Exebacase for Staphylococcus aureus bloodstream infection and endocarditis

BACKGROUND: Novel therapeutic approaches are critically needed for Staphylococcus aureus bloodstream infections (BSI), particularly for methicillin-resistant S. aureus (MRSA). Exebacase, a first-in-class antistaphylococcal lysin, is a direct lytic agent that is rapidly bacteriolytic, eradicates biofilms, and synergizes with antibiotics. METHODS: In this superiority-design study, we randomly assigned 121 patients with S. aureus BSI/endocarditis to receive a single dose of exebacase or placebo. All patients received standard-of-care antibiotics. The primary efficacy endpoint was clinical outcome (responder rate) at Day 14. RESULTS: Clinical responder rates at Day 14 were 70.4% and 60.0% in the exebacase + antibiotics and antibiotics alone groups, respectively (difference=10.4, 90% CI [-6.3, 27.2], p-value=0.31), and were 42.8 percentage points higher in the pre-specified exploratory MRSA subgroup (74.1% vs. 31.3%, difference=42.8, 90% CI [14.3, 71.4], ad hoc p value=0.01). Rates of adverse events (AEs) were similar in both groups. No AEs of hypersensitivity to exebacase were reported. Thirty-day all-cause mortality rates were 9.7% and 12.8% in the exebacase + antibiotics and antibiotics alone groups, respectively, with a notable difference in MRSA (3.7% vs. 25.0%, difference= -21.3, 90% CI [-45.1, 2.5], ad hoc p-value=0.06). Among MRSA patients in the United States, median length-of-stay was 4-days shorter and 30-day hospital readmission rates were 48 percentage points lower in the exebacase-treated group compared with antibiotics alone. CONCLUSIONS: This study establishes proof-of-concept for exebacase and direct lytic agents as potential therapeutics and supports conduct of a confirmatory study focused on exebacase to treat MRSA BSI

Nanostructured thin films of TiO2 tailored by anodization

Although nanostructured TiO _2 layers have been widely prepared by anodization, thin films with thicknesses under 1 μ m, over substrate other than Ti foils, with structures beyond the nanopores, had remained a challenge. In this work, such nanostructured TiO _2 thin films were synthesized by anodization of Ti films deposited by sputtering on FTO/glass substrates. Anodization was performed in an electrolyte based on 0.6 wt% of NH _4 F, a graphite cathode and the application of 30 V during lapses ranging from 3 to 14 min. The amorphous TiO _2 structures acquired the crystal anatase phase after a post-annealing treatment at 450 °C/4 h. Porous morphologies were observed for anodizing times of 3 and 4 min, sponges were formed with 5 and 6 min and vertical tubular structures were achieved by using 7 up to 9 min; dissolution was observed for longer times. Pore diameters of the structures were in the range of 27 to 47 nm, lengths were within the 330 and 1000 nm interval, transmittance was in the visible range of 70 ± 10%, the energy gap was 3.37 ± 0.02 eV and the wet contact angle was between 20 to 27°. One major contribution of the findings herein developed, is that they can be extended to TiO _2 thin films, with a specific nanostructure, grown on a wide gamma of substrates, relevant for particular applications