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.Funding: This research was funded by the Regional Government of Madrid through the program ADITIMAT (ref. P2018/NMT-4411) and CIBERINFEC-CIBER of Infectious Diseases (CB21/13/00043). B.T. would like to thank the Spanish Ministry of Education, Culture, and Sports for the support through the FPU grant (FPU17/05977).Publicad

A biodegradable antifungal-loaded sol-gel coating for the prevention and local treatment of yeast prosthetic-joint infections

Fungal prosthetic-joint infections are rare but devastating complications following arthroplasty. These infections are highly recurrent and expose the patient to the development of candidemia, which has high mortality rates. Patients with this condition are often immunocompromised and present several comorbidities, and thus pose a challenge for diagnosis and treatment. The most frequently isolated organisms in these infections are Candida albicans and Candida parapsilosis, pathogens that initiate the infection by developing a biofilm on the implant surface. In this study, a novel hybrid organo-inorganic sol-gel coating was developed from a mixture of organopolysiloxanes and organophosphite, to which different concentrations of fluconazole or anidulafungin were added. Then, the capacity of these coatings to prevent biofilm formation and treat mature biofilms produced by reference and clinical strains of C. albicans and C. Parapsilosis was evaluated. Anidulafungin-loaded sol-gel coatings were more effective in preventing C. albicans biofilm formation, while fluconazole-loaded sol-gel prevented C. parapsilosis biofilm formation more effectively. Treatment with unloaded sol-gel was sufficient to reduce C. albicans biofilms, and the sol-gels loaded with fluconazole or anidulafungin slightly enhanced this effect. In contrast, unloaded coatings stimulated C. parapsilosis biofilm formation, and loading with fluconazole reduced these biofilms by up to 99%. In conclusion, these coatings represent a novel therapeutic approach with potential clinical use to prevent and treat fungal prosthetic-joint infections.This research was funded by MUTUA MADRILEÑA FOUNDATION, grant number 04078/001 and REGIONAL GOVERNMENT OF MADRID through the ADDIMAT PROGRAM, grant number S2018/NMT-441

A new antibiotic-loaded sol-gel can prevent bacterial intravenous catheter-related infections

The aim of this study was to evaluate the effectiveness of a moxifloxacin-loaded organic-inorganic sol-gel (A50) by locally preventing the catheter-related bloodstream infection (CRBSI) provoked by Staphylococcus epidermidis (S. epidermidis) and the effect resulting from its hydrolytic degradation on coagulation by using a rabbit in-vivo model. A50 coating can completely inhibit growth and would locally prevent CRBSI provoked by S. epidermidis. None of the coagulation blood parameters showed a significant difference constant over time between the control catheter group and the A50-coated catheter group, despite the visible silica release resulting from physiological A50 sol-gel degradation detected in serum at least during the first week. At pathological level, foreign body reaction was present in both of types of catheter, and it was characterized by the presence of macrophages and foreign body giant cell. However, this reaction was different in each group: the A50-coated catheter group showed a higher inflammation with histiocytes, which were forming granuloma-like aggregates with an amorphous crystalline material inside, accompanied by other inflammatory cells such as plasma cells, lymphocytes and mast cells. In conclusion, A50 coating a venous catheter showed excellent bactericidal anti-biofilm response since it completely inhibited S. epidermidis biofilm development and, far from showing procoagulant effects, showed slightly anticoagulant effects.This research received financial support from the Mutua Madrileña Foundation (04078/001). J.J.A.-C. was funded by an FPI grant from the Spanish Ministry of Economics and Competitiveness (BES-2014-069007)

A New Antifungal-Loaded Sol-Gel Can Prevent Candida albicans Prosthetic Joint Infection

This article belongs to the Special Issue Prosthetic Joint Infection: The Challenges of Prevention, Diagnosis and Treatment and Opportunities for Future Research.Fungal PJI is one of the most feared complications after arthroplasty. Although a rare finding, its high associated morbidity and mortality makes it an important object of study. The most frequent species causing fungal PJI is C. albicans. New technology to treat this type of PJI involves organic–inorganic sol-gels loaded with antifungals, as proposed in this study, in which anidulafungin is associated with organophosphates. This study aimed to evaluate the efficacy of an anidulafungin-loaded organic–inorganic sol-gel in preventing prosthetic joint infection (PJI), caused by Candida albicans using an in vivo murine model that evaluates many different variables. Fifty percent (3/6) of mice in the C. albicans-infected, non-coated, chemical-polished (CP)-implant group had positive culture and 100% of the animals in the C. albicans-infected, anidulafungin-loaded, sol-gel coated (CP + A)-implant group had a negative culture (0/6) (p = 0.023). Taking the microbiology and pathology results into account, 54.5% (6/11) of C. albicans-infected CP-implant mice were diagnosed with a PJI, whilst only 9.1% (1/11) of C. albicans-infected CP + A-implant mice were PJI-positive (p = 0.011). No differences were observed between the bone mineral content and bone mineral density of noninfected CP and noninfected CP + A (p = 0.835, and p = 0.181, respectively). No histological or histochemical differences were found in the tissue area occupied by the implant among CP and CP + A. Only 2 of the 6 behavioural variables evaluated exhibited changes during the study: limping and piloerection. In conclusion, the anidulafungin-loaded sol-gel coating showed an excellent antifungal response in vivo and can prevent PJI due to C. albicans in this experimental model.This research received financial support from the Mutua Madrileña Foundation (04078/001)

Influence of Addition of Antibiotics on Chemical and Surface Properties of Sol-Gel Coatings

Infection is one of the most common causes that leads to joint prosthesis failure. In the present work, biodegradable sol-gel coatings were investigated as a promising controlled release of antibiotics for the local prevention of infection in joint prostheses. Accordingly, a sol-gel formulation was designed to be tested as a carrier for 8 different individually loaded antimicrobials. Sols were prepared from a mixture of MAPTMS and TMOS silanes, tris(tri-methylsilyl)phosphite, and the corresponding antimicrobial. In order to study the cross-linking and surface of the coatings, a battery of examinations (Fourier-transform infrared spectroscopy, solid-state 29Si-NMR spectroscopy, thermogravimetric analysis, SEM, EDS, AFM, and water contact angle, thickness, and roughness measurements) were conducted on the formulations loaded with Cefoxitin and Linezolid. A formulation loaded with both antibiotics was also explored. Results showed that the coatings had a microscale roughness attributed to the accumulation of antibiotics and organophosphites in the surface protrusions and that the existence of chemical bonds between antibiotics and the siloxane network was not evidenced