Activities of Bismuth Thiols against Staphylococci and Staphylococcal Biofilms

Abstract

Indwelling medical devices are associated with infectious complications. Incorporating antimicrobials into indwelling materials may reduce bacterial colonization. Bismuth thiols are antibiofilm agents with up to 1,000-fold-greater antibacterial activity than other bismuth salts. Staphylococci are particularly sensitive, as determined by agar diffusion and broth dilution susceptibility testing. Bismuth-ethanedithiol inhibited 10 methicillin-resistant Staphylococcus epidermidis strains at 0.9 to 1.8, Staphylococcus aureus ATCC 25923 at 2.4, and S. epidermidis ATCC 12228 at 0.1 M Bi 3؉ . Antiseptic-resistant S. aureus was sensitive to bismuth-2-3-dimercaptopropanol (BisBAL) at <7 M Bi 3؉ . Hydrogel-coated polyurethane rods soaked in BisBAL inhibited S. epidermidis for 39 days (inhibitory zone diameter in agar, >30 mm for >25 days). Slime from 16 slimeproducing S. epidermidis strains was inhibited significantly by bismuth-3,4-dimercaptotoluene (BisTOL), but not by AgNO 3 , at subinhibitory concentrations. In conclusion, bismuth-thiols are bacteriostatic and bactericidal against staphylococci, including resistant organisms, but are also inhibitors of slime at subinhibitory concentrations. At subinhibitory concentrations, BisTOL may be useful in preventing the colonization and infection of indwelling intravascular lines, since staphylococci are important pathogens in this setting.

Vancomycin-Modified Implant Surface Inhibits Biofilm Formation and Supports Bone-Healing in an Infected Osteotomy Model in Sheep

“…We used a high bacterial load of Staphylococcus aureus ATCC 25923, a clinical isolate and a standard strain that is reported to form biofilms [39][40][41][42][43][44] . Staphylococcus aureus is the most common causative agent in periprosthetic infection [42][43][44][45][46] , and approximately 56% of clinical isolates of Staphylococcus aureus formed biofilms in one study 44 .…”

The Action of Bismuth against Helicobacter pylori Mimics but Is Not Caused by Intracellular Iron Deprivation

“…Iron is required for growth because it is a cofactor for many essential enzymatic processes (42), and many of the observed effects of bismuth on bacteria could be the result of iron limitation. These effects include a reduction in intracellular ATP levels (44), inhibition of protein and cell wall synthesis and of membrane function (32), and a reduction in capsular polysaccharide production (19,20,22,28).A reduction in outer membrane lipopolysaccharide (LPS) expression occurs when H. pylori is deprived of iron (J. Keenan, unpublished data), whereas several iron-repressible outer membrane proteins are concomitantly up-regulated (18, 29, 52). These observations led us to hypothesize that the antimicrobial action of bismuth could be due to it competitively inhibiting iron uptake.…”

“…Iron is required for growth because it is a cofactor for many essential enzymatic processes (42), and many of the observed effects of bismuth on bacteria could be the result of iron limitation. These effects include a reduction in intracellular ATP levels (44), inhibition of protein and cell wall synthesis and of membrane function (32), and a reduction in capsular polysaccharide production (19,20,22,28).…”

Antibacterial Properties of Some Cyclic Organobismuth(III) Compounds

“…Since the 1990s, the physiological aspect of bismuth chemistry has received considerable attention, and much effort has been devoted to the synthesis of different types of bismuth compounds in order to improve their antibacterial activities (2,(4)(5)(6)10). Pharmacological investigation of new bismuth compounds has led to the development of medications with interesting activities for the treatment of infectious diseases.…”