Basic Science
Does the Effectiveness and Mechanical Strength of Kanamycin-Loaded Bone Cement in Musculoskeletal Tuberculosis Compare to Vancomycin-Loaded Bone Cement

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Abstract

Background

Antibiotic-loaded bone cement (ALBC) is used to deliver antimycobacterial agents into the focal lesion of musculoskeletal tuberculosis. Although kanamycin is currently used as an antimycobacterial agent for the treatment of multidrug-resistant tuberculosis, there is no information about its suitability in ALBC.

Methods

An in vitro experiment was conducted with cylindrical shape of 40 g of bone cement with 1, 2, and 3 g of kanamycin. Eluate (1 mL) was extracted from each specimen to measure the level of elution and antimycobacterial activity on days 1, 4, 7, 14, and 30. The quantity of kanamycin in eluates was evaluated by a liquid chromatography-mass spectrometry system, and the antimycobacterial activity of eluates against Mycobacterium tuberculosis H37Rv was calculated by comparing the minimal inhibitory concentration. The ultimate compression strength was conducted using a material testing system machine (Instron 3366; Instron, Norwood, MA) before and after elution.

Results

Eluates from ALBC containing 2 and 3 g of kanamycin had effective antimycobacterial activity for 30 days, whereas eluates from ALBC containing 1 g of kanamycin were partially active until day 30. The pre-eluted compression strength of kanamycin-loaded cement and vancomycin-loaded cement was weaker as they contained a larger amount of antibiotics. There was no statistical difference between the strength of all kanamycin regimens and 1 g of vancomycin in the ultimate compression test. After 30 days of elution, the strength of all kanamycin-loaded cement and vancomycin-loaded cement cylinders was significantly lower than that of initial specimens (P < .05).

Conclusion

The antimycobacterial activity of ALBC containing more than 2 g of kanamycin was effective during a 30-day period. The ultimate compression strength of bone cement loaded with 1-3 g of kanamycin was comparable with 1 g of vancomycin while maintaining effective elution until day 30.

Section snippets

Preparation of ALBC

For the elution test, 3 doses of antibiotics were mixed with 40 g of bone cement powder not containing antibiotics (CMW 3; DePuy-Synthes, Warsaw, IN). A total of 1, 2, or 3 g of kanamycin (Kanamycin monosulfate; Sigma-Aldrich, Saint Louis, MO) were mixed with bone cement under a sterile environment in the operating room. After adding the liquid monomer, manual mixing of cement powder and kanamycin was performed for 2 minutes, and then, the doughy mixture was molded in a customized frame made of

Results

Kanamycin has been detected in eluates of all regimens during the 30-day eluting period (Fig. 3). Concentrations of all doses had been decreased with time. However, regardless of initial dose mixed, there was no difference in the amount of elution at day 30 (1 g of kanamycin, 3.07 ± 0.42 μg/mL; 2 g of kanamycin, 4.04 ± 1.14 μg/mL; 3 g of kanamycin, 5.11 ± 2.27 μg/mL; P = .372).

Based on the mean MIC values obtained from the experiment (mean MIC value for kanamycin was 1.0 μg/mL), eluates in 2

Discussion

This study demonstrated that more than 2 g of kanamycin-containing bone cement facilitated effective antimycobacterial activity for 30 days. There were no significant difference in mechanical strength between kanamycin and vancomycin, and the kanamycin-containing bone cement showed sufficient strength to meet the international standards for bone cement after a 30-day eluting period.

There are multiple factors that are known to determine the release of antibiotics from ALBC [14,[19], [20], [21],

Conclusion

More than 2 g of kanamycin-loaded bone cement maintained effective elution and antimycobacterial activity until day 30. The mechanical strength of kanamycin was excellent as was that of vancomycin, which is commonly used in forms of ALBC before and after elution. Based on these results, because kanamycin is an antibiotic that has antimicrobial activity against tuberculosis, as well as bacteria, ALBC mixed with more than 2 g of kanamycin might be a considerable material for surgical treatment in

Acknowledgments

The authors thank Chang Hoon Park (Clinical Trials Center, Severance Hospital) and Brain Korea 21 Project for their support in their experiments.

This study was supported by a faculty research grant of Yonsei University College of Medicine, South Korea (6-2017-0156).

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    • One or more of the authors of this paper have disclosed potential or pertinent conflicts of interest, which may include receipt of payment, either direct or indirect, institutional support, or association with an entity in the biomedical field which may be perceived to have potential conflict of interest with this work. For full disclosure statements refer to https://doi.org/10.1016/j.arth.2019.10.023.

    This work was done at the Department of Orthopedic Surgery, Yonsei University College of Medicine, Seoul, Korea.

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