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 microM Bi(3+). Antiseptic-resistant S. aureus was sensitive to bismuth-2-3-dimercaptopropanol (BisBAL) at < or = 7 microM Bi(3+). Hydrogel-coated polyurethane rods soaked in BisBAL inhibited S. epidermidis for 39 days (inhibitory zone diameter in agar, > or = 30 mm for > 25 days). Slime from 16 slime-producing S. epidermidis strains was inhibited significantly by bismuth-3,4-dimercaptotoluene (BisTOL), but not by AgNO3, 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.

FIG. 1

Inhibitory action of BisBAL-coated polyurethane rods. Hydrogel-coated rods were soaked in 50 or 75 mM BisBAL overnight and embedded int agar plates seeded with S. epidermidis (■) or E. coli (●). Rods without BisBAL were also tested against S. epidermidis (▴) and E. coli (⧫). The plates were incubated overnight at 37°C, and the zones of inhibition were measured. The rods were transferred daily to fresh plates. Zone diameters are expressed as the means of three samples. The diameter of the rod was 3 mm, which was equivalent to no zone.

FIG. 2

Effect of BisTOL on growth (solid bars) and on biofilm formation (stippled bars) by S. epidermidis RP62A after 24 (A) and 48 (B) h. Bacteria adhering to microtiter plates were stained and measured for absorbence as described in Materials and Methods. The values are means of triplicate determinations (± standard deviations).