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

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.

How Long Does Antimycobacterial Antibiotic-loaded Bone Cement Have In Vitro Activity for Musculoskeletal Tuberculosis?

BACKGROUND: Antibiotic-loaded bone cement is accepted as an effective treatment modality for musculoskeletal tuberculosis. However, comparative information regarding combinations and concentrations of second-line antimycobacterial drugs, such as streptomycin and amoxicillin and clavulanic acid, are lacking. QUESTIONS/PURPOSES: (1) In antibiotic-loaded cement, is there effective elution of streptomycin and Augmentin® (amoxicillin and clavulanic acid) individually and in combination? (2) What is the antibacterial activity duration for streptomycin- and amoxicillin and clavulanic acid -loaded cement? METHODS: Six different types of bone cement discs were created by mixing 40 g bone cement with 1 or 2 g streptomycin only, 0.6 g or 1.2 g Augmentin® (amoxicillin and clavulanic acid) only, and a combination of 1 g streptomycin plus 0.6 g amoxicillin and clavulanic acid and 2 g streptomycin plus 1.2 g amoxicillin and clavulanic acid. Five bone discs of each type were incubated in phosphate buffered saline for 30 days with renewal of the phosphate buffered saline every day. The quantity of streptomycin and/or amoxicillin and clavulanic acid in eluates were measured by a liquid chromatography-mass spectrometry system, and the antimycobacterial activity of eluates against Mycobacterium tuberculosis H37Rv, were calculated by comparing the minimal inhibitory concentration of each eluate with that of tested drugs using broth dilution assay on microplate. RESULTS: Streptomycin was detected in eluates for 30 days (in 1 g and 2 g discs), whereas 1.2 g amoxicillin and clavulanate eluted until Day 7 and 0.6 g amoxicillin and clavulanate until Day 3. All eluates in streptomycin-containing discs (streptomycin only, and in combination with amoxicillin and clavulanic acid) had effective antimycobacterial activity for 30 days, while amoxicillin and clavulanate-only preparations were only active until Day 14. The antimycobacterial activity of eluates of 2 g streptomycin plus 1.2 g amoxicillin and clavulanate were higher than those of discs containing 1 g streptomycin plus 0.6 g amoxicillin and clavulanate until Day 3, without differences (Day 3, 1 g streptomycin plus 0.6 g amoxicillin and clavulanate: 17.5 ± 6.85 ug/mL; 2 g streptomycin plus 1.2 g amoxicillin and clavulanate: 32.5 ± 16.77 ug/mL; p = 0.109). After Day 7, however, values of the two combinations remained no different than that of Day 30 (Day 30, 1 g streptomycin plus 0.6 g amoxicillin and clavulanate: 0.88 ± 0.34 ug/mL; 2 g streptomycin plus 1.2 g amoxicillin and clavulanate: 0.59 ± 0.94 ug/mL; p = 0.107). CONCLUSIONS: Streptomycin, in the form of antibiotic-loaded bone cement, had effective elution characteristics and antimycobacterial effects during a 30-day period, whereas amoxicillin and clavulanate only had effective elution and antimycobacterial characteristics during the early period of this study. The two drugs did not interfere with each other during the elution test. CLINICAL RELEVANCE: This research revealed that combinations of streptomycin and amoxicillin and clavulanate mixed with bone cement are effective for 30 days. Further trials to determine various different combinations of drugs are necessary to improve the effectiveness of treatments for musculoskeletal tuberculosis.

Isoniazid could be used for antibiotic-loaded bone cement for musculoskeletal tuberculosis: an in vitro study.

BACKGROUND: Antibiotic-loaded bone cement (ALBC) has been used in serious cases of musculoskeletal tuberculosis, but the type and amount of antibiotic that should be used in ALBC have not been determined. QUESTIONS/PURPOSES: We therefore determined the (1) elution characteristics and (2) antimycobacterial activity of isoniazid- and rifampicin-loaded bone cement. METHODS: A total of 240 elution samples of each of three discs from 40 g bone cement mixed with one of eight dosages: 1 g, 2 g, and 4 g isoniazid, 1 g, 2 g, and 4 g rifampicin, and a combination of 1 + 1 g or 2 + 2 g of isoniazid and rifampicin. The polymerization of rifampicin-loaded bone cement was delayed to mean 122.5 ± 31.1 minutes. We measured the quantity of isoniazid and rifampicin and the antimycobacterial activity on Days 1, 3, 7, 14, and 30. RESULTS: Isoniazid eluted in almost all the samples while rifampicin was detected only on Day 1 with 2 g (0.7 ± 0.4 ug/mL/day), and until Day 14 with 4 g (0.1 ± 0.0 ug/mL/day). Most of the samples containing isoniazid showed antimycobacterial activity while the samples containing rifampicin showed antimycobacterial activity only on Day 1 with 1 g (0.52 ± 0.18 ug/mL), until Day 14 with 2 g (0.03 ± 0.00 ug/mL), and until Day 30 with 4 g (1.84 ± 1.90 ug/mL). CONCLUSION: Rifampicin was unsuitable for ALBC because of its delayed polymerization. Isoniazid eluted and showed antimycobacterial activity for 30 days. CLINICAL RELEVANCE: The data suggest isoniazid could be considered for use in ALBC for musculoskeletal tuberculosis if used with systemic treatment. For preventing resistance and systemic toxicity, a combination with a second-line drug and an in vivo study would be needed.