High-dose versus standard-dose amoxicillin/clavulanate for clinically-diagnosed acute bacterial sinusitis: A randomized clinical trial.

BACKGROUND: The recommended treatment for acute bacterial sinusitis in adults, amoxicillin with clavulanate, provides only modest benefit. OBJECTIVE: To see if a higher dose of amoxicillin will lead to more rapid improvement. DESIGN, SETTING, AND PARTICIPANTS: Double-blind randomized trial in which, from November 2014 through February 2017, we enrolled 315 adult outpatients diagnosed with acute sinusitis in accordance with Infectious Disease Society of America guidelines. INTERVENTIONS: Standard-dose (SD) immediate-release (IR) amoxicillin/clavulanate 875 /125 mg (n = 159) vs. high-dose (HD) (n = 156). The original HD formulation, 2000 mg of extended-release (ER) amoxicillin with 125 mg of IR clavulanate twice a day, became unavailable half way through the study. The IRB then approved a revised protocol after patient 180 to provide 1750 mg of IR amoxicillin twice a day in the HD formulation and to compare Time Period 1 (ER) with Time Period 2 (IR). MAIN MEASURE: The primary outcome was the percentage in each group reporting a major improvement-defined as a global assessment of sinusitis symptoms as "a lot better" or "no symptoms"-after 3 days of treatment. KEY RESULTS: Major improvement after 3 days was reported during Period 1 by 38.8% of ER HD versus 37.9% of SD patients (P = 0.91) and during Period 2 by 52.4% of IR HD versus 34.4% of SD patients, an effect size of 18% (95% CI 0.75 to 35%, P = 0.04). No significant differences in efficacy were seen at Day 10. The major side effect, severe diarrhea at Day 3, was reported during Period 1 by 7.4% of HD and 5.7% of SD patients (P = 0.66) and during Period 2 by 15.8% of HD and 4.8% of SD patients (P = 0.048). CONCLUSIONS: Adults with clinically diagnosed acute bacterial sinusitis were more likely to improve rapidly when treated with IR HD than with SD but not when treated with ER HD. They were also more likely to suffer severe diarrhea. Further study is needed to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02340000.

Testing the role of charge and structure on the stability of peptide-porphyrin complexes.

This study aims to extend a structural and biophysical understanding of a coiled-coil based peptide model system that serves as a scaffold for the anionic porphyrin, TPPS4. This is part of an ongoing biomaterials effort to create photoelectronically active mesoscale fibrils for surface deposition and characterization of conductivity properties. The goals are two-fold: (1) to explore optimal basic side-chain moieties for tight binding to TPPS4 and (2) to test the binding of various metalated TPPS4 derivatives to our peptide model system. The latter goal is to control the electronic and redox properties of the fibrillar biomaterials. A soluble version of the peptide biomaterial was used in order to probe binding and to extract thermodynamically rigorous equilibrium binding constants. UV-visible spectroscopy and circular dichroism spectropolarimtery are used to measure the effects of binding on the Soret band of the porphyrin and the helical signal of the peptide, respectively. For the first study, it was found that lysine, ornithine, and arginine are equally robust at engaging TPPS4 with low micromolar binding affinity. In the case of the metalated porphyrins, submicromolar binding affinity was observed for Cu(II), Ni(II), and Pd(II). The ability of these metalated porphyrins to bind with high affinity is dependent largely on structural perturbations of the porphyrin molecule, rather than on induced electronic effects.