Antimicrobial Distribution From Local Delivery Depends on Dose
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
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.
- Adams K, Couch L, Cierny G, Calhoun J, Mader JT. In vitro and in vivo evaluation of antibiotic diffusion from antibiotic-impregnated polymethylmethacrylate beads. Clin Orthop Relat Res. 1992;278:244–252.
- Aime S, Delli Castelli D, Fedeli F, Terreno E. A paramagnetic MRI-CEST agent responsive to lactate concentration. J Am Chem Soc. 2002;124:9364–9365. CrossRef
- Altman DG. Practical Statistics for Medical Research. 2nd ed. Boca Raton, FL: Chapman & Hall/CRC; 2006.
- Buchholz HW, Elson RA, Engelbrecht E, Lodenkämper H, Röttger J, Siegel A. Management of deep infection of total hip replacement. J Bone Joint Surg Br. 1981;63:342–353.
- Butterfield JM, Patel N, Pai MP, Rosano TG, Drusano GL, Lodise TP. Refining vancomycin protein binding estimates: identification of clinical factors that influence protein binding. Antimicrob Agents Chemother. 2011;55:4277–4282. CrossRef
- Cierny G 3rd, Mader JT, Penninck JJ. A clinical staging system for adult osteomyelitis. Clin Orthop Relat Res. 2003;414:7–24. CrossRef
- Coyle MB. Manual of Antimicrobial Susceptibility Testing. Washington, DC: American Society for Microbiology; 2005.
- Cunningham B, McLaren A, Pauken C, McLemore R. Liposomal formulation increases local delivery of amphotericin from bone cement: a pilot study. Clin Orthop Relat Res. 2012;470:2671–2676. CrossRef
- De Kievit TR, Parkins MD, Gillis RJ, Srikumar R, Ceri H, Poole K, Iglewski BH, Storey DG. Multidrug efflux pumps: expression patterns and contribution to antibiotic resistance in Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother. 2001;45:1761–1770. CrossRef
- Diefenbeck M, Mückley T, Hofmann GO. Prophylaxis and treatment of implant-related infections by local application of antibiotics. Injury. 2006;37(suppl 2):S95–S104. CrossRef
- DiResta GR, Manoso MW, Naqvi A, Zanzonico P, Smith-Jones P, Tyler W, Morris C, Healey JH. Bisphosphonate delivery to tubular bone allografts. Clin Orthop Relat Res. 2008;466:1871–1879. CrossRef
- Dufour P, Gillet Y, Bes M, Lina G, Vandenesch F, Floret D, Etienne J, Richet H. Community-acquired methicillin-resistant Staphylococcus aureus infections in France: emergence of a single clone that produces Panton-Valentine leukocidin. Clin Infect Dis. 2002;35:819–824. CrossRef
- Giers MB, Estes CS, McLaren AC, Caplan MR, McLemore R. Jeannette Wilkins Award. Can locally delivered gadolinium be visualized on MRI? A pilot study. Clin Orthop Relat Res. 2012;470:2654–2662. CrossRef
- Giers MB, McLaren AC, Plasencia JD, Frakes D, McLemore R, Caplan MR. Spatiotemporal quantification of local drug delivery using MRI. Comput Math Methods Med. 2013;2013:149608. CrossRef
- Hanssen AD. Local antibiotic delivery vehicles in the treatment of musculoskeletal infection. Clin Orthop Relat Res. 2005;437:91–96. CrossRef
- Hanssen AD, Spangehl MJ. Practical applications of antibiotic-loaded bone cement for treatment of infected joint replacements. Clin Orthop Relat Res. 2004;427:79–85. CrossRef
- Iarikov D, Demian H, Rubin D, Alexander J, Nambiar S. Choice and doses of antibacterial agents for cement spacers in treatment of prosthetic joint infections: review of published studies. Clin Infect Dis. 2012;55:1474–1480. CrossRef
- Kweon C, McLaren AC, Leon C, McLemore R. Amphotericin B delivery from bone cement increases with porosity but strength decreases. Clin Orthop Relat Res. 2011;469:3002–3007. CrossRef
- Lewis G, Bhattaram A. Influence of a pre-blended antibiotic (gentamicin sulfate powder) on various mechanical, thermal, and physical properties of three acrylic bone cements. J Biomater Appl. 2006;20:377–408. CrossRef
- Mangoni AA, Jackson SH. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol. 2004;57:6–14. CrossRef
- McLaren A, Nugent M, Economopoulos K, Kaul H, Vernon B, McLemore R. Hand-mixed and premixed antibiotic-loaded bone cement have similar homogeneity. Clin Orthop Relat Res. 2009;467:1693–1698. CrossRef
- Miller R, McLaren A, Leon C, McLemore R. Mixing method affects elution and strength of high-dose ALBC: a pilot study. Clin Orthop Relat Res. 2012;470:2677–2683. CrossRef
- Nugent M, McLaren A, Vernon B, McLemore R. Strength of antimicrobial bone cement decreases with increased poragen fraction. Clin Orthop Relat Res. 2010;468:2101–2106. CrossRef
- Odgers R, Jarbo K, McLaren A, McLemore R. Distribution of locally delivered antimicrobials is limited by cortical bone: a pilot study. Clin Orthop Relat Res. 2013;471:3141–3146. CrossRef
- Antimicrobial Distribution From Local Delivery Depends on Dose
Clinical Orthopaedics and Related Research®
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Industry Sectors
- Author Affiliations
- 1. Banner Good Samaritan Orthopaedic Residency, Banner Good Samaritan Medical Center, 901 E Willetta Road, 2nd Floor, Phoenix, AZ, 85006, USA
- 2. School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA