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Evaluation of Cumulative and Conditional Antibiotic Release from Vancomycin-Embedded Fibrin Sealant and Its Antibacterial Activity : An In Vitro Study

  • Shin, Dong-Won (Department of Neurological Surgery, Inje University Ilsan Paik Hospital, Inje University College of Medicine) ;
  • Sohn, Moon-Jun (Department of Neurological Surgery, Inje University Ilsan Paik Hospital, Inje University College of Medicine) ;
  • Cho, Chong-Rae (Department of Laboratory Medicine, Inje University Ilsan Paik Hospital, Inje University College of Medicine) ;
  • Koo, Hae-won (Department of Neurological Surgery, Inje University Ilsan Paik Hospital, Inje University College of Medicine) ;
  • Yoon, Sang Won (Department of Neurological Surgery, Inje University Ilsan Paik Hospital, Inje University College of Medicine)
  • 투고 : 2019.07.17
  • 심사 : 2019.08.27
  • 발행 : 2020.01.01

초록

Objective : Fibrin sealants have been used for hemostasis, sealant for cerebrospinal fluid leakage, and adhesive barrier in neurosurgery. Further, as its clinical use and role of an effective drug delivery vehicle have been proposed. This study was performed to measure antibacterial activity and continuous local antibiotic release from different concentrations of vancomycin-impregnated fibrin sealant in vitro. Methods : Antibacterial activity was investigated by disk diffusion test by measuring the diameter of the growth inhibition zone of bacteria (methicillin-resistant Staphylococcus aureus, ATCC29213) from vancomycin-embedded fibrin sealant disc diluted at five different concentrations (C1-C5; 8.33, 4.167, 0.83, 0.083, and 0.0083 mg/disc, respectively). Continuous and conditioned release of vancomycin concentration (for 2 weeks and for 5 days, respectively) were also measured using high-performance liquid chromatography (HPLC) method. To mimic the physiologic wound conditions with in vitro, conditioned vancomycin release in phosphate buffer solution (PBS) was measured and replaced PBS for five consecutive days, half a day or completely daily. Results : In the disk diffusion test, the mean diameters of bacterial inhibition zone were 2.54±0.07 cm, 2.61±0.12 cm, and 2.13±0.15 cm (C1, C2, and C3 respectively) but 1.67±0.06 cm and 1.23±0.15 cm in C4 and C5, respectively. Continuous elution test elicited the peak release of vancomycin from the fibrin sealant at 48 hours, with continued release until 2 weeks. However, conditioned vancomycin release decreased to half or more on day 2, however, the sustainable release was measured over the therapeutic dose (10-20 ㎍/mL) for 5 days and 4 days in assays of half and total exchange of PBS. Conclusion : This study suggests that fibrin sealant can provide an efficient vehicle for antibiotic drug release in a wide range of neurosurgical procedures and the safe and effective therapeutic dose will be at the concentration embedded of 4.167 mg/disc or more of vancomycin.

키워드

참고문헌

  1. Abdullah KG, Attiah MA, Olsen AS, Richardson A, Lucas TH : Reducing surgical site infections following craniotomy: examination of the use of topical vancomycin. J Neurosurg 123 : 1600-1604, 2015 https://doi.org/10.3171/2014.12.JNS142092
  2. Ahmad E, Fatima MT, Hoque M, Owais M, Saleemuddin M : Fibrin matrices: the versatile therapeutic delivery systems. Int J Biol Macromol 81 : 121-136, 2015 https://doi.org/10.1016/j.ijbiomac.2015.07.054
  3. Anderson PA, Savage JW, Vaccaro AR, Radcliff K, Arnold PM, Lawrence BD, et al. : Prevention of surgical site infection in spine surgery. Neurosurgery 80(3S) : S114-S123, 2017 https://doi.org/10.1093/neuros/nyw066
  4. Aziz KT, Best MJ, Naseer Z, Skolasky RL, Ponnusamy KE, Sterling RS, et al. : the association of delirium with perioperative complications in primary elective total hip arthroplasty. Clin Orthop Surg 10 : 286-291, 2018 https://doi.org/10.4055/cios.2018.10.3.286
  5. Bernatz JT, Anderson PA : Thirty-day readmission rates in spine surgery: systematic review and meta-analysis. Neurosurg Focus 39 : E7, 2015 https://doi.org/10.3171/2015.7.FOCUS1534
  6. Bhattacharya M, Wozniak DJ, Stoodley P, Hall-Stoodley L : Prevention and treatment of Staphylococcus aureus biofilms. Expert Rev Anti Infect Ther 13 : 1499-1516, 2015 https://doi.org/10.1586/14787210.2015.1100533
  7. Bowler PG, Duerden BI, Armstrong DG : Wound microbiology and associated approaches to wound management. Clin Microbiol Rev 14 : 244-269, 2001 https://doi.org/10.1128/CMR.14.2.244-269.2001
  8. Cashman JD, Jackson JK, Mugabe C, Gilchrist S, Ball K, Tredwell S, et al. : The use of tissue sealants to deliver antibiotics to an orthopaedic surgical site with a titanium implant. J Orthop Sci 18 : 165-174, 2013 https://doi.org/10.1007/s00776-012-0325-6
  9. Charlton-Ouw KM, Kubrusly F, Sandhu HK, Swick MC, Leake SS, Gulbis BE, et al. : In vitro efficacy of antibiotic beads in treating abdominal vascular graft infections. J Vasc Surg 62 : 1048-1053, 2015 https://doi.org/10.1016/j.jvs.2014.03.241
  10. Dessy AM, Yuk FJ, Maniya AY, Connolly JG, Nathanson JT, Rasouli JJ, et al. : Reduced surgical site infection rates following spine surgery using an enhanced prophylaxis protocol. Cureus 9 : e1139, 2017 https://doi.org/10.7759/cureus.1139
  11. Emohare O, Ledonio CG, Hill BW, Davis RA, Polly DW Jr, Kang MM : Cost savings analysis of intrawound vancomycin powder in posterior spinal surgery. Spine J 14 : 2710-2715, 2014 https://doi.org/10.1016/j.spinee.2014.03.011
  12. Eren B, Karagoz Guzey F, Kitis S, Ozkan N, Korkut C : The effectiveness of pedicle screw immersion in vancomycin and ceftriaxone solution for the prevention of postoperative spinal infection: a prospective comparative study. Acta Orthop Traumatol Turc 52 : 289-293, 2018 https://doi.org/10.1016/j.aott.2018.05.004
  13. Grabel ZJ, Boden A, Segal DN, Boden S, Milby AH, Heller JG : The impact of prophylactic intraoperative vancomycin powder on microbial profile, antibiotic regimen, length of stay, and reoperation rate in elective spine surgery. Spine J 19 : 261-266, 2018 https://doi.org/10.1016/j.spinee.2018.05.036
  14. Hake ME, Young H, Hak DJ, Stahel PF, Hammerberg EM, Mauffrey C : Local antibiotic therapy strategies in orthopaedic trauma: practical tips and tricks and review of the literature. Injury 46 : 1447-1456, 2015 https://doi.org/10.1016/j.injury.2015.05.008
  15. Hill BW, Emohare O, Song B, Davis R, Kang MM : The use of vancomycin powder reduces surgical reoperation in posterior instrumented and noninstrumented spinal surgery. Acta Neurochir (Wien) 156 : 749-754, 2014 https://doi.org/10.1007/s00701-014-2022-z
  16. Horowitz B, Busch M : Estimating the pathogen safety of manufactured human plasma products: application to fibrin sealants and to thrombin. Transfusion 48 : 1739-1753, 2008 https://doi.org/10.1111/j.1537-2995.2008.01717.x
  17. Jennings JA, Carpenter DP, Troxel KS, Beenken KE, Smeltzer MS, Courtney HS, et al. : Novel antibiotic-loaded point-of-care implant coating inhibits biofilm. Clin Orthop Relat Res 473 : 2270-2282, 2015 https://doi.org/10.1007/s11999-014-4130-8
  18. Khan NR, Thompson CJ, DeCuypere M, Angotti JM, Kalobwe E, Muhlbauer MS, et al. : A meta-analysis of spinal surgical site infection and vancomycin powder. J Neurosurg Spine 21 : 974-983, 2014 https://doi.org/10.3171/2014.8.SPINE1445
  19. Kroez M, Lang W, Dickneite G : Wound healing and degradation of the fibrin sealant Beriplast P following partial liver resection in rabbits. Wound Repair Regen 13 : 318-323, 2005 https://doi.org/10.1111/j.1067-1927.2005.130315.x
  20. Kummer A, Tafin UF, Borens O : Effect of sonication on the elution of antibiotics from polymethyl methacrylate (PMMA). J Bone Jt Infect 2 : 208-212, 2017 https://doi.org/10.7150/jbji.22443
  21. McConoughey SJ, Howlin RP, Wiseman J, Stoodley P, Calhoun JH : Comparing PMMA and calcium sulfate as carriers for the local delivery of antibiotics to infected surgical sites. J Biomed Mater Res B Appl Biomater 103 : 870-877, 2015 https://doi.org/10.1002/jbm.b.33247
  22. Mintz PD, Mayers L, Avery N, Flanagan HL, Burks SG, Spotnitz WD : Fibrin sealant: clinical use and the development of the University of Virginia Tissue Adhesive Center. Ann Clin Lab Sci 31 : 108-118, 2001
  23. Morishima M, Marui A, Yanagi S, Nomura T, Nakajima N, Hyon SH, et al. : Sustained release of vancomycin from a new biodegradable glue to prevent methicillin-resistant Staphylococcus aureus graft infection. Interact Cardiovasc Thorac Surg 11 : 52-55, 2010 https://doi.org/10.1510/icvts.2010.232447
  24. Najjar PA, Smink DS : Prophylactic antibiotics and prevention of surgical site infections. Surg Clin North Am 95 : 269-283, 2015 https://doi.org/10.1016/j.suc.2014.11.006
  25. Ozaki S, Saito A, Nakaminami H, Ono M, Noguchi N, Motomura N : Comprehensive evaluation of fibrin glue as a local drug-delivery systemefficacy and safety of sustained release of vancomycin by fibrin glue against local methicillin-resistant Staphylococcus aureus infection. J Artif Organs 17 : 42-49, 2014 https://doi.org/10.1007/s10047-013-0746-9
  26. Percival SL : Importance of biofilm formation in surgical infection. Br J Surg 104 : e85-e94, 2017 https://doi.org/10.1002/bjs.10433
  27. Sekhar LN, Natarajan SK, Manning T, Bhagawati D : The use of fibrin glue to stop venous bleeding in the epidural space, vertebral venous plexus, and anterior cavernous sinus: technical note. Neurosurgery 61(3 Suppl) : E51; discussion E51, 2007
  28. Spotnitz WD : Fibrin sealant: past, present, and future: a brief review. World J Surg 34 : 632-634, 2010 https://doi.org/10.1007/s00268-009-0252-7
  29. Strom RG, Pacione D, Kalhorn SP, Frempong-Boadu AK : Decreased risk of wound infection after posterior cervical fusion with routine local application of vancomycin powder. Spine (Phila Pa 1976) 38 : 991-994, 2013 https://doi.org/10.1097/BRS.0b013e318285b219
  30. Theologis AA, Demirkiran G, Callahan M, Pekmezci M, Ames C, Deviren V : Local intrawound vancomycin powder decreases the risk of surgical site infections in complex adult deformity reconstruction: a cost analysis. Spine (Phila Pa 1976) 39 : 1875-1880, 2014 https://doi.org/10.1097/BRS.0000000000000533
  31. Tofuku K, Koga H, Yanase M, Komiya S : The use of antibiotic-impregnated fibrin sealant for the prevention of surgical site infection associated with spinal instrumentation. Eur Spine J 21 : 2027-2033, 2012 https://doi.org/10.1007/s00586-012-2435-4
  32. Toyooka T, Otani N, Wada K, Tomiyama A, Ueno H, Fujii K, et al. : Effect of fibrin glue injection into the cavernous sinus for hemostasis during transcavernous surgery on the cerebral venous draining system. Oper Neurosurg (Hagerstown) 13 : 224-231, 2017 https://doi.org/10.1227/NEU.0000000000001324
  33. Yang L, Wu J, Zhang G, Zhao Z, Fan Z, Wang B : A novel technology: percutaneous injection of fibrin glue as a treatment for frontal sinus cerebrospinal fluid rhinorrhea. J Craniofac Surg 24 : 1646-1649, 2013 https://doi.org/10.1097/SCS.0b013e3182902de6
  34. Yeramaneni S, Robinson C, Hostin R : Impact of spine surgery complications on costs associated with management of adult spinal deformity. Curr Rev Musculoskelet Med 9 : 327-332, 2016 https://doi.org/10.1007/s12178-016-9352-9

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