Article Figures & Data
Figures
- FIG 1
Characterization of PUR and diflunisal-loaded PUR. SEM images of PUR foams containing 0 (A), 10 (B), and 20 mM (C) diflunisal. Scale bar, 200 μm. SEM images of PUR foams were used to determine porosity (%) (D) and pore diameter (μm) (E). (F) Release of diflunisal from PUR. Cumulative release was quantified as the amount of diflunisal released in the leachate normalized by the original amount of diflunisal in the foams. Daily release was quantified as the amount of diflunisal in the leachate at each time point. Error bars represent standard deviation (SD). n = 6 per group.
- FIG 2
Diflunisal does not inhibit vancomycin activity against S. aureus in vitro. S. aureus was cultured overnight with (A) or without (B) 25 μg/ml diflunisal. Diflunisal concentration was based on the total amount of diflunisal released from the foams as determined in Fig. 1. Vancomycin was delivered at concentrations near the MIC with and without diflunisal to characterize the effect of combined delivery on the bactericidal capability of vancomycin. n = 3 technical replicates per group. Error bars represent SD. Data are representative of 3 independent trials. Significance determined by Student's t test.
- FIG 3
Local diflunisal therapy does not inhibit systemic vancomycin activity in vivo. (A) Vancomycin was delivered at 4 different concentrations to determine a suboptimal dose that would significantly decrease the bacterial burdens in murine femurs infected with S. aureus (n = 5 mice per group). Horizontal lines represent the mean. Error bars represent SD. Dotted line depicts the limit of detection (LOD) for bacterial burdens. *, P < 0.05; ****, P < 0.0001. (B, C) Mice were treated with either PUR+Veh or PUR+Dif (see Table 1). At 14 days postinfection, femurs (B) and foams (C) were harvested for CFU enumeration. n = 4 or 5 mice per group (one mouse in the PUR+Veh group had to be euthanized according to humane endpoints). Control group demonstrates bacterial burdens consistent with separate trials (data not shown). *, P < 0.05 relative to PUR+Veh treatment as determined by Student's t test.
- FIG 4
Coadministration of local diflunisal treatment and systemic vancomycin therapy during osteomyelitis. (A) Micro-CT reconstructions of femurs treated with PUR+Veh, PUR+Dif+Veh, PUR+Vanc, or PUR+Dif+Vanc (see Table 1). n = 5 mice per group. One control group mouse suffered pathological fracture (second from left in the PUR+Veh group). (B) Quantification of cortical bone destruction. Error bar represents SD. **, P < 0.01; ***, P < 0.001 as determined by Student's t test.
Tables
- TABLE 1
Groups and doses of mice treated with vancomycin and diflunisal
Supplemental material
- Supplemental file 1 -
Supplemental Figures S1 to S3
PDF, 219K
- Supplemental file 1 -
