The Noncovalent Bonding of Antibiotics to a Polytetrafluoroethylene -Benzalkonium Graft

Harvey, Richard A.; Greco, Ralph S.

doi:10.1097/00000658-198111000-00015

Cited by 50 publications

(6 citation statements)

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“…A great diversity of antibiotics used for reasonable graft protection are described in the literature, including penicillins (18), fluoroquinolones (29), and aminoglycosides (27 (25) claim to achieve a less toxic and less thrombogenic effect by binding antibiotics directly or in combination with a metal such as silver to the surface of a graft; however, this method limits both the quantity of drug on the graft surface and the development of a slow drug release system.…”

Section: Discussionmentioning

confidence: 99%

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New Anti-Infective Coatings of Medical Implants

Matl

Obermeier

Repmann³

et al. 2008

Antimicrob Agents Chemother

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Implantable devices are highly susceptible to infection and are therefore a major risk in surgery. The present work presents a novel strategy to prevent the formation of a biofilm on polytetrafluoroethylene (PTFE) grafts. PTFE grafts were coated with gentamicin and teicoplanin incorporated into different lipid-like carriers under aseptic conditions in a dipping process. Poly-D,L-lactic acid, tocopherol acetate, the diglyceride Softisan 649, and the triglyceride Dynasan 118 were used as drug carriers. The drug release kinetics, anti-infective characteristics, biocompatibility, and hemocompatibility of the coatings developed were studied. All coatings showed an initial drug burst, followed by a low continuous drug release over 96 h. The dimension of release kinetics depended on the carrier used. All coated prostheses reduced bacterial growth drastically over 24 h, even below pathologically relevant concentrations. Different cytotoxic levels could be observed, revealing tocopherol acetate as the most promising biocompatible carrier. A possible reason for the highly cytotoxic effect of Softisan 649 could be assessed by demonstrating incorporated lipids in the cell soma with Oil Red O staining. Tromboelastography studies, enzyme-linked immunosorbent assays, and an amidolytic substrate assay could confirm the hemocompatibility of individual coatings. The development of the biodegradable drug delivery systems described here and in vitro studies of those systems highlight the most important requirements for effective as well as compatible anti-infective coatings of PTFE grafts. Through continuous local release, high drug levels can be produced at only the targeted area and physiological bacterial proliferation can be completely inhibited, while biocompatibility as well as hemocompatibility can be ensured.A major risk associated with surgical placement of medical implants such as endoprostheses or vascular prostheses is their high infection rate (4,8). This is not only of prime importance for the patient but also imposes a high financial cost on the economy (21). Synthetic vascular grafts such as polytetrafluoroethylene (PTFE) prostheses are easily accessible to pathogens, mostly Staphylococcus aureus and Staphylococcus epidermidis. These pathogens colonize the implant by adhering to the patient's own proteins located on the surface of the graft and form a biofilm (1,14,16,23,34). The formation of biofilms on biomaterials presents challenging complications in the field of medical implants (2,12,24,28,30). In a biofilm, bacteria are well protected from the host immune defense. An increase in antibiotic resistance is the consequence (6,8,35); even high local concentrations of antibiotics do not completely eradicate bacteria in biofilms (8, 10). It is therefore of great importance to prevent bacterial adhesion on vascular grafts (7). This can be achieved by antibiotic surface coatings.There have been several approaches to equipping vascular grafts with anti-infective agents to prevent bacterial colonization. Different antim...

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Section: Discussionmentioning

confidence: 99%

“…A common method used to bind hydrophilic drugs onto the lipophilic surfaces of PTFE grafts is the use of surfactantmediated agents, e.g., benzalkonium chloride (15,18) or tridodecylmethylammonium chloride (17). Another method of drug binding is the incorporation of drugs into biodegradable polymer carriers (13).…”

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confidence: 99%

New Anti-Infective Coatings of Medical Implants

Matl

Obermeier

Repmann³

et al. 2008

Antimicrob Agents Chemother

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“…A number of attempts have been made to attach an antimicrobial agent such as an antibiotic (6,9,12), quaternary ammonium compound (3,8,27), hexachlorophene (2), or iodide (26) to an insoluble matrix. These products were intended to be used as water disinfectants, as antimicrobial surfaces, or for investigations of the mechanism of action of drugs.…”

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confidence: 99%

Antimicrobial activity of tertiary amine covalently bonded to a polystyrene fiber

Endo

Tani

Kodama

1987

Appl Environ Microbiol

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Tertiary amine was covalently bonded to a polystyrene fiber and examined for antibacterial activity. The tertiary amine covalently bonded to a polystyrene fiber (TAF) showed a high antimicrobial activity against Escherichia coli. TAF exhibited a stronger antibacterial activity against gram-negative bacteria (E. coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhimurium, and Serratia marcescens) than against gram-positive bacteria (Staphylococcus aureus and Streptococcus faecalis) or Candida albicans. This activity against E. coli was accentuated by 0.1% deoxycholate or 10 mg of actinomycin D per ml, to which E. coli is normally not susceptible. This implies that TAF causes an increase of the bacterial outer membrane permeability. On the other hand, the antimicrobial activity was inhibited by adding Mg2+ or by lowering the pH. This suggests an electrostatic interaction between the bacterial cell wall and TAF. Scanning electron microscopy showed that E. coli cells were initially attached to TAF, with many projections on the cell surface, but then were apparently lysed after contact for 4 h. Taken together, these results imply that bacteria initially interact with TAF by an electrostatic force between the anionic bacterial outer membrane and the cationic tertiary amine residues of TAF and that longer contact with TAF damages the bacterial outer membrane structure and increases its permeability.

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“…Synthetic vascular grafts such as polytetrafluoroethylene (PFTE) prostheses are easily accessible to pathogens after inserted into the patient. The lipophilicity of these PTFE grafts has been modulated with benzalkonium chloride (Harvey & Greco, 1981;Greco et al, 1982) or tridodecylmethylammonium chloride , or incorporating drugs into biodegradable polymer carriers (Gollwitzer et al, 2003). Recently, new lipid-based formulations to incorporate antibiotics for anti-infective action in grafts were developed.…”

Section: Wwwintechopencommentioning

confidence: 99%