Clinical Management of Infectious Contact Lens Complications
Treatment of biofilm and colonization is a de facto treatment of infection (reservoir and spread). Some options tested in preclinical and clinical trials are:
In the near future, drug-mediated genetic modifications of the biofilm may make embedded pathogens amenable to disinfectants and conventional antibiotics. Furthermore, biofilm dispersal by small aminoimidazole molecules, cationic peptides, and enzymes such as DNase and alginate lyase, as well as QS inhibitors, may facilitate biofilm-associated keratitis treatment success.
Contact lens materials have a varying propensity to develop a biofilm on their surfaces. Whereas hydrophobic acrylates develop biofilm most readily, hydrophobic silicones range between hydrophilic hydrogels and hydrophilic silicone elastomers in susceptibility. In experimental and clinical settings, when covalently linked to silicone hydrogel CLs, cationic peptides such as melimin have been found to promote the reduction or prevention of bacterial growth and infectious complications.
Enzymes that degrade biofilm matrix polymers have been shown to inhibit biofilm formation, detach established biofilm colonies and render biofilm cells sensitive to killing by antimicrobial agents. Biofilm matrix-degrading enzymes act as antibiofilm agents for the treatment and prevention of CL infections. Two enzymes, deoxyribonuclease I and the glycoside hydrolase dispersin B, have been found to be the best candidates.
Nano-modified coatings with selenium and iron oxide, which can penetrate into the biofilm and reach embedded pathogens, can prevent biofilm formation and microbial colonization. Nanoetching techniques can modify the topography of surfaces and inhibit bacterial adhesion.
2-Aminoimidazoles can inhibit and disperse the biofilms of various bacteria. Antibiotics combined with 2-aminoimidazole/triazole conjugates have been shown to disperse the biofilms of S. aureus, P. aeruginosa and Acinetobacter baumannii, and reestablish organism sensitivity to conventional antibiotics.
A PVP iodine solution, Bioclen FR One Step® (Ophthec Corp., FL, USA), used for soft CLs, has been shown to be active against relevant bacteria, fungi and certain strains of Acanthamoeba.
Several classes of biofilm inhibitors have been developed over the last decade. Potential uses include storage solution add-ons and co-applications with antibiotics in clinical settings. Halogenated furanones, derivatives of the Australian red macroalgae (seaweed) Delisea pulchra, which interfere with cyclic di-GMP, DNA and nucleotide biosynthesis, are possibly too toxic for clinical applications, whereas the RNAIII-inhibiting peptide may offer more practical technical and clinical uses, such as loading of polymethylmethacrylate to prevent biofilm formation by S. aureus and in vivo injections. QS antagonists function as blockers of pathogenicity, and do not block bacterial growth by themselves. Therefore, QS antagonists are believed not to develop bacterial resistance, and are biocompatible.
Treatment Outlook
Treatment of biofilm and colonization is a de facto treatment of infection (reservoir and spread). Some options tested in preclinical and clinical trials are:
Modifications of the physicochemical properties of the CL material;
Modifications of the physicochemical properties of the storage solution;
Microbicidal impregnation of storage box walls;
Nanoetching of lens and storage box walls;
Interference of microbial communication;
Enzyme treatment of the matrix;
Molecular penetration of the matrix and destruction of microbes;
Dispersal.
In the near future, drug-mediated genetic modifications of the biofilm may make embedded pathogens amenable to disinfectants and conventional antibiotics. Furthermore, biofilm dispersal by small aminoimidazole molecules, cationic peptides, and enzymes such as DNase and alginate lyase, as well as QS inhibitors, may facilitate biofilm-associated keratitis treatment success.
Modifications of Physicochemical Properties of the CL Material
Contact lens materials have a varying propensity to develop a biofilm on their surfaces. Whereas hydrophobic acrylates develop biofilm most readily, hydrophobic silicones range between hydrophilic hydrogels and hydrophilic silicone elastomers in susceptibility. In experimental and clinical settings, when covalently linked to silicone hydrogel CLs, cationic peptides such as melimin have been found to promote the reduction or prevention of bacterial growth and infectious complications.
Enzyme Treatment of Matrix
Enzymes that degrade biofilm matrix polymers have been shown to inhibit biofilm formation, detach established biofilm colonies and render biofilm cells sensitive to killing by antimicrobial agents. Biofilm matrix-degrading enzymes act as antibiofilm agents for the treatment and prevention of CL infections. Two enzymes, deoxyribonuclease I and the glycoside hydrolase dispersin B, have been found to be the best candidates.
Surface Nanotechnology
Nano-modified coatings with selenium and iron oxide, which can penetrate into the biofilm and reach embedded pathogens, can prevent biofilm formation and microbial colonization. Nanoetching techniques can modify the topography of surfaces and inhibit bacterial adhesion.
Aminoimidazoles
2-Aminoimidazoles can inhibit and disperse the biofilms of various bacteria. Antibiotics combined with 2-aminoimidazole/triazole conjugates have been shown to disperse the biofilms of S. aureus, P. aeruginosa and Acinetobacter baumannii, and reestablish organism sensitivity to conventional antibiotics.
PVP Iodine
A PVP iodine solution, Bioclen FR One Step® (Ophthec Corp., FL, USA), used for soft CLs, has been shown to be active against relevant bacteria, fungi and certain strains of Acanthamoeba.
QS Inhibitors
Several classes of biofilm inhibitors have been developed over the last decade. Potential uses include storage solution add-ons and co-applications with antibiotics in clinical settings. Halogenated furanones, derivatives of the Australian red macroalgae (seaweed) Delisea pulchra, which interfere with cyclic di-GMP, DNA and nucleotide biosynthesis, are possibly too toxic for clinical applications, whereas the RNAIII-inhibiting peptide may offer more practical technical and clinical uses, such as loading of polymethylmethacrylate to prevent biofilm formation by S. aureus and in vivo injections. QS antagonists function as blockers of pathogenicity, and do not block bacterial growth by themselves. Therefore, QS antagonists are believed not to develop bacterial resistance, and are biocompatible.
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