Antibiotic-Polyphosphate Nanocomplexes: A Promising System for Effective Biofilm Eradication

Dennis To,1 Mariana Blanco Massani,1 Débora C Coraça-Huber,2 Anna Seybold,3 Fabrizio Ricci,1,4 Katrin Zöller,1 Andreas Bernkop-Schnürch1 1Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria; 2Research Laboratory for Implant Associated Infections (BIOFILM LAB), Experimental Orthopaedics, University Hospital for Orthopaedics and Traumatology, Medical University Innsbruck, Innsbruck, Austria; 3Department of Zoology, University of Innsbruck, Innsbruck, Austria; 4Thiomatrix Forschungs- und Beratungs GmbH, Innsbruck, AustriaCorrespondence: Andreas Bernkop-Schnürch, Email [email protected]: The eradication of bacterial biofilms poses an enormous challenge owing to the inherently low antibiotic susceptibility of the resident microbiota. The complexation of antibiotics with polyphosphate can substantially improve antimicrobial performance.Methods: Nanoparticular complexes of the model drug colistin and polyphosphate (CP-NPs) were developed and characterized in terms of their particle size and morphology, polydispersity index (PDI), zeta potential, and cytotoxicity. Enzyme-triggered monophosphate and colistin release from the CP-NPs was evaluated in the presence of alkaline phosphatase (AP). Subsequently, antimicrobial efficacy was assessed by inhibition experiments on planktonic cultures, as well as time-kill assays on biofilms formed by the model organism Micrococcus luteus.Results: The CP-NPs exhibited a spherical morphology with particle sizes < 200 nm, PDI < 0.25, and negative zeta potential. They showed reduced cytotoxicity toward two human cell lines and significantly decreased hemotoxicity compared with native colistin. Release experiments with AP verified the enzymatic cleavage of polyphosphate and subsequent release of monophosphate and colistin from CP-NPs. Although CP-NPs were ineffective against planktonic M. luteus cultures, they showed major activity against bacterial biofilms, outperforming native colistin treatment. Strongly elevated AP levels in the biofilm state were identified as a potential key factor for the observed findings.Conclusion: Accordingly, polyphosphate-based nanocomplexes represent a promising tool to tackle bacterial biofilm. Keywords: polyphosphate, colistin, antimicrobial, nanoparticle, nanocomple

The 2023 Orthopedic Research Society's international consensus meeting on musculoskeletal infection: Summary from the in vitro section

AbstractAntimicrobial strategies for musculoskeletal infections are typically first developed with in vitro models. The In Vitro Section of the 2023 Orthopedic Research Society Musculoskeletal Infection international consensus meeting (ICM) probed our state of knowledge of in vitro systems with respect to bacteria and biofilm phenotype, standards, in vitro activity, and the ability to predict in vivo efficacy. A subset of ICM delegates performed systematic reviews on 15 questions and made recommendations and assessment of the level of evidence that were then voted on by 72 ICM delegates. Here, we report recommendations and rationale from the reviews and the results of the internet vote. Only two questions received a ≥90% consensus vote, emphasizing the disparate approaches and lack of established consensus for in vitro modeling and interpretation of results. Comments on knowledge gaps and the need for further research on these critical MSKI questions are included.</jats:p

Use of Lavage Fluids in Arthroplasty to Prevent Postoperative Infections

OBJECTIVE: Lavage techniques are used every day all over the world to clean wounds and surgical approaches. The solutions used vary depending on the application range; there are, for instance, normal saline, antibiotic or antiseptic solutions. This review describes the lavage solutions actually used during arthroplasty and their outcome related to postoperative infections. DATA SOURCES AND EXTRACTION: This is a retrospective review of published articles and books. The information was obtained from online browsers for scientific articles. RESULTS: The lavage fluids used in arthroscopy and those used in experimental studies were normal saline, bacitracin, castile soap, benzalkonium chloride, povidone iodine, Ringer's solution, neomycin sulphate, ethanol, chlorhexidine gluconate, cephalothin sodium, and carbenicillin indanyl sodium. CONCLUSIONS: As few clinical studies were carried out with lavage solutions, most of the results are based on experimental studies. A "golden standard" is still missing

Material modifications enhancing the antibacterial properties of two biodegradable poly(3-hydroxybutyrate) implants

Abstract The aim of this study was to evaluate the antimicrobial efficacy of adding a gentamicin palmitate (GP) coating and zirconium dioxide (ZrO2) to biodegradable poly(3-hydroxybutyrate) (PHB) to reduce biofilm formation. Cylindrical pins with and without a coating were incubated in Müller-Hinton broth inoculated with 2 × 105 colony-forming units (CFU) ml-1 of Staphylococcus aureus for 2 d or 7 d, then sonicated to disrupt biofilms. Pure PHB (PHB + GP) and PHB pins with ZrO2 added (PHBzr + GP) were coated with GP and compared with PHB pins lacking a coating (PHB). Cells (CFU) were counted to quantify the number of bacteria in the biofilm and a cell proliferation assay was employed to evaluate metabolic activity, and scanning electron microscopy (SEM) was performed to visualize the structure of the biofilm. After 2 d of incubation there were significantly more cells in biofilms on PHB pins than PHB + GP and PHBzr + GP pins (p &lt; 0.0001), and cells in the sonication fluid obtained from GP-coated pins exhibited significantly lower metabolic activity than cells from uncoated PHB pins (p &lt; 0.0001). After 7 d of incubation metabolic activity was lowest for PHBzr + GP, with significant differences between PHB and PHBzr + GP (p = 0.001). SEM revealed more cells attached to the surface, and more structured biofilms, on pins without a coating. Coating pins with GP significantly reduced early biofilm formation on PHB implants. This could lower the potential risk of surgical site infections when using PHB implants. Addition of ZrO2 might further enhance the antibacterial properties. Such modification of the implant material should therefore be considered when developing new biodegradable PHB implants.</jats:p