Preliminary Results of the Use of a Stabilized Hypochlorous Acid Solution in the Management of Ralstonia Pickettii Biofilm on Silicone Breast Implants.

Background: Ralstonia Pickettii biofilms are associated with pocket infections following breast implant surgeries. Biofilm protects bacteria most topically applied antimicrobial irrigations.

Objectives: To evaluate the effectiveness of four antimicrobial solutions on the planktonic form and established biofilm of Ralstonia Pickettii grown on 3 different types of silicone breast implants.

Toxicity modulation, resistance enzyme evasion, and A-site X-ray structure of broad-spectrum antibacterial neomycin analogs.

Aminoglycoside antibiotics are pseudosaccharides decorated with ammonium groups that are critical for their potent broad-spectrum antibacterial activity. Despite over three decades of speculation whether or not modulation of pKa is a viable strategy to curtail aminoglycoside kidney toxicity, there is a lack of methods to systematically probe amine-RNA interactions and resultant cytotoxicity trends. This study reports the first series of potent aminoglycoside antibiotics harboring fluorinated N1-hydroxyaminobutyryl acyl (HABA) appendages for which fluorine-RNA contacts are revealed through an X-ray cocrystal structure within the RNA A-site.

Toward Overcoming Staphylococcus aureus Aminoglycoside Resistance Mechanisms with a Functionally Designed Neomycin Analogue.

Deoxygenation of the diol groups in rings A and D of neomycin in combination with the introduction of an N1-(l)-HABA group in the 2-deoxystreptamine subunit (ring B) leads to a novel and potent antibiotic (1) with activity against strains of S. aureus carrying known aminoglycoside resistance determinants, as well as against an extended panel of Methicillin-resistant S. aureus isolates (n = 50).

Hybrid aminoglycoside antibiotics via Tsuji palladium-catalyzed allylic deoxygenation.

Biosynthetically inspired manipulation of the antibiotic paromomycin led, in six high-yielding steps, to a ring A harboring an α,β-unsaturated 6'-aldehyde and an allylic 3'-methylcarbonate group. Tsuji deoxygenation in the presence of 5 mol % Pd(2)(dba)(3) and Bu(3)P granted access to a novel series of 3',4'-dideoxy-4',5'-dehydro ring A hybrids. The neomycin-sisomicin hybrid exhibited superior in vitro antibacterial activity to the parent compound neomycin.

Synthesis and spectrum of the neoglycoside ACHN-490.

ACHN-490 is a neoglycoside, or "next-generation" aminoglycoside (AG), that has been identified as a potentially useful agent to combat drug-resistant bacteria emerging in hospitals and health care facilities around the world. A focused medicinal chemistry campaign produced a collection of over 400 sisomicin analogs from which ACHN-490 was selected. We tested ACHN-490 against two panels of Gram-negative and Gram-positive pathogens, many of which harbored AG resistance mechanisms.