Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
Add more filters










Database
Language
Publication year range
2.
Int Forum Allergy Rhinol ; 9(12): 1470-1477, 2019 12.
Article in English | MEDLINE | ID: mdl-31461581

ABSTRACT

BACKGROUND: Manuka honey (MH) has significant antibiofilm activity in vitro and in vivo against Staphylococcus aureus, methicillin-resistant S aureus (MRSA), and Pseudomonas aeruginosa. This is the first randomized, single-blinded, placebo-controlled phase 1 clinical trial investigating the safety and preliminary efficacy of MH with augmented methylglyoxal (MGO) rinses in recalcitrant chronic rhinosinusitis (CRS). METHODS: Patients were included after previously undergoing endoscopic sinus surgery and presenting with signs and symptoms of sinus infection with positive bacterial cultures on sinus swabs. Patients were randomized to receive 14 days of twice-daily 16.5% MH + 1.3 mg/mL MGO sinonasal rinses and concurrent 10 days of placebo tablets (MH), or 14 days of twice-daily saline sinonasal rinses and concurrent 10 days of culture-directed antibiotic therapy (CON). Safety observations included the University of Pennsylvania Smell Identification Test (UPSIT) and adverse-event (AE) reporting. Efficacy was assessed comparing microbiology results, Lund-Kennedy scores (LKSs), and symptom scores using the visual analog scale (VAS) and 22-item Sino-Nasal Outcome Test (SNOT-22). RESULTS: Twenty-five patients completed the study. MH demonstrated a good safety profile with no major AEs and no changes in UPSIT. Six of 10 (60%) MH patients had a reduction in bacterial culture rate with 1 of 10 of those having negative cultures, compared with 12 of 15 (80%) in the control group with 7 of 15 having negative cultures upon completion of the study. CONCLUSION: This study concludes that twice-daily 16.5% MH augmented with 1.3 mg/mL MGO sinonasal rinses alone for 14 days is safe but not superior to culture-directed oral antibiotics and twice-daily saline rinses.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Apitherapy , Honey , Rhinitis/therapy , Sinusitis/therapy , Adult , Aged , Aged, 80 and over , Bacteria/isolation & purification , Chronic Disease , Female , Humans , Leptospermum , Male , Middle Aged , Nasal Lavage , Paranasal Sinuses/microbiology , Rhinitis/microbiology , Single-Blind Method , Sinusitis/microbiology
3.
JAMA Otolaryngol Head Neck Surg ; 145(8): 723-729, 2019 Aug 01.
Article in English | MEDLINE | ID: mdl-31219531

ABSTRACT

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. DESIGN, SETTING, AND PARTICIPANTS: This phase 1, first-in-humans, open-label clinical trial of multiple ascending doses was conducted at a single tertiary referral center from December 1, 2015, through September 30, 2016, with follow-up completed on December 31, 2016. Patients with recalcitrant CRS (aged 18-70 years) in whom surgical and medical treatment had failed and who had positive S aureus cultures sensitive to AB-SA01 were recruited. Findings were analyzed from February 2 through August 31, 2017. INTERVENTIONS: Three patient cohorts (3 patients/cohort) received serial doses of twice-daily intranasal irrigations with AB-SA01 at a concentration of 3 × 108 plaque-forming units (PFU) for 7 days (cohort 1), 3 × 108 PFU for 14 days (cohort 2), and 3 × 109 PFU for 14 days (cohort 3). MAIN OUTCOMES AND MEASURES: The primary study outcome was the safety and tolerability of intranasal AB-SA01. Safety observations included vital signs, physical examinations, clinical laboratory test results, and adverse events. The secondary outcome was preliminary efficacy assessed by comparing pretreatment and posttreatment microbiology results, disease-relevant endoscopic Lund-Kennedy Scores, and symptom scores using a visual analog scale and Sino-Nasal Outcome Test-22. RESULTS: All 9 participants (4 men and 5 women; median age, 45 years [interquartile range, 41.0-71.5 years]) completed the trial. Intranasal phage treatment was well tolerated, with no serious adverse events or deaths reported in any of the 3 cohorts. No change in vital signs occurred before and 0.5 and 2.0 hours after administration of AB-SA01 and at the exit visit. No changes in biochemistry were found except for 1 participant in cohort 3 who showed a decrease in blood bicarbonate levels on exit visit, with normal results of physical examination and vital signs. All biochemistry values were normalized 8 days later. No changes in temperature were recorded before, during, or after treatment. Six adverse effects were reported in 6 participants; all were classified as mild treatment-emergent adverse effects and resolved by the end of the study. Preliminary efficacy results indicated favorable outcomes across all cohorts, with 2 of 9 patients showing clinical and microbiological evidence of eradication of infection. CONCLUSIONS AND RELEVANCE: Intranasal irrigation with AB-SA01 of doses to 3 × 109 PFU for 14 days was safe and well tolerated, with promising preliminary efficacy observations. Phage therapy could be an alternative to antibiotics for patients with CRS. TRIAL REGISTRATION: http://anzctr.org.au identifier: ACTRN12616000002482.

4.
Sci Rep ; 9(1): 2378, 2019 02 20.
Article in English | MEDLINE | ID: mdl-30787349

ABSTRACT

Normal wound healing is a highly regulated and coordinated process. However, tissue injury often results in inflammation with excessive scar tissue formation after 40-70% of operations. Here, we evaluated the effect of the iron chelator deferiprone on inflammation and the migration of primary nasal fibroblasts and primary human nasal epithelial cells (HNECs) in vitro. The cytotoxicity of deferiprone was examined by the lactate dehydrogenase assay on primary nasal fibroblasts and air-liquid interface (ALI) cultures of HNECs. Wound closure was observed in scratch assays by using time-lapse confocal scanning laser microscopy. Interleukin-6 (IL-6) and type I and III collagen protein levels were determined by ELISA. Intracellular Reactive Oxygen Species (ROS) activity was measured by utilizing the fluorescent probe H2DCFDA. Deferiprone at 10 mM concentration was non-toxic to primary fibroblasts and HNECs for up to 48 hours application. Deferiprone had significant dose-dependent inhibitory effects on the migration, secreted collagen production and ROS release by primary nasal fibroblasts. Deferiprone blocked Poly (I:C)-induced IL-6 production by HNECs but did not alter their migration in scratch assays. Deferiprone has the potential to limit scar tissue formation and should be considered in future clinical applications.


Subject(s)
Anti-Inflammatory Agents , Cell Movement/drug effects , Deferiprone , Fibroblasts/drug effects , Inflammation/drug therapy , Wound Healing/drug effects , Adult , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology , Cell Proliferation/drug effects , Cells, Cultured , Collagen Type I/metabolism , Collagen Type II/metabolism , Deferiprone/administration & dosage , Deferiprone/pharmacology , Female , Fibroblasts/cytology , Humans , Interleukin-6/metabolism , Iron Chelating Agents/administration & dosage , Iron Chelating Agents/pharmacology , Male , Middle Aged , Paranasal Sinuses/cytology , Reactive Oxygen Species/metabolism
5.
Transl Res ; 206: 41-56, 2019 04.
Article in English | MEDLINE | ID: mdl-30615845

ABSTRACT

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. The aims of this study were to assess the safety and efficacy of a PA phage cocktail (CT-PA) in a sheep model of rhinosinusitis. The sheep rhinosinusitis model was adapted to simulate PA infection in sheep frontal sinuses. To assess efficacy, after a 7-day biofilm formation period, sheep received twice-daily frontal trephine flushes of CT-PA or saline for 1 week. Biofilm quantitation on frontal sinus mucosa was performed using LIVE/DEAD BacLight staining. To assess safety, sheep received twice-daily frontal trephine flushes of CT-PA or vehicle control for 3 weeks. Blood and fecal samples were collected throughout treatment. Histopathology of frontal sinus, lung, heart, liver, spleen, and kidney tissue was performed. Sinus cilia were visualized using scanning electron microscopy (SEM). The Efficacy arm showed a statistically significant reduction in biofilm biomass with all concentrations of CT-PA tested (P < 0.05). Phage presence in sinuses was maintained for at least 16hours after the final flush. All Safety arm sheep completed 3 weeks of treatment. Phage was detected consistently in feces and sporadically in blood and organ samples. Histology and SEM of tissues revealed no treatment-related damage. In conclusion, CT-PA was able to decrease sinus PA biofilm at concentrations of 108-1010 PFU/mL. No safety concerns were noted.


Subject(s)
Bacteriophages/physiology , Pseudomonas aeruginosa/isolation & purification , Sinusitis/microbiology , Animals , Pseudomonas aeruginosa/pathogenicity , Sheep
SELECTION OF CITATIONS
SEARCH DETAIL
...