Glutathione-Responsive Multifunctional Nanoparticles Based on Mannose-Modified Pillar[5]arene for Targeted Antibiotic Delivery against Intracellular Methicillin-Resistant S. aureus

MRSA can evade the immune system once they are engulfed by phagocytic host cells. This protects them against the bactericidal action of antibiotics and allows the infection to remain latent...

Controlled and Local Delivery of Antibiotics by 3D Core/Shell Printed Hydrogel Scaffolds to Treat Soft Tissue Infections

Soft tissue infections in open fractures or burns are major cause for high morbidity in trauma patients. Sustained, long-term and localized delivery of antimicrobial agents is needed for early eradication of these infections. Traditional (topical or systemic) antibiotic delivery methods are associated with a variety of problems, including their long-term unavailability and possible low local concentration. Novel approaches for antibiotic delivery via wound coverage/healing scaffolds are constantly being developed. Many of these approaches are associated with burst release and thus seldom maintain long-term inhibitory concentrations. Using 3D core/shell extrusion printing, scaffolds consisting of antibiotic depot (in the core composed of low concentrated biomaterial ink 3% alginate) surrounded by a denser biomaterial ink (shell) were fabricated. Denser biomaterial ink (composed of alginate and methylcellulose or alginate, methylcellulose and Laponite) retained scaffold shape and modulated antibiotic release kinetics. Release of antibiotics was observed over seven days, indicating sustained release characteristics and maintenance of potency. Inclusion of Laponite in shell, significantly reduced burst release of antibiotics. Additionally, the effect of shell thickness on release kinetics was demonstrated. Amalgamation of such a modular delivery system with other biofabrication methods could potentially open new strategies to simultaneously treat soft tissue infections and aid wound regeneration.

Local Antibiotic Delivery Systems in Diabetic Foot Osteomyelitis: A Brief Review

Diabetic foot osteomyelitis (DFO) is a severe, difficult to treat infection. Local antibiotic delivery has been studied as a potential therapeutic adjunct following surgery for DFO. This review aims to summarize the evidence on local antibiotic delivery systems in DFO. PubMed database was searched up to March 2020. Overall, 16 studies were identified and included: 3 randomized controlled trials (RCTs), 3 retrospective studies (RSs), and 10 case series. In the RCTs, gentamicin-impregnated collagen sponges significantly improved clinical healing rates and slightly improved duration of hospitalization. In the RSs, antibiotic-impregnated calcium sulfate beads non-significantly improved all healing parameters, but did not reduce post-operative amputation rates or time of healing. The majority of case series used calcium sulfate beads, achieving adequate rates of healing and eradication of infection. In conclusion, evidence for add-on local antibiotic delivery in DFO is still limited; more data are needed to assess this therapeutic measure.

Antibiotic selection and risk profiles in patients receiving antibacterial cardiovascular implantable electronic device envelopes – a real world sample and analysis

Background The use of a cardiovascular implantable electronic device (CIED) envelope impregnated with antibiotics provides short-term local antibiotic delivery in the implant pocket and may lower infection risk. Biologic antibacterial (BIO) envelopes, such as the porcine extracellular matrix (ECM) device hydrated with antibiotics, facilitate active remodeling of the pocket into vital, vascularized tissue and provide short-term local antibiotic delivery. Limited clinical data is available on real-world clinician patient selection criteria, antibiotic choices, or clinical outcomes. Purpose To explore antibiotic hydration solution physician choices with respect to patient profiles, and to determine post-implant infection outcomes in patients receiving a CIED BIO envelope. Methods A post-hoc sub-analysis of a multicenter, non-randomized study of 1017 patients receiving a biologic envelope (hydrated with or without antibiotics) during CIED procedures (SECURE Study) assessed antibiotic hydration choices, patient risk profiles, and the type and timing of infection for days 0–90 post procedure. Patient selection and antibiotic hydration choice were at the discretion of the treating physician. Results 850 patients received BIO envelopes, with a mean age of 71.9 years, and 60.5% having ≥2 standard infection risk factors. High power devices accounted for 47.6% and reoperations for 44.0% of the procedures. Antibiotic choice for envelope hydration prior to implantation is described in Table 1 below. Also, antibiotic combinations with gentamicin were used in 18.1% and other antibiotic combinations in 9.2% of patients. Patients receiving gentamicin hydrated BIO envelopes (BIO+G) trended toward fewer pocket infections vs. those without gentamicin (BIO-G) (0.0% vs. 1.6%, p=0.070) but the overall pocket infection rate of 1.2% was not significantly different based upon antibiotic choice. In a multivariate logistic regression model designed to predict the total infection rate, the use of gentamicin was associated with a 3-fold reduction in likelihood of infection, OR 3.0 (1.0–10.0); AUC=0.70. No differences in overall infection rates among patients undergoing lead or pocket revision only procedures (0.0% vs. 0.0%) or other major adverse events were observed based upon antibiotic usage. Conclusions Real world clinical decision-making regarding antibiotic choice for biologic antibacterial envelopes varies among implanting clinicians and influences observed outcomes. The use of biologic antibacterial envelopes hydrated with gentamicin was associated with a lower likelihood of infection within 90 days when compared to biologic envelopes hydrated without gentamicin. Clinical trials to optimize patient selection processes and determine the best antibiotic choice when employing a CIED envelope merit further investigation. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): The work was supported by Aziyo Biologics, Inc. Table 1. BIO Envelope Hydration

Bacterial Outer Membrane Vesicles as Antibiotic Delivery Vehicles

Bacterial outer membrane vesicles (OMVs) are nanometer-scale, spherical vehicles released by Gram-negative bacteria into their surroundings throughout growth. These OMVs have been demonstrated to play key roles in pathogenesis by delivering certain biomolecules to host cells, including toxins and other virulence factors. In addition, this biomolecular delivery function enables OMVs to facilitate intra-bacterial communication processes, such as quorum sensing and horizontal gene transfer. The unique ability of OMVs to deliver large biomolecules across the complex Gram-negative cell envelope has inspired the use of OMVs as antibiotic delivery vehicles to overcome transport limitations. In this review, we describe the advantages, applications, and biotechnological challenges of using OMVs as antibiotic delivery vehicles, studying both natural and engineered antibiotic applications of OMVs. We argue that OMVs hold great promise as antibiotic delivery vehicles, an urgently needed application to combat the growing threat of antibiotic resistance.

Metal and Metal Oxide Nanoparticle as a Novel Antibiotic Carrier for the Direct Delivery of Antibiotics

In addition to the benefits, increasing the constant need for antibiotics has resulted in the development of antibiotic bacterial resistance over time. Antibiotic tolerance mainly evolves in these bacteria through efflux pumps and biofilms. Leading to its modern and profitable uses, emerging nanotechnology is a significant field of research that is considered as the most important scientific breakthrough in recent years. Metal nanoparticles as nanocarriers are currently attracting a lot of interest from scientists, because of their wide range of applications and higher compatibility with bioactive components. As a consequence of their ability to inhibit the growth of bacteria, nanoparticles have been shown to have significant antibacterial, antifungal, antiviral, and antiparasitic efficacy in the battle against antibiotic resistance in microorganisms. As a result, this study covers bacterial tolerance to antibiotics, the antibacterial properties of various metal nanoparticles, their mechanisms, and the use of various metal and metal oxide nanoparticles as novel antibiotic carriers for direct antibiotic delivery.