Correlation between penetration of different types of antibiotics into intervertebral discs and intervertebral disc diffusion function after discitis

Abstract

Objective To measure the intradiscal cefazolin sodium and clindamycin concentrations and explore the reliability of using endplate cartilage diffusion function to predict the intradiscal drug concentration in discitis. Methods Sixty New Zealand white rabbits were chosen to induce discitis. At 1, 2, 4, 8, and 12 weeks after surgery, 12 discitis rabbits were randomly chosen to undergo continuous dynamic contrast-enhanced MRI. The 12 rabbits were divided into two groups, and given a series of 5 half-life courses of intravenous injection of cefazolin sodium and clindamycin, respectively. Serum samples were obtained at one half-life of antibiotic after the last injection. Then, the rabbits were killed immediately and the nucleus pulposus was taken. Concentrations of the two antibiotics in serum and nucleus pulposus tissue were measured by high-pressure liquid chromatography. The permeability of different antibiotics to infected and normal nucleus pulposus at the same time points was compared by the two-sample t-test. The comparisons of intervertebral disc diffusion function and the permeability of the same antibiotic to infected and normal nucleus pulposus at different time points were analyzed by one-way analysis of variance and LSD method. Linear correlation test was used to analyze the correlation between cefazolin sodium and clindamycin concentrations in normal and infected nucleus pulposus and MRI-enhanced signal enhancement intensity values. Results The penetration of cefazolin and clindamycin into the infected disc significantly increased compared with that into the normal disc during the early infection period (1, 2, and 4 weeks) (cefazolin: t=2.05, P=0.032; t=7.71, P<0.001; t=9.70, P<0.001 and clindamycin: t=2.68, P=0.015; t=4.25, P<0.001; t=7.42, P<0.001), and achieved the best at 4 weeks of infection. Then, the penetration of cefazolin and clindamycin gradually decreased during the late period of infection (8 and 12 weeks). There was no significant difference between the infected and normal discs in the penetration of cefazolin at 8 weeks (t=0.70, P=0.183); however, there was a significant difference at 12 weeks (t=-3.88, P<0.001). There was a significant difference in the penetration of clindamycin into the infected and normal discs at 8 (t=-2.57, P=0.010) and 12 weeks (t=-3.13, P=0.010). There were significant differences between the penetration of cefazolin and clindamycin into discs at 1, 2, 4, and 8 weeks post-infection (t=7.37, P<0.001; t=5.28, P<0.001; t=9.72, P<0.001; t=4.94, P<0.001; t=7.83, P<0.001). A positive correlation existed between the penetration of cefazolin into the normal (r=0.922) and infected discs (r=0.898) and the diffuse function. A positive correlation also existed between the penetration of clindamycin into the normal (r=0.923) and infected discs (r=0.896) and the diffuse function. Conclusion The penetration of cefazolin and clindamycin into disc achieves the best at 4 weeks after infection. The permeability of clindamycin is superior to cefazolin and it is easier for clindamycin to achieve a higher concentration in the infected discs. The use of continuous dynamic enhanced MRI to predict the permeability of antibiotic is reliable and effective. Key words: Discitis; Cartilage endplate; Diffusion; Cefazolin; Clindamycin