purpose: Pseudomonas aeruginosa is a leading cause of corneal infections. Recently, we discovered an antimicrobial drug combination, polymyxin B/trimethoprim (PT) + rifampin, that displayed impressive efficacy toward P. aeruginosa in both in vitro and in vivo studies.

Retained polyvinyl chloride fragments in the cornea following trauma.

Purpose: PVC is a synthetic plastic polymer used worldwide for a wide range of applications. While it is often associated with ocular trauma, little is known regarding how PVC may interact with ocular tissues. Herein we report the clinical course of a patient with polyvinyl chloride (PVC) embedded in the cornea after a projectile injury, utilizing anterior segment optical tomography to study the relative antigenicity and reactivity of this industrial material in the cornea.

Genomics of Staphylococcus aureus ocular isolates.

Staphylococcus aureus is a major cause of ocular infections, often resulting in devastating vision loss. Despite the significant morbidity associated with these infections, little is yet known regarding the specific strain types that may have a predilection for ocular tissues nor the set of virulence factors that drive its pathogenicity in this specific biological niche. Whole genome sequencing (WGS) can provide valuable insight in this regard by providing a prospective, comprehensive assessment of the strain types and virulence factors driving disease among specific subsets of clinical isolates.

Efficacy of a Novel Ophthalmic Antimicrobial Drug Combination Toward a Large Panel of Staphylococcus aureus Clinical Ocular Isolates From Around the World.

Purpose: Staphylococcus aureus is a leading cause of keratitis requiring urgent antimicrobial treatment. However, rising antibiotic resistance has rendered current ophthalmic antibiotics increasingly ineffective. First, a diverse, ocular S.

Short-term, high-dose hydroxychloroquine corneal toxicity.

Purpose: To describe the corneal findings and management of a 61-year-old female with vortex keratopathy following short term, high dose hydroxychloroquine used in the setting of a clinical trial for recurrent breast cancer.

Observations: The patient was found to have significant corneal vortex keratopathy without retinal pathology within 3 months of 1200 mg daily hydroxychloroquine treatment as an adjuvant medication for cancer therapy. Cessation of the medication led to the resolution of the corneal verticillata within 1 month yet the vision did not return to baseline.

Anterior Segment Optical Coherence Tomography in Ocular Argyrosis.

Purpose: To highlight the novel application of anterior segment optical coherence tomography (AS-OCT) to detect corneal silver deposition in a case of ocular argyrosis.

Methods: This is a case report and review of the literature.

Results: A 67-year-old man with a 30-year history of chronic occupational exposure to silver-halides secondary to photographic film manufacturing presented with significant ocular argyrosis.

A Novel, Broad-Spectrum Antimicrobial Combination for the Treatment of Pseudomonas aeruginosa Corneal Infections.

Bacterial keratitis causes significant blindness, yet antimicrobial resistance has rendered current treatments ineffective. Polymyxin B-trimethoprim (PT) plus rifampin has potent activity against and , two important causes of keratitis. Here we further characterize this combination against in a murine keratitis model.

Development of a Broad-Spectrum Antimicrobial Combination for the Treatment of Staphylococcus aureus and Pseudomonas aeruginosa Corneal Infections.

and are two of the most common causes of bacterial keratitis and corresponding corneal blindness. Accordingly, such infections are predominantly treated with broad-spectrum fluoroquinolones, such as moxifloxacin. Yet, the rising fluoroquinolone resistance has necessitated the development of alternative therapeutic options.

Keratitis with Focal Descemet's Membrane Detachment and Intracorneal Hypopyon.

. To describe a unique case of keratitis associated with a rare manifestation of Descemet's membrane detachment and intracorneal hypopyon and to discuss challenges in diagnosis and management. .

Zinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment.

Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus are commonly associated with biofilm-associated wound infections that are recalcitrant to conventional antibiotics. As an initial means to identify agents that may have a greater propensity to improve clearance of wound-associated bacterial pathogens, we screened a Food and Drug Administration-approved drug library for members that display bactericidal activity toward 72-h-established P. aeruginosa biofilms using an adenylate kinase reporter assay for bacterial cell death.

Keratoprosthesis in Ectodermal Dysplasia.

Purpose: To describe the complex surgical management and novel medical approach for a keratoprosthesis (KPro Boston type I) in a monocular, 73-year-old patient with ectodermal dysplasia and chronic, noninfectious corneal necrosis.

Methods: Best-corrected visual acuity (BCVA) was measured with Snellen letters. Surgical intervention included an amniotic membrane graft, complete replacement of the KPro, conjunctival flap graft, corneal donor tissue grafts combined with inferior rectus muscle advancement, periosteal tissue graft, tarso-conjunctival flap construction, and symblepharolysis.

Clinically Relevant Growth Conditions Alter Acinetobacter baumannii Antibiotic Susceptibility and Promote Identification of Novel Antibacterial Agents.

Biological processes that govern bacterial proliferation and survival in the host-environment(s) are likely to be vastly different from those that are required for viability in nutrient-rich laboratory media. Consequently, growth-based antimicrobial screens performed in conditions modeling aspects of bacterial disease states have the potential to identify new classes of antimicrobials that would be missed by screens performed in conventional laboratory media. Accordingly, we performed screens of the Selleck library of 853 FDA approved drugs for agents that exhibit antimicrobial activity toward the Gram-negative bacterial pathogen Acinetobacter baumannii during growth in human serum, lung surfactant, and/or the organism in the biofilm state and compared those results to that of conventional laboratory medium.

Integrative and conjugative elements: mosaic mobile genetic elements enabling dynamic lateral gene flow.

Integrative and conjugative elements (ICEs) are a diverse group of mobile genetic elements found in both Gram-positive and Gram-negative bacteria. These elements primarily reside in a host chromosome but retain the ability to excise and to transfer by conjugation. Although ICEs use a range of mechanisms to promote their core functions of integration, excision, transfer and regulation, there are common features that unify the group.

Comparative ICE genomics: insights into the evolution of the SXT/R391 family of ICEs.

Integrating and conjugative elements (ICEs) are one of the three principal types of self-transmissible mobile genetic elements in bacteria. ICEs, like plasmids, transfer via conjugation; but unlike plasmids and similar to many phages, these elements integrate into and replicate along with the host chromosome. Members of the SXT/R391 family of ICEs have been isolated from several species of gram-negative bacteria, including Vibrio cholerae, the cause of cholera, where they have been important vectors for disseminating genes conferring resistance to antibiotics.

A toxin-antitoxin system promotes the maintenance of an integrative conjugative element.

SXT is an integrative and conjugative element (ICE) that confers resistance to multiple antibiotics upon many clinical isolates of Vibrio cholerae. In most cells, this approximately 100 Kb element is integrated into the host genome in a site-specific fashion; however, SXT can excise to form an extrachromosomal circle that is thought to be the substrate for conjugative transfer. Daughter cells lacking SXT can theoretically arise if cell division occurs prior to the element's reintegration.

Genomic and functional analysis of ICEPdaSpa1, a fish-pathogen-derived SXT-related integrating conjugative element that can mobilize a virulence plasmid.

Integrating conjugative elements (ICEs) are self-transmissible mobile elements that transfer between bacteria via conjugation and integrate into the host chromosome. SXT and related ICEs became prevalent in Asian Vibrio cholerae populations in the 1990s and play an important role in the dissemination of antibiotic resistance genes in V. cholerae.