Surgical treatment of unstable spondylodiscitis with posterior instrumentation and bioactive glass (BAG-S53P4): surgical technique and results at medium-term follow-up

Introduction

Pyogenic spondylodiscitis (PS) is an acute infection disorder usually affecting two contiguous vertebral endplates and the intervertebral disk. The estimated global annual incidence is 4–24 cases/million people with an increasing trend (1-5). It is quite rare in healthy subjects, while it occurs most frequently in frail patients affected by several comorbidities (1,2,6). Diabetes, smoking, chronic kidney disease and immunodeficiency are well-known risk factors (1,2,5,7). PS is mainly caused by hematogenous bacterial seeding on the first endplate, due to a low-flow vascular environment, followed by pathogen diffusion into the adjacent disk and the endplate of the contiguous vertebra (1). The most commonly causative pathogens are Staphylococcus aureus (from skin, respiratory and gastrointestinal infections), coagulase-negative staphylococci (from skin infections), and Enterobacterales (mainly from urinary tract infections) (8). Bacterial proliferation mainly occurs in the disk favored by the lack of direct blood flow, causing bone resorption, deformity, and sometimes neurologic impairment (9-11). Differential diagnosis includes non-pyogenic infectious spondylodiscitis, chronic non-bacterial osteomyelitis of the spine, several inflammatory non-infectious spinal disorders and vertebral fractures associated with ureteral injury (12-15). In the last two decades, the improvement of imaging, leading to an earlier diagnosis, and antibiotic therapy has reduced the morbidity and mortality of patients with PS (16); nevertheless, the mortality still ranges from 2% to 20% (5). The long-term outcome of PS is scarce and characterized by chronic back pain and disability, leading to a poor quality of life (17). Several treatments have been proposed in association with antibiotic therapy, ranging from rigid orthosis to debridement and surgical instrumentation (18). Surgical treatment is usually considered when poor pain control, spinal instability, antibiotic therapy failure and/or neurological impairment occur. With regards to spinal instability, the Spinal Instability Spondylodiscitis Score (SISS) has been recently introduced to guide the surgical treatment (19). This score considers the affected levels, the extension of vertebral body involvement, the spinal alignment and the presence of mechanical or inflammatory pain. The PS are so divided into three groups: stable [0–4], potentially unstable [5–9], unstable [10–14] based on the total score obtained. Surgical goals are infection eradication, spinal stabilization, deformity prevention or correction, pain relief, and prevention of neurologic impairment (18,20,21). There are no specific guidelines regarding the surgical timing, however early surgical treatment demonstrated good results in term of relapse and failure, mortality rate, and length of hospital stay (22).

Nevertheless, the risk of infection worsening or persistence exists, due to the potential presence of dead space and the use of implants (23,24). Therefore, the use of local antimicrobial void fillers has been proposed (25,26). Bioactive glass S53P4 (BAG-S53P4) (BonAlive^®) is a bone void filler available in granules of different diameters that, releasing active ions, provides an osmotic antibacterial effect and an alkaline environment that inhibit the adhesion and the colonization of up to 50 different bacteria species (27,28). Its efficacy in osteomyelitis treatment has been widely reported (29,30). Furthermore, with its osteo-stimulative and osteoconductive properties, BAG-S53P4 promotes the intervertebral fusion of the treated segments (30). Nevertheless, until now, to the best of our knowledge, BAG-S53P4 has been used in PS only in association with cages or mesh.

The aims of this article are: (I) to report all the surgical steps needed to perform a correct posterior instrumentation to cure unstable PS, promoting intervertebral fusion and infection control with BAG-S53P4 without the use of other anterior support hardware; (II) to share our experience reporting the results of the first three patients, who safely and successfully underwent this surgery at the department of orthopaedic surgery of the ASST-Ovest Milanese, Legnano Hospital (Italy). We present this article in accordance with the SUPER reporting checklist (31) (available at https://jss.amegroups.com/article/view/10.21037/jss-25-6/rc).

Preoperative preparations and requirements

In 2020–2021 we introduced this novel procedure to treat unstable PS using posterior instrumentation and BAG-S53P4 alone to fill the intervertebral space and promote intervertebral fusion and infection control.

Indication for this surgery: patients presenting uncontrolled pain, spinal instability, progressive deformity despite a correct conservative treatment, as long as the posterior vertebral wall is intact.

Contraindications: compromised patients who cannot undergo surgery, the integrity loss of the posterior vertebral wall, possible hypersensitivity to the materials.

This technique can be easily performed by a trained spine surgeon and requires a specific learning curve. It is recommended to perform this procedure in hospitals with spinal units and intensive care units (ICUs). Intraoperative neurological monitoring may be needed in dorsal levels especially if reduction maneuvers are planned. Standard posterior instrumentation and at least 20 cc of BAG-S53P4 for treated level should be available to perform the surgery.

Our first three patients underwent surgery for progressive spinal instability after a trial of conservative treatment. The patients’ features, surgical and microbiological details, SISS score, antibiotic treatment and results are resumed in Table 1.

All procedures reported in this study were in accordance with the ethical standards of the institutional research committee and with the Helsinki Declaration and its subsequent amendments. ASST Ovest Milanese - Legnano Hospital does not require ethical approval for reporting surgical techniques and case series results with anonymized and unidentified images and data. Nevertheless, all patients included were informed of the possibility of future publications deriving from their treatment and gave their verbal consent for anonymized data publication in any form (including unidentified images, open access publications, etc.).

Case 1

A 76-year-old female, affected by type 2 diabetes mellitus, hypertension, hypercholesterolemia, and atrial fibrillation. She developed L3–L4 hematogenous spondylodiscitis that was initially empirically treated with 4.5 g of piperacillin-tazobactam thrice a day and later with 500 mg of vancomycin every 6 hours. After one month she reported progressively increasing low back pain and right sensitive radiculopathy due to vertebra collapse and to the presence of intraforaminal septic material. She underwent L2–L5 stabilization with laminectomy, foraminotomy, and filling of the disk space and anterior bone cavitation with 15 cc of BAG-S53P4 bioactive glass. Pre, postoperative imaging, and 2-year follow-up computed tomography (CT) scan of case 1 are shown in Figure 1A-1D.

Figure 1 Case 1 imaging, L3–L4 PS. (A) Preoperative X-ray; (B) preoperative sagittal STIR MRI; (C) postoperative X-ray; (D) 2-year follow-up sagittal CT scan. CT, computed tomography; MRI, magnetic resonance imaging; PS, pyogenic spondylodiscitis; STIR, short-T1 inversion recovery.

Case 2

A 73-year-old male, affected by terminal kidney disease on dialysis, hypertension, diabetes complicated by polyneuropathy and retinopathy, previous stroke, chronic obstructive obliterative arteriopathy treated with a femoropopliteal bypass, critical coronary artery disease treated with stent. He was admitted for L2–L3 spondylodiscitis after episodes of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia from the dialysis catheter. The patient first underwent a course of 750 mg of levofloxacin and 600 mg of rifampicin daily. Nevertheless, the patient showed an infection persistence with clinical worsening and high C-reactive protein (CRP) values. Therefore, he underwent a vertebral biopsy that resulted negative for bacterial growth. At this point, for the progression of bone erosion at the infected site and bad response to antibiotic therapy and pain control, we decided to perform a lumbar (L1 to L4) stabilization and fusion using 10 cc of S53P4 bioactive glass in the L2–L3 space. Pre, postoperative imaging, and 3-year follow-up CT-scan of case 2 are shown in Figure 2A-2D.

Figure 2 Case 2 imaging, L2–L3 PS. (A) Preoperative sagittal CT scan; (B) preoperative sagittal T2 MRI; (C) postoperative X-ray; (D) 3-year follow-up sagittal CT-scan. CT, computed tomography; MRI, magnetic resonance imaging; PS, pyogenic spondylodiscitis.

Case 3

An 83-year-old man with a history of chronic obstructive pulmonary disease (COPD), smoke abuse, coronary artery disease treated with multiple stents, previous stroke, hypertension, hypercholesterolemia, benign prostatic hyperplasia, and a non-specified rheumatologic disease, causing progressive spine ankylosis in chronic steroid treatment. He developed a T11–T12 hematogenous PS caused by an extended-spectrum beta-lactamases (ESBL) Escherichia coli urinary infection treated with 4.5 g of piperacillin-tazobactam thrice daily and later with 160–800 mg of trimethoprim-sulfamethoxazole (cotrimoxazole) twice a day. After 1 month of conservative treatment the patient reported general condition deterioration, inability to walk and sit caused by increased back pain and delirium. A new CT-scan revealed progressive spine instability. At this point he underwent a T9–L3 posterior fusion and filling of the T11–T12 space with 12 cc of S53P4 bioactive glass. Pre, postoperative imaging, and 2-year follow-up CT-scan of case 3 are shown in Figure 3A-3D.

Figure 3 Case 3 imaging, T11–T12 PS. (A) Preoperative sagittal CT scan; (B) preoperative sagittal T2 MRI; (C) postoperative X-ray; (D) 2-year follow-up sagittal CT-scan. CT, computed tomography; MRI, magnetic resonance imaging; PS, pyogenic spondylodiscitis.

Step-by-step description

In the operating theatre, the patient is positioned prone under general anesthesia using foam pads to protect the body prominences. Antibiotic prophylaxis is prescribed by an infectious disease consultant based on the specific case and the ongoing or previous antibiotic therapy. The skin is prepared with antimicrobial soap and alcoholic chlorhexidine solution. Sterile drapes are used to isolate the surgical field. At this point the prone alignment of the spine can be checked to verify if the reduction of the deformity has occurred. A posterior incision is made at the selected levels and the spine is reached by dissection. Pedicle screws are inserted at the selected levels. The extension of the instrumentation is based on the region of the spine to be treated, the morphology, the presence of deformity and its grade, the bone loss, and the presence of other surgically or naturally fused levels near the affected region. It may vary from the inclusion of the two adjacent vertebrae affected by the PS if the anterior bone loss is minimal, to several levels above and below, in case of deformity and fusion, e.g., in PS patients affected by ankylosing spondylitis. At this point the intervertebral space that needs to be treated is identified and reached by flavectomy, arthrectomy, hemilaminectomy or bilateral laminectomy based on the level, the morphology of the spine, including the presence of canal stenosis, and the possible coexistence of abscesses that need to be drained. The dura mater and the level’s nerve root are visualized. The nerve can be gently moved cranially to gain access to the axilla, while the dura mater is carefully pushed medially. Careful protection of these structures is mandatory. The annulus fibrosus is incised to gain access to the disk space. Usually, a variable extended cavity is found. The debridement of the cavitation can be achieved with a curette under fluoroscopy guidance, avoiding an excessive anterior curettage. The debrided material should be collected and sent to microbiological analysis. The irrigation of the void space can be performed using a syringe with a locking needle. The BAG-S53P4 previously activated by the injection of saline solution, can now be carefully positioned in small volume and inserted into the cavity using a 3–4-mm tip bone pusher. Initially it should be pushed gently to avoid damage to the anterior structures, later it can be pushed with more strength to distribute it and fill all the space. At the end of the procedure bars are inserted and locked and the wound closed.

Postoperative considerations and tasks

The surgical cost related to the use of BAG-S53P4 is approximately 1,350–2,700 euros higher than a standard posterior stabilization surgery.

Postoperative monitoring in ICU may be necessary for possible hemodynamic instability due to septic embolization due to surgical maneuvers, especially during the bioglass insertion.

After surgery, deep venous thrombosis prophylaxis should be prescribed according to the institution protocols. We usually administer daily 4,000–6,000 international units (UI) of subcutaneous sodic enoxaparin for 1 month.

Antibiotic therapy should be continued according to the infectious disease specialist prescription, usually for a total of 8–12 weeks, including the preoperative period.

An accurate postoperative pain control should be carried out with intravenous and oral pain killers (usually morphine 0.3–0.4 mg/kg daily in continuous infusion, acetaminophen 1 g thrice a day, ketorolac 60–90 mg daily subdivided into 2 or 3 doses).

We do not routinely use rigid orthosis after those surgeries, but they may be prescribed according to the surgeon’s preference. Verticalization and walking with assistance to improve patients’ balance, are allowed from the first postoperative day. Hospital discharge is variable based on patients’ needs and features.

Beyond the postoperative radiographs, the patients are routinely followed up with weekly check of inflammatory markers for the first 6 weeks, and then with serial long standing radiographs, blood count, and CRP evaluation at 6 weeks, 3, 6, 12, and 24 months postoperatively. We request a CT-scan approximately every 12 months to check spinal fusion.

The first three patients were also evaluated through visual analogue scale (VAS) and Oswestry questionnaire before and after the surgery, at 6 weeks, 3, 6, 12, and 24 months after the treatment. They completed 12 weeks of antibiotic therapy with resolution of the infections, documented by the persistent normalization of the CRP values after antibiotic withdrawal. They experienced a progressive resolution of the back pain, with a complete recovery, functional outcome, and residual pain comparable to their levels before the onset of the infection. These results have been confirmed during a minimum of 2-year follow-up period. None of the patients showed adverse reaction to the BAG-S53P4. Only the second patient needed plastic revision of the surgical wound 1 month after the vertebral stabilization, for a non-infected dehiscence due to his bad quality of tissue perfusion. Moreover, he showed partial implant mobilization at the most cranial and caudal levels of the stabilization at the 2-year follow-up, most likely for his poor bone density. However, as he did not complain of any worsening of back pain, and he had no sign of infection recurrence, we did not recommend any revision surgery. Six months after the surgery this patient developed a superficial acute paronychial infection which caused a slight rise of the CRP level, then normalized at the subsequent follow-up.

We observed the same wound complication in another patient on dialysis recently treated, that we did not report because of the short follow-up, due to his death 6 months after the procedure because of an aortic dissection. Nevertheless, his spine had apparently healed from the infection using the same technique at the last available follow-up.

The graphs reporting CRP levels, VAS and Oswestry scores collected before and after the surgeries are reported respectively in the Figures 4-6.

Figure 4 CRP levels trend before and after surgery over the follow-up period of the three patients. CRP, C-reactive protein.

Figure 5 VAS trend before and after surgery over the follow-up period of the three patients. VAS, Visual Analogue Scale.

Figure 6 Oswestry score trends before and after surgery over the follow-up period of the three patients.

Tips and pearls

Preoperative

• Patients should be selected with care. The technique should be reserved to patients showing spinal instability and progressive deformity despite a correct antibiotic therapy.
• The loss of integrity of the posterior wall contraindicates this procedure.

Intraoperative

• The extension of the instrumentation should be decided on a case-by-case basis. When possible, the affected vertebrae should be included in the instrumentation using shorter screws to provide greater stability, reducing the need for more extensive instrumentation.
• We recommend at least a bilateral arthrectomy and partial hemilaminectomy of the affected vertebrae to gain more space into the canal, allowing safer maneuvers in the disk space and improving the posterior elements fusion. Sometimes it is helpful to enlarge the access by removing part of the annulus fibrosus and the edges of the vertebral bodies with a Kerrison rongeur.
• During debridement, the curette should never overpass the anterior spine profile on the fluoroscopy check and its tip should always stay in contact with the bone.
• During bioglass insertion, the bone pusher can be used by adding a rotatory movement while pushing, to help to distribute the granules. Mallets are not needed.

Postoperative

• Postoperative ICU patient management should be planned: hemodynamic instability due to intraoperative septic embolization is not rare.
• A multidisciplinary approach with infectious disease specialists is mandatory to optimize treatment results.

Discussion

The management of the dead space formed after or during an infection is an important part of the surgical treatment (24). Many materials have been used as fillers for bone cavities in bone infections, also in spine surgery (23,32-34). The anterior column debridement and reconstruction can be achieved by cages or meshes surrounded by or filled with bone autograft or allograft (23). However, the use of allograft and metal devices in the setting of an infection can raise concerns about biofilm formation (23,35). In fact, biofilm formation has been demonstrated on several implant materials, including those which the cages are made of, such as titanium and polyether ether ketone (PEEK) (19,36). Therefore, to reduce the risk of infection persistence, the implantation of potentially colonizable materials should be minimized as much as possible. Moreover, anterior debridement or corpectomy and reconstruction, even if they are superior in terms of deformity correction, often require a double procedure (anterior and posterior) in patients usually affected by many comorbidities, with a potential risk of complications. To obtain a better infection control, antibiotic-loaded polymethylmethacrylate (PMMA) and calcium sulphate have also been used (32,34).

Nevertheless, the use of antibiotic-loaded materials carries some problems like the choice of the right drug, the duration of the drug delivery, the possible development of antibiotic resistance, and the potential need of reintervention, if it is not intended to be used as definitive filler.

In those settings, BAG-S53P4 seems to be a reasonable choice. With its broad-spectrum of antimicrobial efficacy, extended to M. tuberculosis, fungi and multi-drug-resistant bacteria (27,28,37), it can be used to act locally without the problem of induced resistances (27,38). The use of BAG-S53P4 in the setting of chronic osteomyelitis is well established, with good infection control (29,33,39). Table 2 resumes the previously published articles on the clinical efficacy of BAG-S53P4 to treat bone infections (29,30,33,40-51).

This feature is extremely useful in the spine infection setting, where biopsies carry out a negative result in 24–52% of cases (23,52). Moreover, in vitro studies showed BAG-S53P4 efficacy even with bacteria in biofilm (53,54). From a reconstruction point of view, S53P4 is an osteostimulative and osteoconductive material with the property to be resorbed and replaced with bone even if over a period of years (30). To accelerate the bone formation, the BAG-S53P4 is often used in a 50% mixture with bone autograft (33).

Another reason that made BAG-S53P4 granules attractive from our standpoint is the possibility to fill a cavity in a more adaptable way than a rigid cage. This, although on the one hand restricts its use to limited bone defects in the anterior column, on the other hand may help to distribute the pressure on a larger and more adaptable surface than rigid cages, including inside the bone endplate cavities, which characterizes PS. As the affected endplates are not even, and rigid cages cannot fill these cavities but lean on the small surface represented by the flat residual part of the vertebral body, they are likely to have a higher risk of subsidence compared to BAG-S53P4 granules, considering also the usual poor bone quality in the setting of patients with spondylodiscitis (55). Using the formula P = F/S where F is the weight force, S the bone surface and P the pressure, it appears that increasing the surface of contact between the upper and the lower affected vertebrae, the pressure in each point of the surface decreases, as the weight force is constant for each person. This should reduce the risk of fracture and subsidence (56). Furthermore, it has been proved that posterior instrumentation is responsible of the greatest part of vertebral stability, significantly reducing the axial load passing by anterior cages (57). This could be the reason why, in our case series, the anterior implantation of BAG-S53P4, together with posterior instrumentation, was enough to obtain stability and fusion, without the additional use of cages. Furthermore, the use of cages inevitably reduces the volume of BAG-S53P4 that can be inserted, hindering its correct distribution in the septic cavities and potentially leaving dead spaces that could contribute to infection persistence.

Other authors reported the use of BAG-S53P4 in the setting of spondylodiscitis (30,33). Kankare et al. successfully treated three patients with BAG-S53P4 to cover cages or meshes sometimes in association with autologous bone and a 4-years follow-up (33).

Lindfors et al. reported one case treated with posterior stabilization, vertebral body substitution with implant surrounded by BAG-S53P4 and a 2-year of follow-up (30).

Recently a retrospective study analyzed the efficacy of another bioactive-glass mixed with an antibiotic elution and autologous bone graft used in a similar manner in 34 cases with good results at 1-year follow-up (25).

However, to the best of our knowledge, this is the first article reporting the use of using the BAG-S53P4 alone as a filler for cavitations and smaller bone defects in spine infections, where surgery is needed but a double approach may appear too aggressive. All the three cases reported achieved bone fusion with BAG-S53P4 and posterior instrumentation within 2 years, despite a preoperative unstable PS according to the SISS score.

This study presents some limitations. This is a novel technique used on a small case series: we are reporting the first three patients, who reached the 2-year follow-up. We are currently using this technique on our patients, but the short follow-up and the limited surgical indications on spondylodiscitis, will allow us to perform a retrospective study with a larger number of patients only in the future. Nevertheless, based on the outcomes of the first three patients, the results are encouraging. Further studies are needed to evaluate the efficacy and complete osteointegration of BAG-S53P4 in the long term and the applicability limits of this technique in PS with a higher degree of instability (SISS score 13–14), where the need of an anterior rigid support (cages or meshes) is most likely.

Conclusions

This report suggests BAG-S53P4 can be a safe product to control dead space in the setting of cavitation induced by spine infections, helping to achieve infection eradication, spine stability and pain control with a good functional outcome in association with posterior spinal stabilization, dead space irrigation and debridement, and systemic antibiotic therapy. There was no need for additional anterior support. A partial bioactive glass resorption and bone substitution were observed during the 2-year follow-up; moreover, we observed a progressive reduction of radiolucency around the bioactive glass. The surrounding bone achieved a complete radiological fusion even if residual BAG-S53P4 was still visible on the imaging.

Acknowledgments

We are very grateful to Professor Robert K. Lark (Duke University, Durham, North Carolina, US) for the language and structure proofreading of this manuscript.

Footnote

Reporting Checklist: The authors have completed the SUPER reporting checklist. Available at https://jss.amegroups.com/article/view/10.21037/jss-25-6/rc

Peer Review File: Available at https://jss.amegroups.com/article/view/10.21037/jss-25-6/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jss.amegroups.com/article/view/10.21037/jss-25-6/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures reported in this study were in accordance with the ethical standards of our institutional and national research committee and with the Helsinki Declaration and its subsequent amendments. Our institution does not require ethical approval for reporting surgical techniques and case series results with anonymized and unidentified images and data. Nevertheless, all patients included were informed of the possibility of future publications deriving from their treatment and gave their verbal consent for anonymized data publication in any form (including unidentified images, open access publications, etc.).

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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