Antimicrobial Distribution From Local Delivery Depends on Dose

Abstract

Tissue distribution after local delivery has been quantified over a period of 5 hours on 7-T MRI in a rabbit model using gadolinium-labeled diethylenetriamine pentaacetic acid (Gd-DTPA) as an antimicrobial surrogate; however, it is unknown how the Gd-DTPA load in a local depot will affect the duration of high-concentration Gd-DTPA in local tissues after surgical débridement. We determined whether the Gd-DTPA load in bone cement affected its local tissue distribution over a period of 1 month after local delivery. A 1-cm3 soft tissue dead space was created in the quadriceps of seven rabbits and filled with gadolinium-loaded bone cement. At 7, 14, and 33 days, the volume of tissue with a Gd-DTPA concentration of more than 14 μg/mL was calculated from T1-weighted images using 7-T MRI. Differences in volumes of distribution were analyzed with ANOVA. The volume of tissue with more than 14 μg/mL Gd-DTPA was much larger from higher gadolinium loads on Day 7 (p=0.02) (2121 mm3 for 10 g and 665 mm3 for 1 g) and smaller with time for the 10-g formulation (2121 mm3 on Day 7 and 1241 mm3 on Day 14). Volume of distribution and duration of Gd-DTPA after local delivery increased with increasing load in the cement and decreased with time. For local delivery, high antimicrobial concentrations would be expected in greater volumes of tissue, for longer durations, when higher antimicrobial loads are used.