Distribution of locally delivered antimicrobials is limited by cortical bone: a pilot study

Local delivery is required to achieve the high antimicrobial concentrations needed to treat biofilm-forming infections. The delivery site is commonly either in the intramedullary canal or at the periosteal surface. It is unknown whether locally delivered antimicrobials are transported transcortically between the endosteal and periosteal surfaces when the infection involves the opposite surface.

(1) Are antimicrobials transported transcortically between the endosteal and periosteal surfaces over time? And (2) are transcortical antimicrobials transported uniformly over the cortical surface?

To study transcortical antimicrobial transport, 12 human cadaveric femoral segments obtained from two women aged 63 and 64 years and one man aged 64 years were filled with antimicrobials. Three diaphyseal segments were filled with 5 wt% vancomycin in an N-isopropylacrylamide-based hydrogel and eluted in phosphate-buffered saline under infinite-sink conditions for 5 days; vancomycin was assayed by high-performance liquid chromatography. Nine segments (three infraisthmal diaphysis, three metaphysis, three epiphysis) embedded in 0.1% agarose gel were filled with aqueous doxycycline (400 μg/mL) and imaged under ultraviolet light for fluorescence on the periosteal surface at 15-minute intervals for 3 days.

Transcortical vancomycin elution occurred: 8.65 mg during Day 1 and 26.5 mg by Day 5. Fluorescence from transcortical doxycycline transport was only visualized at focal locations corresponding to vascular foramina, appearing first at 5 to 10 minutes, with none over the majority of the periosteal surface for up to 24 hours.

Transcortical transport of locally delivered antimicrobials occurs primarily through vascular foramina.

Transcortical antimicrobial transported may not be adequate to achieve therapeutic levels for infection on the far side of an intact cortex.