Quantification of cefuroxime and flucloxacillin in synovial tissue and bone using ultra-performance convergence chromatography-tandem mass spectrometry.

After a revision surgery, approximately 1-2 % of patients will develop a periprosthetic joint infection (PJI). During the revision surgery, the infected prosthesis is removed, a debridement is performed and a new or temporary spacer is placed. Additionally, patients are treated with antibiotics during and after the surgery. Adequate exposure of the administered antibiotic to the pathogen is of crucial importance during the treatment of any infection. Inadequately low concentrations are associated with an increase in antibiotic resistance, antibiotic related side effects, treatment failures and prolonged infections. While high concentrations may lead to serious adverse events and potential lasting damage. Despite the importance of optimal dosing, there is a lack of knowledge with respect to the correlation between the plasma concentrations and target site concentrations of the antibiotics. Two of the commonly administered antimicrobial agents during the arthroplasty exchange are cefuroxime and flucloxacillin. Therefore, an accurate, specific, and sensitive quantification method is required in order to assess pharmacokinetics of cefuroxime and flucloxacillin in synovial tissue and bone. The aim of this study is to develop and validate a quantification method for the measurement of cefuroxime and flucloxacillin in human synovial tissue and bone using the UPC2-MS/MS conform Food and Drug Administration guidelines. The method was found linear for both compounds in both matrices (r2 > 0.990) from 1 µg/g to 20 µg/g, except for cefuroxime in bone, which was validated from 1 µg/g to 15 µg/g. We developed and validated a quantification method for cefuroxime and flucloxacillin in synovial tissue and bone using a simple sample preparation and a short analysis run time of 5.0 min, which has been already successfully applied in a clinical study. To our knowledge, no methods have been described earlier for the simultaneous quantification of cefuroxime and flucloxacillin in synovial tissue and bone.

Quantification of vancomycin and clindamycin in human plasma and synovial fluid applying ultra-performance liquid chromatography tandem mass spectrometry.

Periprosthetic joint infection is a challenging infection involving the joint prosthesis and adjacent tissue, such as synovial fluid, synovial tissue, and bone tissue. The current treatment consists of multiple surgical revisions and long-term antibiotic therapy. Treatment failure can cause poor functional outcome and reduced quality of life. Further research on the extent of antibiotic penetration into the infected tissues is of great importance. Our work aimed to develop and validate a novel ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of the commonly administered antibiotics vancomycin and clindamycin in plasma and synovial fluid. An extraction procedure consisting of zinc sulfate precipitation and dilution with eluent was used for both analytes. Chromatographic separation was performed on a Waters Acquity UPLC HSS T3 C18 column (1.8 µm, 2.1 × 100 mm), and quantification was carried out by a Waters Xevo TQ-S micro mass spectrometer. Stable isotope-labeled vancomycin-d10 served as internal standard. The method validation was performed based on the guidelines of the EMA and FDA. The calibration curves were linear over the range of 0.5-50 mg/L, with a coefficient of determination above 0.990. The validation results for precision and accuracy, specificity, matrix effects and stability were all within the acceptance range. An accurate and rapid method for the simultaneous quantification of vancomycin and clindamycin in human plasma and synovial fluid on the UPLC-MS/MS was developed, optimized and validated. The analysis has a run time of 5.2 min and 50 µL sample volume is needed. This developed method was successfully applied in eight patients with PJI and is suitable to determine the exposure of antibiotics in plasma and synovial fluid in patients during current PK/PD studies.

The influence of preoperative psychological distress on pain and function after total knee arthroplasty: a systematic review and meta-analysis.

AIMS: We performed a meta-analysis investigating the association between preoperative psychological distress and postoperative pain and function after total knee arthroplasty (TKA). MATERIALS AND METHODS: Pubmed/Medline, Embase, PsycINFO, and the Cochrane library were searched for studies on the influence of preoperative psychological distress on postoperative pain and physical function after TKA. Two blinded reviewers screened for eligibility and assessed the risk of bias and the quality of evidence. We used random effects models to pool data for the meta-analysis. RESULTS: Six prospective cohort studies, with a total of 1525 patients, were included. The random effects models showed significantly poorer outcomes in patients who preoperatively had elevated scores on the pain catastrophizing scale, worse 36-Item Short-Form Health Survey (SF-36) mental health score, symptoms of anxiety and/or depression, and somatization dysfunction. After 12 months, the standard mean difference for pain was -0.74 (95% confidence interval (CI) -1.04 to -0.44) and -0.56 (95% CI -0.80 to -0.32) for function. CONCLUSION: Preoperative pain catastrophizing, mental distress, symptoms of anxiety and/or depression, and somatoform disorders appear to adversely affect pain and function after TKA. Some patients undergoing TKA may therefore need psychological support to improve the outcome and quality of life.