Effects of Intraoperative Intrawound Antibiotic Administration on Spinal Fusion: A Comparison of Vancomycin and Tobramycin in a Rat Model

Wataru Ishida, Alexander Perdomo-Pantoja, Benjamin D. Elder, John Locke, Christina Holmes, Timothy F Witham, Sheng-fu Lo

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Local, intrawound use of antibiotic powder, such as vancomycin and tobramycin, in spinal fusion surgery has become an increasingly common prophylactic measure in an attempt to reduce rates of postsurgical infection. However, the effects of localized antibiotic delivery on fusion remain unclear. The objective of this study was to examine the in vivo effects of intraoperative local delivery of 2 antibiotics commonly used in bone-grafting surgery on spinal fusion outcomes in a rat model. METHODS: Single-level (L4-L5), bilateral posterolateral intertransverse process lumbar fusion surgery was performed on 60 female Lewis rats (6 to 8 weeks of age) using syngeneic iliac crest allograft mixed with clinical bone-graft substitute and varying concentrations of antibiotics (n = 12 each): (1) control without any antibiotics, (2) low-dose vancomycin (14.3 mg/kg), (3) high-dose vancomycin (71.5 mg/kg), (4) low-dose tobramycin (28.6 mg/kg), and (5) high-dose tobramycin (143 mg/kg). Eight weeks postoperatively, fusion was evaluated via micro-computed tomography (µCT), manual palpation, and histological analysis, with blinding to treatment group. In the µCT analysis, fusion-mass volumes were measured for each rat. Each spine specimen (L4-L5) was rated (manual palpation score) on a scale of 2 to 0 (2 = fused, 1 = partially fused, and 0 = non-fused). RESULTS: The mean fusion-mass volume on µCT (mm) was as follows: control, 29.3 ± 6.2; low-dose vancomycin, 26.3 ± 8.9; high-dose vancomycin, 18.8 ± 7.9; low-dose tobramycin, 32.7 ± 9.0; and high-dose tobramycin, 43.8 ± 11.9 (control versus high-dose vancomycin, p < 0.05; and control versus high-dose tobramycin, p < 0.05). The mean manual palpation score for each group was as follows: control, 1.46 ± 0.58; low-dose vancomycin, 0.86 ± 0.87; high-dose vancomycin, 0.68 ± 0.62; low-dose tobramycin, 1.25 ± 0.71; and high-dose tobramycin, 1.32 ± 0.72 (control versus high-dose vancomycin, p < 0.05). The histological analyses demonstrated a similar trend with regard to spinal fusion volume. CONCLUSIONS: Intraoperative local application of vancomycin, particularly at a supraphysiological dosage, may have detrimental effects on fusion-mass formation. No inhibitory effect of tobramycin on fusion-mass formation was observed. CLINICAL RELEVANCE: When spine surgeons decide to use intraoperative intrawound antibiotics in spinal fusion surgery, they should weigh the reduction in surgical site infection against a possible inhibitory effect on fusion.

Original languageEnglish (US)
Pages (from-to)1741-1749
Number of pages9
JournalThe Journal of bone and joint surgery. American volume
Volume101
Issue number19
DOIs
StatePublished - Oct 2 2019

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Spinal Fusion
Tobramycin
Vancomycin
Anti-Bacterial Agents
Palpation
Spine
Tomography
Bone Substitutes
Surgical Wound Infection
Cone-Beam Computed Tomography
Bone Transplantation
Powders
Allografts
Transplants

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

Cite this

Effects of Intraoperative Intrawound Antibiotic Administration on Spinal Fusion : A Comparison of Vancomycin and Tobramycin in a Rat Model. / Ishida, Wataru; Perdomo-Pantoja, Alexander; Elder, Benjamin D.; Locke, John; Holmes, Christina; Witham, Timothy F; Lo, Sheng-fu.

In: The Journal of bone and joint surgery. American volume, Vol. 101, No. 19, 02.10.2019, p. 1741-1749.

Research output: Contribution to journalArticle

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title = "Effects of Intraoperative Intrawound Antibiotic Administration on Spinal Fusion: A Comparison of Vancomycin and Tobramycin in a Rat Model",
abstract = "BACKGROUND: Local, intrawound use of antibiotic powder, such as vancomycin and tobramycin, in spinal fusion surgery has become an increasingly common prophylactic measure in an attempt to reduce rates of postsurgical infection. However, the effects of localized antibiotic delivery on fusion remain unclear. The objective of this study was to examine the in vivo effects of intraoperative local delivery of 2 antibiotics commonly used in bone-grafting surgery on spinal fusion outcomes in a rat model. METHODS: Single-level (L4-L5), bilateral posterolateral intertransverse process lumbar fusion surgery was performed on 60 female Lewis rats (6 to 8 weeks of age) using syngeneic iliac crest allograft mixed with clinical bone-graft substitute and varying concentrations of antibiotics (n = 12 each): (1) control without any antibiotics, (2) low-dose vancomycin (14.3 mg/kg), (3) high-dose vancomycin (71.5 mg/kg), (4) low-dose tobramycin (28.6 mg/kg), and (5) high-dose tobramycin (143 mg/kg). Eight weeks postoperatively, fusion was evaluated via micro-computed tomography (µCT), manual palpation, and histological analysis, with blinding to treatment group. In the µCT analysis, fusion-mass volumes were measured for each rat. Each spine specimen (L4-L5) was rated (manual palpation score) on a scale of 2 to 0 (2 = fused, 1 = partially fused, and 0 = non-fused). RESULTS: The mean fusion-mass volume on µCT (mm) was as follows: control, 29.3 ± 6.2; low-dose vancomycin, 26.3 ± 8.9; high-dose vancomycin, 18.8 ± 7.9; low-dose tobramycin, 32.7 ± 9.0; and high-dose tobramycin, 43.8 ± 11.9 (control versus high-dose vancomycin, p < 0.05; and control versus high-dose tobramycin, p < 0.05). The mean manual palpation score for each group was as follows: control, 1.46 ± 0.58; low-dose vancomycin, 0.86 ± 0.87; high-dose vancomycin, 0.68 ± 0.62; low-dose tobramycin, 1.25 ± 0.71; and high-dose tobramycin, 1.32 ± 0.72 (control versus high-dose vancomycin, p < 0.05). The histological analyses demonstrated a similar trend with regard to spinal fusion volume. CONCLUSIONS: Intraoperative local application of vancomycin, particularly at a supraphysiological dosage, may have detrimental effects on fusion-mass formation. No inhibitory effect of tobramycin on fusion-mass formation was observed. CLINICAL RELEVANCE: When spine surgeons decide to use intraoperative intrawound antibiotics in spinal fusion surgery, they should weigh the reduction in surgical site infection against a possible inhibitory effect on fusion.",
author = "Wataru Ishida and Alexander Perdomo-Pantoja and Elder, {Benjamin D.} and John Locke and Christina Holmes and Witham, {Timothy F} and Sheng-fu Lo",
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T1 - Effects of Intraoperative Intrawound Antibiotic Administration on Spinal Fusion

T2 - A Comparison of Vancomycin and Tobramycin in a Rat Model

AU - Ishida, Wataru

AU - Perdomo-Pantoja, Alexander

AU - Elder, Benjamin D.

AU - Locke, John

AU - Holmes, Christina

AU - Witham, Timothy F

AU - Lo, Sheng-fu

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N2 - BACKGROUND: Local, intrawound use of antibiotic powder, such as vancomycin and tobramycin, in spinal fusion surgery has become an increasingly common prophylactic measure in an attempt to reduce rates of postsurgical infection. However, the effects of localized antibiotic delivery on fusion remain unclear. The objective of this study was to examine the in vivo effects of intraoperative local delivery of 2 antibiotics commonly used in bone-grafting surgery on spinal fusion outcomes in a rat model. METHODS: Single-level (L4-L5), bilateral posterolateral intertransverse process lumbar fusion surgery was performed on 60 female Lewis rats (6 to 8 weeks of age) using syngeneic iliac crest allograft mixed with clinical bone-graft substitute and varying concentrations of antibiotics (n = 12 each): (1) control without any antibiotics, (2) low-dose vancomycin (14.3 mg/kg), (3) high-dose vancomycin (71.5 mg/kg), (4) low-dose tobramycin (28.6 mg/kg), and (5) high-dose tobramycin (143 mg/kg). Eight weeks postoperatively, fusion was evaluated via micro-computed tomography (µCT), manual palpation, and histological analysis, with blinding to treatment group. In the µCT analysis, fusion-mass volumes were measured for each rat. Each spine specimen (L4-L5) was rated (manual palpation score) on a scale of 2 to 0 (2 = fused, 1 = partially fused, and 0 = non-fused). RESULTS: The mean fusion-mass volume on µCT (mm) was as follows: control, 29.3 ± 6.2; low-dose vancomycin, 26.3 ± 8.9; high-dose vancomycin, 18.8 ± 7.9; low-dose tobramycin, 32.7 ± 9.0; and high-dose tobramycin, 43.8 ± 11.9 (control versus high-dose vancomycin, p < 0.05; and control versus high-dose tobramycin, p < 0.05). The mean manual palpation score for each group was as follows: control, 1.46 ± 0.58; low-dose vancomycin, 0.86 ± 0.87; high-dose vancomycin, 0.68 ± 0.62; low-dose tobramycin, 1.25 ± 0.71; and high-dose tobramycin, 1.32 ± 0.72 (control versus high-dose vancomycin, p < 0.05). The histological analyses demonstrated a similar trend with regard to spinal fusion volume. CONCLUSIONS: Intraoperative local application of vancomycin, particularly at a supraphysiological dosage, may have detrimental effects on fusion-mass formation. No inhibitory effect of tobramycin on fusion-mass formation was observed. CLINICAL RELEVANCE: When spine surgeons decide to use intraoperative intrawound antibiotics in spinal fusion surgery, they should weigh the reduction in surgical site infection against a possible inhibitory effect on fusion.

AB - BACKGROUND: Local, intrawound use of antibiotic powder, such as vancomycin and tobramycin, in spinal fusion surgery has become an increasingly common prophylactic measure in an attempt to reduce rates of postsurgical infection. However, the effects of localized antibiotic delivery on fusion remain unclear. The objective of this study was to examine the in vivo effects of intraoperative local delivery of 2 antibiotics commonly used in bone-grafting surgery on spinal fusion outcomes in a rat model. METHODS: Single-level (L4-L5), bilateral posterolateral intertransverse process lumbar fusion surgery was performed on 60 female Lewis rats (6 to 8 weeks of age) using syngeneic iliac crest allograft mixed with clinical bone-graft substitute and varying concentrations of antibiotics (n = 12 each): (1) control without any antibiotics, (2) low-dose vancomycin (14.3 mg/kg), (3) high-dose vancomycin (71.5 mg/kg), (4) low-dose tobramycin (28.6 mg/kg), and (5) high-dose tobramycin (143 mg/kg). Eight weeks postoperatively, fusion was evaluated via micro-computed tomography (µCT), manual palpation, and histological analysis, with blinding to treatment group. In the µCT analysis, fusion-mass volumes were measured for each rat. Each spine specimen (L4-L5) was rated (manual palpation score) on a scale of 2 to 0 (2 = fused, 1 = partially fused, and 0 = non-fused). RESULTS: The mean fusion-mass volume on µCT (mm) was as follows: control, 29.3 ± 6.2; low-dose vancomycin, 26.3 ± 8.9; high-dose vancomycin, 18.8 ± 7.9; low-dose tobramycin, 32.7 ± 9.0; and high-dose tobramycin, 43.8 ± 11.9 (control versus high-dose vancomycin, p < 0.05; and control versus high-dose tobramycin, p < 0.05). The mean manual palpation score for each group was as follows: control, 1.46 ± 0.58; low-dose vancomycin, 0.86 ± 0.87; high-dose vancomycin, 0.68 ± 0.62; low-dose tobramycin, 1.25 ± 0.71; and high-dose tobramycin, 1.32 ± 0.72 (control versus high-dose vancomycin, p < 0.05). The histological analyses demonstrated a similar trend with regard to spinal fusion volume. CONCLUSIONS: Intraoperative local application of vancomycin, particularly at a supraphysiological dosage, may have detrimental effects on fusion-mass formation. No inhibitory effect of tobramycin on fusion-mass formation was observed. CLINICAL RELEVANCE: When spine surgeons decide to use intraoperative intrawound antibiotics in spinal fusion surgery, they should weigh the reduction in surgical site infection against a possible inhibitory effect on fusion.

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