A new in-vitro model to investigate antibiotic penetration of the intervertebral disc

Abstract

We have studied the ability of a range of antibiotics to penetrate intervertebral disc tissue in vitro, using a mouse disc model. Equilibrium concentrations of antibiotics incorporated into the entire disc were determined by bioassay using a microbial growth-inhibition method. Uptake was significantly higher with positively-charged aminoglycosides compared with negatively-charged penicillins and cephalosporins. Uncharged ciprofloxacin showed an intermediate degree of uptake. Our results support the hypothesis that electrostatic interaction between charged antibiotics and negatively-charged glycosaminoglycans in the disc is an important factor in antibiotic penetration, and may explain their differential uptake.

Pyogenic Discitis following Discectomy

“…18 Magnetic resonance imaging at post-discectomy weeks 2 to 3 Isolation of the disc from circulating blood may explain the lack of response to prophylactic antibiotics, and development of intradiscal infection despite minimal bacterial inoculation. The duration of antibiotic prophylaxis should be 24 to 72 hours, 23 although some consider that 24 hours of antibiotic prophylaxis is as beneficial as 48 to 72 hours. [23][24][25][26] Antibiotic prophylaxis expands the golden period.…”

“…Positively charged aminoglycosides, gentamicin, and tobramycin penetrate into the disc more significantly than penicillin and cephalosporins do. 23 Gentamicin-containing collagenous sponges placed in the cleared disc space are effective in preventing discitis. 4,5,27 Tobramycin or cephazolin is recommended.…”

Therapeutic use of cephazolin to prevent complications of spine surgery

“…Low antibiotic recovery may be attributed to the high binding potential of tissue proteins to anionic β-lactam antibiotics and/or due to the avascular structure of the tissue. Previous animal studies have shown mixed results in regards to cephalosporin diffusion into the disc (Boscardin et al, 1992;Eismont et al, 1987;Lang et al, 1995;Fraser et al, 1989;Thomas et al, 1995). Perhaps this is because many factors infl uence the recovery of cephazolin from tissue samples.…”

“…Cephazolin is water soluble, distributed through most body fl uids and tissues (including joints, bone and soft tissues) and continues to be a reasonable choice for prophylaxis. However, timing of administration of cephazolin to prevent infection remains unclear, along with the ability of the antibiotic to penetrate all components of the disc (Eismont et al, 1987;Thomas et al, 1995;Gibson et al, 1987). Despite a better prognosis for the patient, who receives prophylactic antibiotics, attempts to understand the action of antibiotics in the disc are lacking.…”

“…The charge of this region infl uences the distribution of molecules throughout the disc. Therefore, the entry and effectiveness of some antibiotics will be infl uenced because of mutually repellant charges between the antibiotic and the proteoglycans (Currier et al, 1994;Eismont et al, 1987;Gibson et al, 1987;Thomas et al, 1995). While there are many methods for detecting cephazolin in serum and vascular organs (Beovic et al, 1999;Galanti et al, 1996;Gupta and Stewart, 1980;How et al, 1998;Hume et al, 1983;Lanao et al, 1988;Liang et al, 1994;Low et al, 2000;Polk et al;, Walker et al, 1986Watanabe et al, 1980;Wold and Turnipseed, 1977) few methods are applicable to the avascular intervertebral disc (Boscardin et al, 1992;Riley, 1998;Fraser et al, 1989).…”