Safety and Tolerability of Bacteriophage Therapy for Chronic Rhinosinusitis Due to Staphylococcus aureus.

Importance: Staphylococcus aureus infections are associated with recalcitrant chronic rhinosinusitis (CRS). The emerging threat of multidrug-resistant S aureus infections has revived interest in bacteriophage (phage) therapy.

Objective: To investigate the safety, tolerability, and preliminary efficacy of ascending multiple intranasal doses of investigational phage cocktail AB-SA01 in patients with recalcitrant CRS due to S aureus.

Safety and efficacy of a bacteriophage cocktail in an in vivo model of Pseudomonas aeruginosa sinusitis.

Pseudomonas aeruginosa (PA) is a bacterial pathogen that frequently displays antibiotic resistance. Its presence within the sinuses of chronic rhinosinusitis sufferers is associated with poorer quality of life. Obligately lytic bacteriophages (phages) are viruses that infect, replicate within, and lyse bacteria, causing bacterial death.

In vitro characteristics of an airway barrier-disrupting factor secreted by Staphylococcus aureus.

Background: Staphylococcus aureus is a major contributor to the pathophysiology of chronic rhinosinusitis (CRS). Previous research has shown that S. aureus-secreted products disrupt the airway barrier.

from patients with chronic rhinosinusitis show minimal genetic association between polyp and non-polyp phenotypes.

Background: has a high prevalence in chronic rhinosinusitis (CRS) patients and is suggested to play a more etiopathogenic role in CRS patients with nasal polyps (CRSwNP), a severe form of the CRS spectrum with poorer surgical outcomes. We performed a microbial genome-wide association study (mGWAS) to investigate whether isolates from CRS patients have particular genetic markers associated with CRS with nasal polyps (CRSwNP) or CRS without nasal polyps (CRSsNP).

Methods: Whole genome sequencing was performed on isolates collected from 28 CRSsNP and 30 CRSwNP patients.

Safety and Efficacy of Topical Chitogel- Deferiprone-Gallium Protoporphyrin in Sheep Model.

Increasing antimicrobial resistance has presented new challenges to the treatment of recalcitrant chronic rhinosinusitis fuelling a continuous search for novel antibiofilm agents. This study aimed to assess the safety and efficacy of Chitogel (Chitogel®, Wellington New Zealand) combined with novel antibiofilm agents Deferiprone and Gallium Protoporphyrin (CG-DG) as a topical treatment against biofilms . To assess safety, 8 sheep were divided into two groups of 7 day treatments ( = 8 sinuses per treatment); (1) Chitogel (CG) with twice daily saline flush, and (2) CG-DG gel with twice daily saline flush.

Activity of Bacteriophages in Removing Biofilms of Isolates from Chronic Rhinosinusitis Patients.

infections are prevalent amongst chronic rhinosinusitis (CRS) sufferers. Many strains form biofilms, leading to treatment failure. Lytic bacteriophages (phages) are viruses that infect, replicate within, and lyse bacteria, causing bacterial death.

Chitosan Dextran gel as an anti adhesion agent in a postlaminectomy spinal sheep model.

Introduction: Post-operative peridural adhesions increase morbidity after neurosurgical procedures. Aim of this study is to assess safety and efficacy of Chitosan-Dextran (CD) gel as an anti-adhesion agent in a spinal laminectomy sheep model.

Methods: Eighteen sheep were used in this study with 6 animals in each treatment arm (namely, CD gel, Gelfoam paste and normal saline control).

Long-Term Safety of Topical Bacteriophage Application to the Frontal Sinus Region.

biofilms contribute negatively to a number of chronic conditions, including chronic rhinosinusitis (CRS). With the inherent tolerance of biofilm-bound bacteria to antibiotics and the global problem of bacterial antibiotic resistance, the need to develop novel therapeutics is paramount. Phage therapy has previously shown promise in treating sinonasal biofilms.

Reduced Innate Immune Response to a Small Colony Variant Compared to Its Wild-Type Parent Strain.

small colony variants (SCVs) can survive within the host intracellular milieu and are associated with chronic relapsing infections. However, it is unknown whether host invasion rates and immune responses differ between SCVs and their wild-type counterparts. This study used a stable SCV (WCH-SK2) developed from a clinical isolate (WCH-SK2) in inflammation-relevant conditions.

Association of intracellular Staphylococcus aureus with prognosis in chronic rhinosinusitis.

Background: Staphylococcus aureus (S. aureus) has been shown to exist within nasal epithelial cells in chronic rhinosinusitis (CRS) patients. This study investigates the localization of intracellular S.

Fighting sinus-derived Staphylococcus aureus biofilms in vitro with a bacteriophage-derived muralytic enzyme.

Background: Staphylococcus aureus biofilms are a nidus for exacerbation of infectious conditions including chronic rhinosinusitis (CRS). Resistance of biofilms to current therapeutics stresses the need for the development of novel anti-biofilm strategies. The chimeric muralytic enzyme P128 was specifically engineered to target Staphylococcal sp.

An in vivo safety and efficacy demonstration of a topical liposomal nitric oxide donor treatment for Staphylococcus aureus biofilm-associated rhinosinusitis.

The burden of drug resistance emerges in the wake of chronic and repeated antibiotic use. This underpins the importance of discovering alternatives to current antibiotic regimens. In chronic rhinosinusitis (CRS), topical therapy such as nasal douches and steroid sprays is the mainstay of treatment.

Topical colloidal silver as an anti-biofilm agent in a Staphylococcus aureus chronic rhinosinusitis sheep model.

Background: Treatment of recalcitrant chronic rhinosinusitis (CRS) is a challenge with increasing antibiotic resistance, leading to re-emergence of topical therapies. The aim of this study was to assess safety and efficacy of topical colloidal silver solution for the treatment of Staphylococcus aureus biofilms in a sheep model.

Methods: In the safety study, normal saline (control) and 30-ppm colloidal silver solution (test) was used to flush the frontal sinuses for 14 days in 8 sheep (4 sheep each).

Cousins, siblings, or copies: the genomics of recurrent Staphylococcus aureus infections in chronic rhinosinusitis.

Background: Staphylococcus aureus infection is known to play a role in recalcitrant chronic rhinosinusitis (CRS). However, it is unknown if recurrent S. aureus infections are caused by the same strain or are due to independent acquisitions of different strains.

Bacteriophage reduces biofilm of Staphylococcus aureus ex vivo isolates from chronic rhinosinusitis patients.

Background: Staphylococcus aureus is the most common organism in recalcitrant chronic rhinosinusitis (CRS) and is often resistant to traditional antibiotic therapy. Bacteriophages ("phages") are a potential candidate for a new, effective therapy. For phages to be useful in the setting of CRS, two minimum requirements must be presented: (1) phages must be effective against S.

Safety and efficacy of topical bacteriophage and ethylenediaminetetraacetic acid treatment of Staphylococcus aureus infection in a sheep model of sinusitis.

Background: Treatment of sinonasal bacterial biofilms continues to be a challenge in modern rhinology. This study's objective was to assess the safety and efficacy of topically applied Cocktail of S. aureus specific phage (CTSA) alone and in combination with ethylenediaminetetraacetic acid (EDTA) for treatment of Staphylococcus aureus biofilms in vivo.

Probiotic manipulation of the chronic rhinosinusitis microbiome.

Background: Staphylococcus aureus (SA) is a key pathogenic component of the chronic rhinosinusitis (CRS) microbiome and is associated with increased disease severity and poor postoperative outcomes. Probiotic treatments potentially offer a novel approach to the management of pathogenic bacteria in these recalcitrant patients through supporting a healthy community of commensal species. This study aims to investigate the probiotic properties of Staphylococcus epidermidis (SE) against SA in a mouse model of sinusitis.

Methylglyoxal-augmented manuka honey as a topical anti-Staphylococcus aureus biofilm agent: safety and efficacy in an in vivo model.

Background: Bacterial biofilms are thought to contribute to recalcitrance in chronic rhinosinusitis (CRS) patients. Manuka honey (MH) and its active component methylglyoxal (MGO) have demonstrated antibiofilm activity in vitro. This study evaluated the safety and efficacy of these agents in an in vivo model.

The efficacy and safety of chitosan dextran gel in a burr hole neurosurgical sheep model.

Background: Achieving and maintaining haemostasis is of paramount importance in neurosurgery. Chitosan has been shown in both animal and human models to be significantly effective in haemostasis as well as in reducing adhesion formation.

Objectives: To evaluate the haemostatic potential and to study histopathological changes caused by novel chitosan dextran gel in a neurosurgical sheep model.