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.

Elucidation of the Mode of Action of a New Antibacterial Compound Active against Staphylococcus aureus and Pseudomonas aeruginosa

“…Moreover, additional tests demonstrated antibacterial activity against a representative selection of ESKAPE pathogens (see S5 Table ). Furthermore, we demonstrated that SPI031-functionalised titanium surfaces show significant antibacterial activity both in vitro and in vivo [ 17 ].…”

“…In addition, we showed that the compound displays antifungal activity against Candida albicans [ 16 ]. Furthermore, we demonstrated that SPI031 has the clinical potential to be used as an antibacterial coating for implants, thereby reducing the incidence of implant-associated infections [ 17 ]. In the present study, we further investigated the antibacterial characteristics, including bactericidal activity and spontaneous resistance frequency, and mode of action of SPI031 using S .…”

Review of titanium surface modification techniques and coatings for antibacterial applications

“…The "grafting to" strategy permits an indirect grafting thanks to anchor molecules (silane [114][115][116][117], catechol [118][119][120][121], phosphate [122][123][124][125]). It enables titanium functionalization with various molecules in order to confer customized properties (Scheme 2).…”

“…Gerits et al [116] developed titanium substrates on which the recently discovered antibacterial agent SPI031, an N-alkylated 3, 6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9yl)propan-2-ol, was covalently linked (SPI031-Ti) via a silane anchor (3-aminopropyl-triethoxy silane). They found that SPI031-Ti substrates prevent biofilm formation of S. aureus and P. aeruginosainvitro.…”

Bioceramic Layers with Antifungal Properties

“…These facts have accentuated the pressing need to work towards developing new implants less susceptible to infections. Over the last decades, measures have been implemented to reduce the number of implant related infections by defining and putting into effect strict hygienic routines in the operating rooms and by using perioperative antibiotic prophylaxis [1][2][3][4][5][6][7][8][9]. Nevertheless, because the incidence of implant-related infections has continued to increase, the attention of scientists has focused on the development of newly biocompatible and antimicrobial materials that can be used as coatings for implantable medical devices [10,11].…”