Aims. Calcium sulphate (CaSO. 4. ) is a resorbable material that can be used simultaneously as filler of a dead space and as a carrier for the local application of antibiotics. Our aim was to describe the systemic exposure and the wound fluid concentrations of vancomycin in patients treated with vancomycin-loaded CaSO. 4. as an adjunct to the routine therapy of bone and joint infections. Patients and Methods. A total of 680 post-operative blood and 233 wound fluid samples were available for analysis from 94 implantations performed in 87 patients for various infective indications. Up to 6 g of vancomycin were used. Non-compartmental pharmacokinetic analysis was performed on the data from 37 patients treated for an infection of the hip. Results. The overall systemic exposure remained within a safe range, even in patients with post-operative renal failure, none requiring removal of the pellets. Local concentrations were approximately ten times higher than with polymethylmethacrylate (PMMA) as a carrier, but remained below reported cell toxicity thresholds. Decreasing concentrations in wound fluid were observed over several weeks, but remained above the common minimum inhibitory concentrations for Staphylococcus up to three months post-operatively. . Conclusion. This study provides the first pharmacokinetic description of the local application of vancomycin with CaSO. 4. as a carrier, documenting slow release, systemic safety and a release profile far more interesting than from PMMA. In particular, considering in vitro data, concentrations of vancomycin active against staphylococcal biofilm were seen for several weeks. Cite this article: Bone Joint J 2017;99-B:1537–44

Aim. Determine the time concentration profile required to achieve vancomycin-mediated eradication of Staphylococcus aureus biofilm. This is critical for the identification of performance targets for local antibiotic delivery, yet has not been described. Method. Mature S. aureus UAMS-1 biofilms were grown on titanium-aluminum-niobium discs in Mueller Hinton broth (MHB). After 7 days, the discs were incubated in MHB containing vancomycin at 100, 200, 500, 1′000 and 2′000 mg/L. Both static and shaking conditions were tested. Samples were retrieved at intervals for up to 28 days for quantification of residual biofilm by sonication and serial dilution plating. One additional disc was processed per time point for scanning electron microscopy. Results. Progressive and significant reduction of viable bacteria was observed over time at all vancomycin concentrations in both static and shaking conditions. After 28 days under static conditions, the S. aureus biofilm was completely eradicated at 200 mg/L vancomycin and higher concentrations. Biofilm could could however not be eradicated under shaking conditions at any concentration. Logistic regression documents time of exposure at ≥200 mg/L as being the essential determinant of eradication. Conclusions. The clinical relevance of the present study is that it is not impossible to eradicate mature S. aureus biofilm from metal implants by vancomycin alone, fostering efforts to optimize local delivery. The required time concentration profile cannot be achieved yet by systemic administration or any of the local delivery vehicles available. Even longer exposure as 28 days might be required as wound fluid flow might influence unfavourably biofilm resistance to vancomycin

We present the first systematic review conducted by the UK Defence Medical Services in conjunction with the Cochrane Collaboration. Irrigation fluids are used to remove contamination during the surgical treatment of traumatic wounds in order to prevent infection. This review aims to determine whether there is evidence that one wound irrigation fluid is superior to another at reducing infection. A pre-published methodology was used and two reviewers independently assessed the search results. The search produced 917 studies, of which three met the inclusion criteria. All were studies in open fractures, incorporating a total of 2,903 patients. Each RCT involved a distinct comparison, precluding meta-analysis: i) sterile saline vs. distilled/boiled water; ii) antibiotic solution vs. soap solution; iii) saline vs. soap solution. The odds ratios of infection following irrigation with various fluids was as follows: i) saline vs. distilled or boiled water 0.25 (95%CI 0.08–0.73); ii) antibiotic solution vs. soap 1.42 (95%CI 0.82–2.46); iii) saline vs. soap solution 1.00 (95%CI 0.80–1.26). These results suggest that neither soap nor antibiotic solution is superior to saline and that saline is inferior to distilled or boiled water