The Antimicrobial Activity of Micron-Thin Sol–Gel Films Loaded with Linezolid and Cefoxitin for Local Prevention of Orthopedic Prosthesis-Related Infections

Orthopedic prosthesis-related infections (OPRI) are an essential health concern. OPRI prevention is a priority and a preferred option over dealing with poor prognosis and high-cost treatments. Micron-thin sol–gel films have been noted for a continuous and effective local delivery system. This study aimed to perform a comprehensive in vitro evaluation of a novel hybrid organic–inorganic sol–gel coating developed from a mixture of organopolysiloxanes and organophosphite and loaded with different concentrations of linezolid and/or cefoxitin. The kinetics of degradation and antibiotics release from the coatings were measured. The inhibition of biofilm formation of the coatings against Staphylococcus aureus, S. epidermidis, and Escherichia coli strains was studied, as well as the cell viability and proliferation of MC3T3-E1 osteoblasts. The microbiological assays demonstrated that sol–gel coatings inhibited the biofilm formation of the evaluated Staphylococcus species; however, no inhibition of the E. coli strain was achieved. A synergistic effect of the coating loaded with both antibiotics was observed against S. aureus. The cell studies showed that the sol–gels did not compromise cell viability and proliferation. In conclusion, these coatings represent an innovative therapeutic strategy with potential clinical use to prevent staphylococcal OPRI.

[1]  R. Shamma,et al.  Novel linezolid loaded bio-composite films as dressings for effective wound healing: experimental design, development, optimization, and antimicrobial activity , 2022, Drug delivery.

[2]  M. Monclús,et al.  Influence of Addition of Antibiotics on Chemical and Surface Properties of Sol-Gel Coatings , 2022, Materials.

[3]  S. Tecco,et al.  Elastodontic Devices in Orthodontics: An In-Vitro Study on Mechanical Deformation under Loading , 2022, Bioengineering.

[4]  J. Ahmed,et al.  Ag nanoparticle-decorated chitosan/SrSnO3 nanocomposite for ultrafast elimination of antibiotic linezolid and methylene blue , 2022, Environmental Science and Pollution Research.

[5]  M. Basiaga,et al.  Perspectives in Prevention of Biofilm for Medical Applications , 2022, Coatings.

[6]  J. Ahmed,et al.  Rapid photodegradation of linezolid antibiotic and methylene blue dye over Pt nanoparticles/polypyrrole-carbon black/ZnO novel visible light photocatalyst , 2021, Journal of Environmental Chemical Engineering.

[7]  F. Mulero,et al.  A New Antifungal-Loaded Sol-Gel Can Prevent Candida albicans Prosthetic Joint Infection , 2021, Antibiotics.

[8]  M. Catauro,et al.  Characterization of Hybrid Materials Prepared by Sol-Gel Method for Biomedical Implementations. A Critical Review , 2021, Materials.

[9]  B. Kumari,et al.  Sol-gel: Uncomplicated, routine and affordable synthesis procedure for utilization of composites in drug delivery: Review , 2021, Journal of Composites and Compounds.

[10]  I. Stockley,et al.  The antimicrobial activity and biocompatibility of a controlled gentamicin-releasing single-layer sol-gel coating on hydroxyapatite-coated titanium , 2021, The bone & joint journal.

[11]  X. Ning,et al.  Antibacterial and antibiofilm properties of graphene and its derivatives. , 2021, Colloids and surfaces. B, Biointerfaces.

[12]  P. Show,et al.  Antibiotics: An overview on the environmental occurrence, toxicity, degradation, and removal methods , 2021, Bioengineered.

[13]  Khaled S. Allemailem,et al.  The prospects of antimicrobial coated medical implants , 2021, Journal of applied biomaterials & functional materials.

[14]  Mayra Eliana Valencia Zapata,et al.  The Role of Chitosan and Graphene Oxide in Bioactive and Antibacterial Properties of Acrylic Bone Cements , 2020, Biomolecules.

[15]  M. Mattarelli,et al.  Bio-mechanical characterization of a CAD/CAM PMMA resin for digital removable prostheses. , 2020, Dental materials : official publication of the Academy of Dental Materials.

[16]  G. Cabrera-Barjas,et al.  Sustained Release of Linezolid from Prepared Hydrogels with Polyvinyl Alcohol and Aliphatic Dicarboxylic Acids of Variable Chain Lengths , 2020, Pharmaceutics.

[17]  J. Esteban,et al.  Electrochemical characterization of coatings for local prevention of Candida infections on titanium-based biomaterials , 2020, Progress in Organic Coatings.

[18]  S. Gangloff,et al.  Antibiotic Tolerance of Staphylococcus aureus Biofilm in Periprosthetic Joint Infections and Antibiofilm Strategies , 2020, Antibiotics.

[19]  S. Vijayakumar,et al.  Supramolecular hydrogels based on cellulose for sustained release of therapeutic substances with antimicrobial and wound healing properties. , 2020, Carbohydrate polymers.

[20]  J. Esteban,et al.  A Biodegradable Antifungal-Loaded Sol–Gel Coating for the Prevention and Local Treatment of Yeast Prosthetic-Joint Infections , 2020, Materials.

[21]  J. Esteban,et al.  A New Antibiotic-Loaded Sol-Gel can Prevent Bacterial Intravenous Catheter-Related Infections , 2020, Materials.

[22]  H. Wong,et al.  Lipid-polymer hybrid nanoparticles carrying linezolid improve treatment of methicillin-resistant Staphylococcus aureus (MRSA) harbored inside bone cells and biofilms. , 2020, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[23]  Yirong Zeng,et al.  Garlic extract in prosthesis-related infections: a literature review , 2020, The Journal of international medical research.

[24]  F. Alseroury,et al.  Photocatalytic degradation of cefoxitin sodium antibiotic using novel BN/CdAl2O4 composite , 2020 .

[25]  F. Mulero,et al.  A New Antibiotic-Loaded Sol-Gel Can Prevent Bacterial Prosthetic Joint Infection: From in vitro Studies to an in vivo Model , 2020, Frontiers in Microbiology.

[26]  Tugba Eren Boncu,et al.  In vitro and in vivo evaluation of linezolid loaded electrospun PLGA and PLGA/PCL fiber mats for prophylaxis and treatment of MRSA induced prosthetic infections. , 2020, International journal of pharmaceutics.

[27]  B. Raymond,et al.  Biofilms facilitate cheating and social exploitation of β-lactam resistance in Escherichia coli , 2019, npj Biofilms and Microbiomes.

[28]  C. Aparicio,et al.  Nano-scale modification of titanium implant surfaces to enhance osseointegration. , 2019, Acta biomaterialia.

[29]  J. Esteban,et al.  Functionalization of sol-gel coatings with organophosphorus compounds for prosthetic devices. , 2019, Colloids and surfaces. B, Biointerfaces.

[30]  E. Burd,et al.  Antibiotic combinations that exploit heteroresistance to multiple drugs effectively control infection , 2019, Nature Microbiology.

[31]  A. Gorle,et al.  Development and validation of Spectrophotometry methods for estimation of linezolid in bulk and in pharmaceutical Dosage formulation , 2019, Journal of Drug Delivery and Therapeutics.

[32]  Á. Soriano,et al.  The Different Microbial Etiology of Prosthetic Joint Infections according to Route of Acquisition and Time after Prosthesis Implantation, Including the Role of Multidrug-Resistant Organisms , 2019, Journal of clinical medicine.

[33]  H. Mao,et al.  In Vivo Bioluminescence Imaging in a Rabbit Model of Orthopaedic Implant-Associated Infection to Monitor Efficacy of an Antibiotic-Releasing Coating , 2019, The Journal of bone and joint surgery. American volume.

[34]  Robin Patel,et al.  Microbiology of polymicrobial prosthetic joint infection. , 2019, Diagnostic microbiology and infectious disease.

[35]  Xiaowei Yu,et al.  Coatings as the useful drug delivery system for the prevention of implant-related infections , 2018, Journal of Orthopaedic Surgery and Research.

[36]  Daniel J. Wilson,et al.  The distribution of bacterial doubling times in the wild , 2017, bioRxiv.

[37]  B. Sunderland,et al.  Evaluation of the stability of linezolid in aqueous solution and commonly used intravenous fluids , 2017, Drug design, development and therapy.

[38]  A. Benditz,et al.  Efficacy of antibiotic treatment of implant-associated Staphylococcus aureus infections with moxifloxacin, flucloxacillin, rifampin, and combination therapy: an animal study , 2017, Drug design, development and therapy.

[39]  W. Zimmerli,et al.  The use of rifampin in staphylococcal orthopaedic-device-related infections. , 2017, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[40]  C. García-García,et al.  Evaluation of the role of surface pretreatments on the corrosion process. Correlation between conventional and electrochemical tests , 2017 .

[41]  M. Gurruchaga,et al.  Control of the degradation of silica sol-gel hybrid coatings for metal implants prepared by the triple combination of alkoxysilanes , 2016 .

[42]  Á. Soriano,et al.  Time trends in the aetiology of prosthetic joint infections: a multicentre cohort study. , 2016, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[43]  Bao-sheng Liu,et al.  Investigation on the effect of fluorescence quenching of bovine serum albumin by cefoxitin sodium using fluorescence spectroscopy and synchronous fluorescence spectroscopy. , 2016, Luminescence : the journal of biological and chemical luminescence.

[44]  Jonathan C. Knowles,et al.  Sol-gel based materials for biomedical applications , 2016 .

[45]  R. B. Figueira,et al.  Hybrid sol-gel coatings: Smart and green materials for corrosion mitigation , 2016 .

[46]  Martin Müller,et al.  Testing of antibiotic releasing implant coatings to fight bacteria in combat-associated osteomyelitis – an in-vitro study , 2016, International Orthopaedics.

[47]  S. Radin,et al.  Percutaneous external fixator pins with bactericidal micron-thin sol-gel films for the prevention of pin tract infection. , 2015, Biomaterials.

[48]  B. Brooks,et al.  Therapeutic strategies to combat antibiotic resistance. , 2014, Advanced drug delivery reviews.

[49]  S. Radin,et al.  Bactericidal micron-thin sol-gel films prevent pin tract and periprosthetic infection. , 2014, Military medicine.

[50]  Calin S. Moucha,et al.  Antibacterial Surface Treatment for Orthopaedic Implants , 2014, International journal of molecular sciences.

[51]  P. Ducheyne,et al.  Sol-gel silica controlled release thin films for the inhibition of methicillin-resistant Staphylococcus aureus. , 2014, Biomaterials.

[52]  D. Missiakas,et al.  Growth and laboratory maintenance of Staphylococcus aureus. , 2013, Current protocols in microbiology.

[53]  W. Zimmerli,et al.  Antimicrobial treatment concepts for orthopaedic device-related infection. , 2012, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[54]  Evangelos J. Giamarellos-Bourboulis,et al.  Carrier Systems for the Local Delivery of Antibiotics in Bone Infections , 2000, Drugs.

[55]  F. K. Gould,et al.  Prosthetic joint infections: single versus combination therapy. , 2010, The Journal of antimicrobial chemotherapy.

[56]  S. Radin,et al.  Controlled release of vancomycin from thin sol‐gel films on implant surfaces successfully controls osteomyelitis , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[57]  J. Bumgardner,et al.  Chitosan Films: A Potential Local Drug Delivery System for Antibiotics , 2008, Clinical orthopaedics and related research.

[58]  E. Gómez-Barrena,et al.  Evaluation of Quantitative Analysis of Cultures from Sonicated Retrieved Orthopedic Implants in Diagnosis of Orthopedic Infection , 2007, Journal of Clinical Microbiology.

[59]  J. Pagés,et al.  Intracellular accumulation of linezolid in Escherichia coli, Citrobacter freundii and Enterobacter aerogenes: role of enhanced efflux pump activity and inactivation. , 2007, The Journal of antimicrobial chemotherapy.

[60]  S. Radin,et al.  Controlled release of vancomycin from thin sol-gel films on titanium alloy fracture plate material. , 2007, Biomaterials.

[61]  S. Aaron,et al.  Multiple Combination Bactericidal Testing of Staphylococcal Biofilms from Implant-Associated Infections , 2006, Antimicrobial Agents and Chemotherapy.

[62]  L. Jianguo,et al.  EIS study of corrosion behaviour of organic coating/Dacromet composite systems , 2005 .

[63]  J. Costerton,et al.  Can laboratory reference strains mirror "real-world" pathogenesis? , 2005, Trends in microbiology.

[64]  Kwangsok Kim,et al.  Incorporation and controlled release of a hydrophilic antibiotic using poly(lactide-co-glycolide)-based electrospun nanofibrous scaffolds. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[65]  A. MacGowan,et al.  Antibiotic treatment of gram-positive bone and joint infections. , 2004, The Journal of antimicrobial chemotherapy.

[66]  M. Hamilton,et al.  How to optimize the drop plate method for enumerating bacteria. , 2001, Journal of microbiological methods.

[67]  E. Bouza,et al.  Monotherapy versus combination therapy for bacterial infections. , 2000, The Medical clinics of North America.

[68]  H. C. van der Mei,et al.  Initial adhesion and surface growth of Staphylococcus epidermidis and Pseudomonas aeruginosa on biomedical polymers. , 2000, Journal of biomedical materials research.

[69]  R. H. Robins,et al.  Susceptibility of morpholine substituents to photo‐oxidative decomposition‐identification of photo‐oxidative degradants of linezolid (PNU‐100766) , 1999 .

[70]  H. Okamura,et al.  [Clinical experience with cefoxitin used for the prevention of postoperative infections]. , 1982, The Japanese Journal of Antibiotics.

[71]  J. Campos,et al.  Chemoprophylaxis with cefoxitin and cephalothin in orthopedic surgery: a comparison , 1981, Antimicrobial Agents and Chemotherapy.

[72]  M. Dillingham,et al.  Clinical evaluation of cefoxitin in treatment of infections in 47 orthopedic patients. , 1979, Reviews of Infectious Diseases.

[73]  R. Perkins Surgical considerations in skin and soft-tissue infections and osteomyelitis treated with cefoxitin sodium. , 1978, Journal of Antimicrobial Chemotherapy.

[74]  J. Hou,et al.  -lactam antibiotics: their physicochemical properties and biological activities in relation to structure. , 1971, Journal of Pharmacy and Science.