Date: 08 Feb 2014

Antimicrobial Distribution From Local Delivery Depends on Dose

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Abstract

Background

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.

Questions/purposes

We determined whether the Gd-DTPA load in bone cement affected its local tissue distribution over a period of 1 month after local delivery.

Methods

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.

Results

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).

Conclusions

Volume of distribution and duration of Gd-DTPA after local delivery increased with increasing load in the cement and decreased with time.

Clinical Relevance

For local delivery, high antimicrobial concentrations would be expected in greater volumes of tissue, for longer durations, when higher antimicrobial loads are used.

The institution of one or more of the authors (AM, RM) has received, during the study period, funding from the Arizona Biomedical Research Commission (Grant 1116). One of the authors certifies that she (MBG) received funding, during the study period, from the Ira A. Fulton Schools of Engineering and Achievement Rewards for College Scientists with funding support from the Balster-Evani Family. One or more of the authors certify that they (AM, RM) received funding, during the study period, from Banner Good Samaritan Medical Center. One of the authors certifies that he (AM) received funding from the Herbert Louis Fund at Orthopaedic Research and Education Foundation (Rosemont, IL, USA).
All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request.
Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.
This work was performed at Banner Good Samaritan Medical Center, Phoenix, AZ, USA and at Arizona State University, Tempe, AZ, USA.