Postoperative DSSI following spinal fusion surgery is a challenging complication with a potentially catastrophic outcome, as well as significantly increases burden to the patient, patient’s family, and the health-care system. The most common organism isolated from DSSI following spinal fusion surgery is Staphylococcus aureus[16]. However, parenteral vancomycin usage was not as effective as cephalosporin in preventing SSIs in clean orthopedic surgery [17]. Besides, sides effects, such as infusion-related toxicities, nephrotoxicity, red man syndrome and ototoxicity, following parenteral vancomycin could be commonly occurred, even within therapeutic concentration [18]. Although vancomycin impregnated cement is one of the convincing methods to prevent deep infection during knee arthroplasty[19], the role of intra-wound vancomycin power (VP) on DSSI prophylaxis in degenerative lumbar spine fusion surgery is still elusive [4–7],[8, 20].
Bone grafting as a deliver system for VP as adjuvant for DSSI prophylaxis has been reported [6, 11], which was similar to our protocol. Gans I [11] reported 500 mg VP was distributed subfascially and mixed with bone graft in pediatric spine deformity surgery regarding fusion, growing rod, and vertical expandable prosthetic titanium rib (VEPTR). However, the paper focused on the vancomycin-related systemic safety concerns such as anaphylaxis, nephrotoxicity, red man syndrome thrombophlebitis or rash for local application of VP in pediatric patients and did not report the impact of VP on bone fusion. Three (3.4%) in the totally 87 operated pediatric deformity correction still got DSSI at 1 to 2-month postoperatively in the cases series report.
Sweet FA et al [6] reported a retrospective cohort study of applying 2 gm VP locally in almost all kinds of spine instrumented fusion surgeries including transforaminal lumbar interbody fusion, revision surgery, osteotomy, adolescent idiopathic scoliosis, adult scoliosis, trauma and tumor. They spread 1 gm VP deeply and superficially, and the other 1 gm VP was mixed with the bone grafting materials, which was different to our vancomycin protocol, including diversity of the diseases and sprinkling in the wound. In current study, we only focused on degenerative lumbar fusion surgery, and employed VP mixed with the bone grafting materials without sprinkling in the wound. Moreover, the definition of pseudarthrosis was not clearly described in the Sweet’s study[6], which was a major concern for spine surgeons when using VP locally. In our study, we adopted the fusion criteria using Lenke criteria [13] and BSF scale[14] for posterolateral and anterior interbody fusions respectively, which were widely accepted in the literature besides CT scan.
The overall incidences of DSSI in selective degenerative lumbar fusion surgery, adult spine deformity correction, spine trauma surgery and revision instrumented lumbar fusion ranged from 2.8–6% [21], 3.5–4.5%[22, 23], 3–9.4%[24, 25] and 2.2–4.5% [26, 27], respectively. The incidence of DSSI in selective degenerative lumbar fusion surgery is not an uncommon complication, which may have devastating consequence, and spine surgeons need to make an early diagnosis if any clinically suspicious.
Ghobrial GM [28] reported intra-wound vancomycin provided selective pressure with increased gram negative and polymicrobial infection. Chotai S reported [29] the occurrence of DSS caused by S aureus was lower in the V group as compared to those in the NV group (32% vs 65%). A gram-negative pathogen was detected in 28% and 12.5% of patients with DSSI in the V and NV groups, respectively. The incidence of polymicrobial (mixed with anaerobic and aerobic) was similar between two groups (5% for NV group, 4% for V group). Accordingly, significant difference of cultured organisms was observed in the vancomycin group [28, 29]. Neither these papers [28, 29] nor our series were investigated any vancomycin-resistant organisms in DSSI. Clinicians have to be aware of vancomycin-related selective pressure and immune-burden to avoid resistant organism and find a dynamic balance between DSSI prevention and local antibiotics application
Minimal inhibitory concentration (MIC) is defined as the lowest concentration of antimicrobial that will inhibit the visible growth of microorganism following overnight incubation[30]. The mean MIC of vancomycin for MRSA has been reported 1.5-2 µg/mL [31]. In our study, the average vancomycin levels from the surgical site were 517.96 ± 161.72 and 220.14 ± 102.3 µg/mL at POD 1 and POD 3 respectively, which was much higher than the MIC of MRSA and might explain the effect of vancomycin on preventing DSSI postoperatively. Moreover, an undetectable serum vancomycin concentration may explain the little effects on systemic toxicity.
Regarding the inhibition of pre-osteoblast and osteoblast proliferation, three in vitro studies have been reported the vancomycin concentration greater the 3 mg/cm2, 2000 and 5000 µg/mL could inhibit proliferation of pre-osteoblast and osteoblast 9, 34,35, which might lead to nonunion in vivo. The local vancomycin concentrations at POD 1 were 462 and 251 µg/mL have been reported by Sweet FA[6] and Armaghani [32], respectively, and 128 µg/mL at POD 3 by Sweet FA[6]. In our study, the average vancomycin levels were 517.96 ± 161.72 µg/mL (range, 107.9-932.4) and 220.14 ± 102.3 µg/mL (range, 74.3-591.23) at POD 1 and POD 3, respectively, which did not reach the inhibitory concentration for osteoblast. Therefore, the mixture of ABG and bone substitute could serve as a local vancomycin delivery system to maintain high vancomycin concentrations without jeopardizing bony fusion.
There are several drawbacks in our study including patients’ number is not enough to reach and adequate power and draw a solid conclusion. CT scan was not use for fusion evaluation, which is more reliable on examining fusion. Selection bias due to ambispective study was also a weakness. Moreover, intra- and inter-observer reliability for fusion assessment was not checked. Therefore, a prospective randomized study with an adequate patient number is needed to clarify the benefits of vancomycin impregnated autogenous bone graft and bone substitute on preventing DSSI following degenerative lumbar spine fusion surgery.