TY - JOUR
T1 - Progress not panacea
T2 - vancomycin powder efficacy and dose evaluated in an in vivo mouse model of spine implant infection
AU - Park, Howard Y.
AU - Hegde, Vishal
AU - Zoller, Stephen D.
AU - Sheppard, William
AU - Hamad, Christopher
AU - Smith, Ryan A.
AU - Sprague, Marina M.
AU - Proal, Joshua D.
AU - Hoang, John
AU - Loftin, Amanda
AU - Blumstein, Gideon
AU - Burke, Zachary
AU - Cevallos, Nicolas
AU - Scaduto, Anthony A.
AU - Bernthal, Nicholas M.
N1 - Funding Information:
Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Ruth L. Kirschstein National Research Service award T32AR059033 and award 5K08AR069112-0. Further support was provided by the H H Lee Research Program. Author disclosures: HYP: Grant: H H Lee (C); Fellowship Support: NIH (E). VH: Nothing to disclose. SDZ: Nothing to disclose. WS: Nothing to disclose. CH: Nothing to disclose. RAS: Nothing to disclose. MMS: Nothing to disclose. JDP: Nothing to disclose. JH: Nothing to disclose. AL: Nothing to disclose. GB: Nothing to disclose. ZB: Nothing to disclose. NC: Nothing to disclose. AAS: Nothing to disclose. NMB: Consulting: Biomet (E), Bone Support (B), Daiichi Sankyo (E), Onkos (D).
Funding Information:
This study was generously supported in part by the National Institutes of Health and the H H Lee Research Program.
Funding Information:
Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Ruth L. Kirschstein National Research Service award T32AR059033 and award 5K08AR069112-0 . Further support was provided by the H H Lee Research Program.
Publisher Copyright:
© 2019
PY - 2020/6
Y1 - 2020/6
N2 - BACKGROUND: Intrawound vancomycin powder (VP) has been rapidly adopted in spine surgery with apparent benefit demonstrated in limited, retrospective studies. Randomized trials, basic science, and dose response studies are scarce. PURPOSE: This study aims to test the efficacy and dose effect of VP over an extended time course within a randomized, controlled in vivo animal experiment. STUDY DESIGN/SETTING: Randomized controlled experiment utilizing a mouse model of spine implant infection with treatment groups receiving vancomycin powder following bacterial inoculation. METHODS: Utilizing a mouse model of spine implant infection with bioluminescent Staphylococcus aureus, 24 mice were randomized into 3 groups: 10 infected mice with VP treatment (+VP), 10 infected mice without VP treatment (No-VP), and 4 sterile controls (SC). Four milligrams of VP (mouse equivalent of 1 g in a human) were administered before wound closure. Bioluminescence imaging was performed over 5 weeks to quantify bacterial burden. Electron microscopy (EM), bacterial colonization assays (Live/Dead) staining, and colony forming units (CFU) analyses were completed. A second dosing experiment was completed with 34 mice randomized into 4 groups: control, 2 mg, 4 mg, and 8 mg groups. RESULTS: The (+VP) treatment group exhibited significantly lower bacterial loads compared to the control (No-VP) group, (p<.001). CFU analysis at the conclusion of the experiment revealed 20% of mice in the +VP group and 67% of mice in the No-VP group had persistent infections, and the (+VP) treatment group had significantly less mean number of CFUs (p<.03). EM and Live/Dead staining revealed florid biofilm formation in the No-VP group. Bioluminescence was suppressed in all VP doses tested compared with sterile controls (p<.001). CFU analysis revealed a 40%, 10%, and 20% persistent infection rate in the 2 mg, 4 mg, and 8 mg dose groups, respectively. CFU counts across dosing groups were not statistically different (p=.56). CONCLUSIONS: Vancomycin powder provided an overall infection prevention benefit but failed to eradicate infection in all mice. Furthermore, the dose when halved also demonstrated an overall protective benefit, albeit at a lower rate. CLINICAL SIGNIFICANCE: Vancomycin powder is efficacious but should not be viewed as a panacea for perioperative infection prevention. Dose alterations can be considered, especially in patients with kidney disease or at high risk for seroma.
AB - BACKGROUND: Intrawound vancomycin powder (VP) has been rapidly adopted in spine surgery with apparent benefit demonstrated in limited, retrospective studies. Randomized trials, basic science, and dose response studies are scarce. PURPOSE: This study aims to test the efficacy and dose effect of VP over an extended time course within a randomized, controlled in vivo animal experiment. STUDY DESIGN/SETTING: Randomized controlled experiment utilizing a mouse model of spine implant infection with treatment groups receiving vancomycin powder following bacterial inoculation. METHODS: Utilizing a mouse model of spine implant infection with bioluminescent Staphylococcus aureus, 24 mice were randomized into 3 groups: 10 infected mice with VP treatment (+VP), 10 infected mice without VP treatment (No-VP), and 4 sterile controls (SC). Four milligrams of VP (mouse equivalent of 1 g in a human) were administered before wound closure. Bioluminescence imaging was performed over 5 weeks to quantify bacterial burden. Electron microscopy (EM), bacterial colonization assays (Live/Dead) staining, and colony forming units (CFU) analyses were completed. A second dosing experiment was completed with 34 mice randomized into 4 groups: control, 2 mg, 4 mg, and 8 mg groups. RESULTS: The (+VP) treatment group exhibited significantly lower bacterial loads compared to the control (No-VP) group, (p<.001). CFU analysis at the conclusion of the experiment revealed 20% of mice in the +VP group and 67% of mice in the No-VP group had persistent infections, and the (+VP) treatment group had significantly less mean number of CFUs (p<.03). EM and Live/Dead staining revealed florid biofilm formation in the No-VP group. Bioluminescence was suppressed in all VP doses tested compared with sterile controls (p<.001). CFU analysis revealed a 40%, 10%, and 20% persistent infection rate in the 2 mg, 4 mg, and 8 mg dose groups, respectively. CFU counts across dosing groups were not statistically different (p=.56). CONCLUSIONS: Vancomycin powder provided an overall infection prevention benefit but failed to eradicate infection in all mice. Furthermore, the dose when halved also demonstrated an overall protective benefit, albeit at a lower rate. CLINICAL SIGNIFICANCE: Vancomycin powder is efficacious but should not be viewed as a panacea for perioperative infection prevention. Dose alterations can be considered, especially in patients with kidney disease or at high risk for seroma.
KW - Biofilm
KW - Infection
KW - Surgical site infection
KW - Vancomycin powder
UR - https://www.scopus.com/pages/publications/85078043063
UR - https://www.scopus.com/pages/publications/85078043063#tab=citedBy
U2 - 10.1016/j.spinee.2019.12.007
DO - 10.1016/j.spinee.2019.12.007
M3 - Article
C2 - 31863932
AN - SCOPUS:85078043063
SN - 1529-9430
VL - 20
SP - 973
EP - 980
JO - Spine Journal
JF - Spine Journal
IS - 6
ER -