Antibacterial activity of a new broad-spectrum antibiotic covalently bound to titanium surfaces.

Abstract

Biofilm-associated infections, particularly those caused by Staphylococcus aureus, are a major cause of implant failure. Covalent coupling of broad-spectrum antimicrobials to implants is a promising approach to reduce the risk of infections. In this study, we developed titanium substrates on which the recently discovered antibacterial agent SPI031, a N-alkylated 3, 6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol, was covalently linked (SPI031-Ti). We found that SPI031-Ti substrates prevent biofilm formation of S. aureus and Pseudomonas aeruginosa in vitro, as quantified by plate counting and fluorescence microscopy. To test the effectiveness of SPI031-Ti substrates in vivo, we used an adapted in vivo biomaterial-associated infection model in mice in which SPI031-Ti substrates were implanted subcutaneously and subsequently inoculated with S. aureus. Using this model, we found a significant reduction in biofilm formation (up to 98%) on SPI031-Ti substrates compared to control substrates. Finally, we demonstrated that the functionalization of the titanium surfaces with SPI031 did not influence the adhesion and proliferation of human cells important for osseointegration and bone repair. In conclusion, these data demonstrate the clinical potential of SPI031 to be used as an antibacterial coating for implants, thereby reducing the incidence of implant-associated infections. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2191-2198, 2016.

• Authors: Evelien Gerits, Soňa Kucharíková, Patrick Van Dijck, Martin Erdtmann, Annika Krona, Maria Lövenklev, Mirjam Fröhlich, Barbara Dovgan, Frédéric Impellizzeri, Annabel Braem, Jef Vleugels, Stijn C A Robijns, Hans P Steenackers, Jozef Vanderleyden, Katrijn De Brucker, Karin Thevissen, Bruno P A Cammue, Maarten Fauvart, Natalie Verstraeten, Jan Michiels
• Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society (J Orthop Res) Vol. 34 Issue 12 Pg. 2191-2198 (12 2016) ISSN: 1554-527X [Electronic] United States
• PMID: 27003909 (Publication Type: Journal Article)
• Copyright: © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Chemical References

• Anti-Infective Agents
• Carbazoles
• SPI031
• Titanium

Topics

• Animals
• Anti-Infective Agents (pharmacology, therapeutic use)
• Carbazoles (pharmacology, therapeutic use)
• Cell Adhesion (drug effects)
• Cell Proliferation (drug effects)
• Female
• Mice, Inbred BALB C
• Microbial Sensitivity Tests
• Prosthesis-Related Infections (prevention & control)
• Pseudomonas aeruginosa (drug effects)
• Staphylococcus aureus (drug effects)
• Titanium