METHODS: Vancomycin at various concentrations was added to JectOS and polymethyl methacrylate (PMMA). Then, the cement was molded into standardized dimensions for in vitro testing. Cylindrical vancomycin-JectOS samples were subjected to compressive strength. The results obtained were compared to PMMA-vancomycin compressive strength data attained from historical controls. The zone of inhibition was carried out using vancomycin-JectOS and vancomycin-PMMA disk on methicillin-resistant strain culture agar.
RESULTS: With the addition of 2.5%, 5%, and 10% vancomycin, the average compressive strengths reduced to 8.01 ± 0.95 MPa (24.6%), 7.52 ± 0.71 MPa (29.2%), and 7.23 ± 1.34 MPa (31.9%). Addition of vancomycin significantly weakened biomechanical properties of JectOS, but there was no significant difference in the compressive strength at increasing concentrations. The average diameters of zone of inhibition for JectOS-vancomycin were 24.7 ± 1.44 (2.5%) mm, 25.9 ± 0.85 mm (5%), and 26.8 ± 1.81 mm (10%), which outperformed PMMA.
CONCLUSION: JectOS has poor mechanical performance but superior elution property. JectOS-vancomycin cement is suitable as a void filler delivering high local concentration of vancomycin. We recommended using it for contained bone defects that do not require mechanical strength.
METHODS: The antimicrobial activity was tested against the planktonic S. aureus cells using the microdilution broth assay, while the antibiofilm activity were evaluated using the crystal violet and resazurin assays. The cytotoxicity of the SBDs was assessed on MRC5 (normal lung tissue), using the MTT assay.
RESULTS: The individual SBDs showed significant reduction of biomass and metabolic activity in both S. aureus strains. Combinations of the SBDs with OXA and VAN were mainly additive against the planktonic cells and cells in the biofilm. Both the compounds showed moderate toxicity against the MRC5 cell line. The selectivity index suggested that the compounds were more cytotoxic to S. aureus than the normal cells.
CONCLUSION: Both the SBD compounds demonstrated promising antimicrobial and antibiofilm activities and have the potential to be further developed as an antimicrobial agent against infections caused by MRSA.
METHODS: A 'meta-model' with 4894 concentrations from 1631 neonates was built using NONMEM, and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming to reach a target AUC0-24 of 400 mg·h/L at steady-state in at least 80% of neonates.
RESULTS: A two-compartment model best fitted the data. Current weight, postmenstrual age (PMA) and serum creatinine were the significant covariates for CL. After model validation, simulations showed that a loading dose (25 mg/kg) and a maintenance dose (15 mg/kg q12h if <35 weeks PMA and 15 mg/kg q8h if ≥35 weeks PMA) achieved the AUC0-24 target earlier than a standard 'Blue Book' dosage regimen in >89% of the treated patients.
CONCLUSIONS: The results of a population meta-analysis of vancomycin data have been used to develop a new dosing regimen for neonatal use and to assist in the design of the model-based, multinational European trial, NeoVanc.