The effect of vancomycin powder on human dural fibroblast culture and its implications for dural repair during spine surgery

Abstract

<jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>Surgical site infections (SSIs) are a major source of morbidity after spinal surgery. Several recent studies have described the finding that applying vancomycin powder to the surgical bed may reduce the incidence of SSI. However, applying vancomycin in high concentrations has been shown in vitro to inhibit osteoblast proliferation and to induce cell death. Vancomycin may have a deleterious effect on dural healing after repair of an intentional or unintentional durotomy. This study was therefore undertaken to assess the effect of different concentrations of vancomycin on a human dura mater cell culture.</jats:p></jats:sec> <jats:sec> <jats:title>METHODS</jats:title> <jats:p>Human dura intended for disposal after decompressive craniectomy was harvested. Explant primary cultures and subcultures were subsequently performed. Cells were characterized through common staining and immunohistochemistry. A growth curve was performed to assess the effect of different concentrations of vancomycin (40, 400, and 4000 μg/ml) on cell count. The effect of vancomycin on cellular shape, intercellular arrangement, and viability was also evaluated.</jats:p></jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>All dural tissue samples successfully developed into fusiform cells, demonstrating pseudopod projections and spindle formation. The cells demonstrated vimentin positivity and also had typical features of fibroblasts. When applied to the cultures, the highest dose of vancomycin induced generalized cell death within 24 hours. The mean (± SD) cell counts for control, 40, 400, and 4000 μg/ml were 38.72 ± 15.93, 36.28 ± 22.87, 19.48 ± 6.53, and 4.07 ± 9.66, respectively (p &lt; 0.0001, ANOVA). Compared with controls, vancomycin-exposed cells histologically demonstrated a smaller cytoplasm and decreased pseudopodia formation resulting in the inhibition of normal spindle intercellular arrangement.</jats:p></jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>When vancomycin powder is applied locally, dural cells are exposed to a concentration several times greater than when delivered systemically. In this in vitro model, vancomycin induced dural cell death, inhibited growth, and altered cellular morphology in a concentration-dependent fashion. Defining a safe vancomycin concentration that is both bactericidal and also does not inhibit normal dural healing is necessary.</jats:p></jats:sec>

Icariin Enhances Bone Repair in Rabbits with Bone Infection during Post-infection Treatment and Prevents Inhibition of Osteoblasts by Vancomycin

“…Moreover, a positive correlation between this effect and the icariin concentration was observed. However, in previous studies, cell numbers were reduced by 50% compared with the control group at 24 h after they were co-cultured with 0.4 mg/mL vancomycin and human dural fibroblast ( Goldschmidt et al, 2016 ). The differences might be due to the variety of species and genera of the cells, and the different characteristics of cellular metabolic activity.…”

“…In fact, a high dose of VCS (more than 1 g of vancomycin) was usually implanted into the local site to control the repeated infection in some cases. In addition, a previous study indicated that a high concentration of vancomycin (more than 4 mg/mL) can decrease the number of osteogenic cells, induce a loss in pseudopodia formation and alter the normal shape of the cytoplasm ( Rathbone et al, 2011 ; Goldschmidt et al, 2016 ).…”

Antibiotikatherapie der pyogenen Spondylodiszitis bei Erwachsenen

“…Ein signifikanter Zelltod wurde bei einer Dosierung über 6 mg/cm 2 beobachtet [57]. Gleichzeitig konnte ein dosisabhängiger negativer Einfluss auf humane durale Zellkuturen beobachtet werden [58]. In vivo konnte in einem Rattenmodell keine höhere Pseudarthroserate bei der Verwendung von Vancomycin als Puderapplikation im Wundbereich mit einer 10fach höheren Dosis als das Gewichtsäquivalent (143 mg/kg Körpergewicht) nachgewiesen werden [59].…”

Do Dose-Dependent Microbial Changes Occur during Spine Surgery as a Result of Applying Intrawound Vancomycin Powder?: A Systematic Literature Review

“…Many articles, including systematic reviews, meta-analyses, and clinical trials, have confirmed that using intrawound vancomycin powder during spine surgery could provide considerable benefits with few side effects [ 1 2 3 4 5 6 7 8 ]. However, some in vitro , animal, and human studies suggest that vancomycin powder inhibits the osteoblast and dural cell viability [ 9 10 11 ]. Furthermore, some studies have shown that using vancomycin intraoperatively has potential risks, including dose-dependent inhibiting effects and changes in microbial trends [ 10 12 13 14 ].…”

“…However, some in vitro , animal, and human studies suggest that vancomycin powder inhibits the osteoblast and dural cell viability [ 9 10 11 ]. Furthermore, some studies have shown that using vancomycin intraoperatively has potential risks, including dose-dependent inhibiting effects and changes in microbial trends [ 10 12 13 14 ]. One retrospective study revealed that the intraoperative microbial trends in surgical site infections appeared to be different in patients in whom intrawound vancomycin powder was used during spine surgery than those in patients who did not; however, the investigators did not examine the relationship between the vancomycin dose used and types of infection bacteria [ 12 ].…”