Journal of the Korean Association of Oral and Maxillofacial Surgeons

  • 제48권2호
  • /
  • Pages.94-100
  • /
  • 2022
  • /
  • 2234-7550(pISSN)
  • /
  • 2234-5930(eISSN)
대한구강악안면외과학회 (The Korean Association of Oral and Maxillofacial Surgeons)
권호 표지
DOI QR코드

DOI QR Code

Comparative effects of systemic administration of levofloxacin and cephalexin on fracture healing in rats

  • Golestani, Shayan (Department of Oral and Maxillofacial Surgery, Dental School, Islamic Azad University, Isfahan (Khorasgan) Branch) ;
  • Golestaneh, Arash (Department of Oral and Maxillofacial Surgery, Dental School, Islamic Azad University, Isfahan (Khorasgan) Branch) ;
  • Gohari, Atousa Aminzadeh (Department of Oral Pathology, Dental School, Islamic Azad University, Isfahan (Khorasgan) Branch)
  • 투고 : 2021.12.18
  • 심사 : 2022.03.15
  • 발행 : 2022.04.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Objectives: This study aimed to compare the effects of systemic administration of levofloxacin or cephalexin on fracture healing in rats. Materials and Methods: In this animal study, tibial fractures not requiring fixation were artificially induced in 30 male Wistar albino rats using a 1.1 mm surgical bur. The rats were randomly divided into 6 groups (n=5). Groups 1 and 2 received daily subcutaneous saline injections. Groups 3 and 4 received subcutaneous injections of 25 mg/kg levofloxacin twice daily. Groups 5 and 6 received daily subcutaneous injections of 20 mg/kg cephalexin. The rats in Groups 1, 3, and 5 were sacrificed after 1 week, while the rats in Groups 2, 4, and 6 were sacrificed after 4 weeks. The score of fracture healing was determined through histological assessment of sections from the fracture site according to Perry and colleagues. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests. Results: The mean score of fracture healing at 4 weeks was significantly higher than that at 1 week in the saline, levofloxacin, and cephalexin groups (P<0.001). At 1 week, no significant difference was noted among the three groups of saline, levofloxacin, and cephalexin in the mean score of fracture healing (P=0.360). However, this difference was significant at 4 weeks (P=0.018), and the mean score in the saline group was significantly higher compared to that in the levofloxacin group (P=0.015). Conclusion: It is recommended not to prescribe levofloxacin for more than 1 week after surgical management of bone fractures due to its possible adverse effects on fracture healing.

키워드

참고문헌

  1. Shokier H, Khalifa G, Fawzy A, Sallam MM. Experimental use of autogenous bone grafts as an alternative method for bone plates in treatment of mandibular fracture. Aust J Basic Appl Sci 2010;4:1466-72.
  2. Ucan MC, Koparal M, Agacayak S, Gunay A, Ozgoz M, Atilgan S, et al. Influence of caffeic acid phenethyl ester on bone healing in a rat model. J Int Med Res 2013;41:1648-54. https://doi.org/10.1177/0300060513490613
  3. Hausman MR, Schaffler MB, Majeska RJ. Prevention of fracture healing in rats by an inhibitor of angiogenesis. Bone 2001;29:560-4. https://doi.org/10.1016/s8756-3282(01)00608-1
  4. Keramaris NC, Calori GM, Nikolaou VS, Schemitsch EH, Giannoudis PV. Fracture vascularity and bone healing: a systematic review of the role of VEGF. Injury 2008;39 Suppl 2:S45-57. https://doi.org/10.1016/S0020-1383(08)70015-9
  5. Cook JJ, Summers NJ, Cook EA. Healing in the new millennium: bone stimulators: an overview of where we've been and where we may be heading. Clin Podiatr Med Surg 2015;32:45-59. https://doi.org/10.1016/j.cpm.2014.09.003
  6. MalekiGorji M, Golestaneh A, Razavi SM. The effect of two phosphodiesterase inhibitors on bone healing in mandibular fractures (animal study in rats). J Korean Assoc Oral Maxillofac Surg 2020;46:258-65. https://doi.org/10.5125/jkaoms.2020.46.4.258
  7. Massari L, Caruso G, Sollazzo V, Setti S. Pulsed electromagnetic fields and low intensity pulsed ultrasound in bone tissue. Clin Cases Miner Bone Metab 2009;6:149-54.
  8. Perry AC, Prpa B, Rouse MS, Piper KE, Hanssen AD, Steckelberg JM, et al. Levofloxacin and trovafloxacin inhibition of experimental fracture-healing. Clin Orthop Relat Res 2003;414:95-100. https://doi.org/10.1097/01.blo.0000087322.60612.14
  9. Maxwell A. The molecular basis of quinolone action. J Antimicrob Chemother 1992;30:409-14. https://doi.org/10.1093/jac/30.4.409
  10. Rissing JP. Antimicrobial therapy for chronic osteomyelitis in adults: role of the quinolones. Clin Infect Dis 1997;25:1327-33. https://doi.org/10.1086/516150
  11. Davis R, Bryson HM. Levofloxacin. A review of its antibacterial activity, pharmacokinetics and therapeutic efficacy. Drugs 1994;47:677-700. https://doi.org/10.2165/00003495-199447040-00008
  12. Shahabadi N, Hashempour S. DNA binding studies of antibiotic drug cephalexin using spectroscopic and molecular docking techniques. Nucleosides Nucleotides Nucleic Acids 2019;38:428-47. https://doi.org/10.1080/15257770.2018.1562071
  13. Papich MG, Lindeman C. Cephalexin susceptibility breakpoint for veterinary isolates: Clinical Laboratory Standards Institute revision. J Vet Diagn Invest 2018;30:113-20. https://doi.org/10.1177/1040638717742434
  14. Huddleston PM, Steckelberg JM, Hanssen AD, Rouse MS, Bolander ME, Patel R. Ciprofloxacin inhibition of experimental fracture healing. J Bone Joint Surg Am 2000;82:161-73. https://doi.org/10.2106/00004623-200002000-00002
  15. Atalay Y, Gunes N, Guner MD, Akpolat V, Celik MS, Guner R. Pentoxifylline and electromagnetic field improved bone fracture healing in rats. Drug Des Devel Ther 2015;9:5195-201. https://doi.org/10.2147/DDDT.S89669
  16. Clark JD, Gebhart GF, Gonder JC, Keeling ME, Kohn DF. Special report: the 1996 guide for the care and use of laboratory animals. ILAR J 1997;38:41-8. https://doi.org/10.1093/ilar.38.1.41
  17. Krischak GD, Augat P, Blakytny R, Claes L, Kinzl L, Beck A. The non-steroidal anti-inflammatory drug diclofenac reduces appearance of osteoblasts in bone defect healing in rats. Arch Orthop Trauma Surg 2007;127:453-8. https://doi.org/10.1007/s00402-007-0288-9
  18. Sitovs A, Voiko L, Kustovs D, Kovalcuka L, Bandere D, Purvina S, et al. Pharmacokinetic profiles of levofloxacin after intravenous, intramuscular and subcutaneous administration to rabbits (Oryctolagus cuniculus). J Vet Sci 2020;21:e32. https://doi.org/10.4142/jvs.2020.21.e32
  19. Williams BH. Therapeutics in ferrets. Vet Clin North Am Exot Anim Pract 2000;3:131-53, vi. https://doi.org/10.1016/s1094-9194(17)30098-1
  20. Hernandez RK, Do TP, Critchlow CW, Dent RE, Jick SS. Patient-related risk factors for fracture-healing complications in the United Kingdom General Practice Research Database. Acta Orthop 2012;83:653-60. https://doi.org/10.3109/17453674.2012.747054
  21. Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, et al.; American Society of Health-System Pharmacists (ASHP); Infectious Diseases Society of America (IDSA); Surgical Infection Society (SIS); Society for Healthcare Epidemiology of America (SHEA). Clinical practice guidelines for antimicrobial prophylaxis in surgery. Surg Infect (Larchmt) 2013;14:73-156. https://doi.org/10.1089/sur.2013.9999
  22. Pountos I, Georgouli T, Bird H, Kontakis G, Giannoudis PV. The effect of antibiotics on bone healing: current evidence. Expert Opin Drug Saf 2011;10:935-45. https://doi.org/10.1517/14740338.2011.589833
  23. Kallala R, Graham SM, Nikkhah D, Kyrkos M, Heliotis M, Mantalaris A, et al. In vitro and in vivo effects of antibiotics on bone cell metabolism and fracture healing. Expert Opin Drug Saf 2012;11:15-32. https://doi.org/10.1517/14740338.2012.643867
  24. Holtom PD, Pavkovic SA, Bravos PD, Patzakis MJ, Shepherd LE, Frenkel B. Inhibitory effects of the quinolone antibiotics trovafloxacin, ciprofloxacin, and levofloxacin on osteoblastic cells in vitro. J Orthop Res 2000;18:721-7. https://doi.org/10.1002/jor.1100180507
  25. Salzmann GM, Naal FD, von Knoch F, Tuebel J, Gradinger R, Imhoff AB, et al. Effects of cefuroxime on human osteoblasts in vitro. J Biomed Mater Res A 2007;82:462-8. https://doi.org/10.1002/jbm.a.31158
  26. Edin ML, Miclau T, Lester GE, Lindsey RW, Dahners LE. Effect of cefazolin and vancomycin on osteoblasts in vitro. Clin Orthop Relat Res 1996;333:245-51.
  27. Brown SA. Fluoroquinolones in animal health. J Vet Pharmacol Ther 1996;19:1-14. https://doi.org/10.1111/j.1365-2885.1996.tb00001.x
  28. Martinez M, McDermott P, Walker R. Pharmacology of the fluoroquinolones: a perspective for the use in domestic animals. Vet J 2006;172:10-28. https://doi.org/10.1016/j.tvjl.2005.07.010
  29. Forster C, Kociok K, Shakibaei M, Merker HJ, Stahlmann R. Quinolone-induced cartilage lesions are not reversible in rats. Arch Toxicol 1996;70:474-81. https://doi.org/10.1007/s002040050301
  30. Gough A, Johnson R, Campbell E, Hall L, Tylor J, Carpenter A, et al. Quinolone arthropathy in immature rabbits treated with the fluoroquinolone, PD 117596. Exp Toxicol Pathol 1996;48:225-32. https://doi.org/10.1016/S0940-2993(96)80003-0
  31. Kato M, Takada S, Ogawara S, Takayama S. Effect of levofloxacin on glycosaminoglycan and DNA synthesis of cultured rabbit chondrocytes at concentrations inducing cartilage lesions in vivo. Antimicrob Agents Chemother 1995;39:1979-83. https://doi.org/10.1128/AAC.39.9.1979
  32. Linseman DA, Hampton LA, Branstetter DG. Quinolone-induced arthropathy in the neonatal mouse. Morphological analysis of articular lesions produced by pipemidic acid and ciprofloxacin. Fundam Appl Toxicol 1995;28:59-64. https://doi.org/10.1006/faat.1995.1146
  33. Shakibaei M, Kociok K, Forster C, Vormann J, Gunther T, Stahlmann R, et al. Comparative evaluation of ultrastructural changes in articular cartilage of ofloxacin-treated and magnesium-deficient immature rats. Toxicol Pathol 1996;24:580-7. https://doi.org/10.1177/019262339602400507
  34. Egerbacher M, Edinger J, Tschulenk W. Effects of enrofloxacin and ciprofloxacin hydrochloride on canine and equine chondrocytes in culture. Am J Vet Res 2001;62:704-8. https://doi.org/10.2460/ajvr.2001.62.704
  35. Egerbacher M, Seiberl G, Wolfesberger B, Walter I. Ciprofloxacin causes cytoskeletal changes and detachment of human and rat chondrocytes in vitro. Arch Toxicol 2000;73:557-63. https://doi.org/10.1007/s002040050008
  36. Stahlmann R, Schwabe R. Safety profile of grepafloxacin compared with other fluoroquinolones. J Antimicrob Chemother 1997;40 Suppl A:83-92. https://doi.org/10.1093/jac/40.suppl_1.83
  37. Forster C, Rucker M, Shakibaei M, Baumann-Wilschke I, Vormann J, Stahlmann R. Effects of fluoroquinolones and magnesium deficiency in murine limb bud cultures. Arch Toxicol 1998;72:411-9. https://doi.org/10.1007/s002040050521
  38. Menschik M, Neumuller J, Steiner CW, Erlacher L, Koller M, Ullrich R, et al. Effects of ciprofloxacin and ofloxacin on adult human cartilage in vitro. Antimicrob Agents Chemother 1997;41:2562-5. https://doi.org/10.1128/AAC.41.11.2562
  39. Long F, Ornitz DM. Development of the endochondral skeleton. Cold Spring Harb Perspect Biol 2013;5:a008334. https://doi.org/10.1101/cshperspect.a008334