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Progress not panacea: vancomycin powder efficacy and dose evaluated in an in vivo mouse model of spine implant infection

Abstract

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.

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