Sutures can cause challenging surgical site infections, due to capillary effects resulting in bacteria permeating wounds. Anti-microbial sutures may avoid these complications by inhibiting bacterial pathogens. Recently, first triclosan-resistances were reported and therefore alternative substances are becoming clinically relevant. As triclosan alternative chlorhexidine, the “gold standard” in oral antiseptics was used. The aim of the study was to optimize novel slow release chlorhexidine coatings based on fatty acids in surgical sutures, to reach a high anti-microbial efficacy and simultaneously high biocompatibility. Sutures were coated with chlorhexidine laurate and chlorhexidine palmitate solutions leading to 11, 22 or 33 µg/cm drug concentration per length. Drug release profiles were determined in aqueous elutions. Antibacterial efficacy against Staphylococcus aureus was assessed in agar diffusion tests. Biocompatibility was evaluated via established cytotoxicity assay (WST-1). A commercially triclosan-containing suture (Vicryl Plus), was used as anti-microbial reference. All coated sutures fulfilled European Pharmacopoeia required tensile strength and proved continuous slow drug release over 96 hours without complete wash out of the coated drug. High anti-microbial efficacy for up to 5 days was observed. Regarding biocompatibility, sutures using 11 µg/cm drug content displayed acceptable cytotoxic levels according to ISO 10993-5. The highest potential for human application were shown by the 11 µg/cm chlorhexidine coated sutures with palmitic acid. These novel coated sutures might be alternatives to already established anti-microbial sutures such as Vicryl Plus in case of triclosan-resistance. Chlorhexidine is already an established oral antiseptic, safety and efficacy should be proven for clinical applications in anti-microbial sutures.

Implantable devices are highly susceptible to infection and are therefore a major risk in surgery. The present work presents a novel strategy to prevent the formation of a biofilm on polytetrafluoroethylene (PTFE) grafts. PTFE grafts were coated with gentamicin and teicoplanin incorporated into different lipid-like carriers under aseptic conditions in a dipping process. Poly- d , l -lactic acid, tocopherol acetate, the diglyceride Softisan 649, and the triglyceride Dynasan 118 were used as drug carriers. The drug release kinetics, anti-infective characteristics, biocompatibility, and hemocompatibility of the coatings developed were studied. All coatings showed an initial drug burst, followed by a low continuous drug release over 96 h. The dimension of release kinetics depended on the carrier used. All coated prostheses reduced bacterial growth drastically over 24 h, even below pathologically relevant concentrations. Different cytotoxic levels could be observed, revealing tocopherol acetate as the most promising biocompatible carrier. A possible reason for the highly cytotoxic effect of Softisan 649 could be assessed by demonstrating incorporated lipids in the cell soma with Oil Red O staining. Tromboelastography studies, enzyme-linked immunosorbent assays, and an amidolytic substrate assay could confirm the hemocompatibility of individual coatings. The development of the biodegradable drug delivery systems described here and in vitro studies of those systems highlight the most important requirements for effective as well as compatible anti-infective coatings of PTFE grafts. Through continuous local release, high drug levels can be produced at only the targeted area and physiological bacterial proliferation can be completely inhibited, while biocompatibility as well as hemocompatibility can be ensured.

The implant-bone interface is the scene of competition between microorganisms and distinct types of tissue cells. In the past, various strategies have been followed to support bony integration and to prevent bacterial implant-associated infections. In the present study we investigated the biological properties of diamond-like carbon (DLC) surfaces containing silver nanoparticles. DLC is a promising material for the modification of medical implants providing high mechanical and chemical stability and a high degree of biocompatibility. DLC surface modifications with varying silver concentrations were generated on medical-grade titanium discs, using plasma immersion ion implantation-induced densification of silver nanoparticle-containing polyvinylpyrrolidone polymer solutions. Immersion of implants in aqueous liquids resulted in a rapid silver release reducing the growth of surface-bound and planktonicStaphylococcus aureusandStaphylococcus epidermidis. Due to the fast and transient release of silver ions from the modified implants, the surfaces became biocompatible, ensuring growth of mammalian cells. Human endothelial cells retained their cellular differentiation as indicated by the intracellular formation of Weibel-Palade bodies and a high responsiveness towards histamine. Our findings indicate that the integration of silver nanoparticles into DLC prevents bacterial colonization due to a fast initial release of silver ions, facilitating the growth of silver susceptible mammalian cells subsequently.

Acute cholangitis is a life-threatening bacterial infection of the biliary tract. Main focus of this study was to create a useful risk prediction model that helps physicians to assign patients with acute cholangitis into different management groups. 981 cholangitis episodes from 810 patients were analysed retrospectively at a German tertiary center. Out of eleven investigated statistical models fit to 22 predictors, the Random Forest model achieved the best (cross-)validated performance to predict mortality. The receiver operating characteristics (ROC) curve revealed a mean area under the curve (AUC) of 91.5 %. Dependent on the calculated mortality risk, we propose to stratify patients with acute cholangitis into a high and low risk group. The mean sensitivity, specificity, positive and negative predictive value of the corresponding optimal cutpoint were 82.9 %, 85.1 %, 19.0 % and 99.3 %, respectively. All of these results emerge from nested (cross-)validation and are supposed to reflect the model’s performance expected for external data. An implementation of our risk prediction model including the specific treatment recommendations adopted from the Tokyo guidelines is available on http://www2.imse.med.tum.de:3838/ . Our risk prediction model for mortality appears promising to stratify patients with acute cholangitis into different management groups. Additional validation of its performance should be provided by further prospective trails.