Prompted by relatively high infection rates associated with surgical treatment of pediatric spinal conditions such as scoliosis and spinal-deformity surgery in immunocompromised adults, spine surgeons have led “deep dive” clinical research into the possible benefits of local, intrawound antibiotic therapy. Consequently, the administration of antibiotic powder around the spine’s posterior elements and internal-fixation devices has become fairly widespread. But are there possible downsides to this approach that can impact patient outcomes?
This important question is addressed in the basic-science study by Ishida et al. in the October 2, 2019 issue of The Journal. The authors analyzed the fusion-specific impact of varying concentrations of intrawound vancomycin and tobramycin in a well-characterized rat model of posterolateral fusion performed with syngeneic iliac-crest allograft plus clinical bone-graft substitute. Ishida et al. found that a high dose of vancomycin (71.5 mg/kg, about 5 times higher than spine surgeons typically use) but not tobramycin had detrimental effects on fusion-mass formation in this model, as demonstrated by micro-computed tomography and histological analysis.
We now need further clinical research from the spine community to determine the optimal doses and types of intrawound antibiotics in this setting. Based on the currently available data, power calculations should be performed when designing future trials focused on this question. There seems to be little remaining doubt that locally delivered antibiotics help limit surgical-site and deep infections in spinal surgery. The impact of antibiotics on fusion rates must now be investigated further.
Marc Swiontkowski, MD
JBJS Editor-in-Chief
Ishida et al. offer insight into the possible role of vancomycin, particularly “supraphysiological” intrawound doses, in spinal fusion in a rat model.
However, it is unclear whether the authors considered the translation of results from in vitro studies using human osteoblasts when applying them to a live rat model. For example, using the principle of allometry, the human equivalent daily dose of vancomycin for rat doses of 150 mg/kg and 200 mg/kg would approximate to 24.2 mg/kg and 32.3 mg/kg, respectively (1). It is uncertain how the authors calculated physiological or “supraphysiological” doses for rat osteoblasts.
The authors also did not control for extraossesus effects, such as nephrotoxicity, which may indirectly affect bone healing and fusion. It is well-established that bone healing is affected by severe renal dysfunction. The apparent lack of renal-function monitoring (or acknowledgment of such in their report) generates further concern.
The possibility of certain antibiotics affecting bone healing and spinal fusion when placed in the wound at high dose is an intriguing one, and Ishida et al. offer more fuel for speculation. However, the lack of discussion in their report about translation between human studies and rat models is worrisome, particularly in the modern age of evidence-based medicine.
Reference
1. Rhodes, et al. Evaluation of Vancomycin Exposures Associated with Elevations in Novel Urinary Biomarkers of Acute Kidney Injury in Vancomycin-Treated Rats. Antimicrob Agents Chemother. 2016 Oct; 60(10): 5742–5751. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038238/