Antibiotic-loaded calcium sulfate beads in spinal surgery for patients with spondylodiscitis: a clinical retrospective study

Spondylodiscitis is an uncommon but potentially life-threatening bacterial infection involving the intervertebral disc and adjacent vertebrae [1]. The annual incidence of spondylodiscitis ranges from 0.5 to 2.2/100,000 inhabitants in Europe [2, 3], and the infection commonly tends to affect the elderly or chronically debilitated patients aged over 50 years [4]. Spondylodiscitis shows mortality rates from 2% to 20% and a morbidity rate of more than 7 % [5]. It can be managed either by non-operative measures, including intravenous/oral antibiotics and immobilization, or by surgical intervention [6]. Surgery for spondylodiscitis is indicated for instability, deformity, neurological deficits, unbearable pain, or disease progression [7]. The surgical goal in spondylodiscitis is to debride the infection, identify and reduce the pathogens, stabilize the deformed and unstable segments, and decompress the neural structures [8].

Anterior, posterior and combined approaches have been used for the treatment of spondylodiscitis [9‐16]. However, the optimal surgical treatment remains controversial. Antibiotic-loaded calcium sulfate is widely used in osteomyelitis as a filler of bone defects, but there were only a few reports specifically on antibiotic-loaded carriers to our knowledge [17]. The objective of this retrospective study was to verify the efficiency of antibiotic-loaded calcium sulfate beads applied in a single-stage posterolateral approach for the treatment of spondylodiscitis.

Thirty-two consecutive patients who underwent surgical treatment for lumbar/ thoracic spondylodiscitis at our department from July of 2015 to August of 2020 were retrospectively investigated. All the patients were treated with the proposed procedure. Patients with neurological deficits, instability, progressive pain, or progression on magnetic resonance imaging (MRI)/ computed tomography (CT) despite conservative treatment underwent surgical treatment. Demographic data, including age, gender, involved segment, clinical outcomes and complications were recorded (Table 1). The intra-operative details, results of culture, functional outcome, radiologic outcome, blood loss, ASIA classification, and length of hospital stay were recorded (Table 2). The sagittal deformity was evaluated by Cobb’s methods, which is the angulation of the upper and lower endplates of the collapsed vertebral bodies. The Cobb angle, Visual analogue scale (VAS), Oswestry Disability Index (ODI) at the time of initial diagnosis, the 7th post-operative day, and the last follow-up were compared (Table 3). Radiological investigations such as X-rays and computed tomography (CT) were done to document endplate erosion, cavitation, reduction in disc space, and instability, and magnetic resonance imaging (MRI) was serially done for evaluation of response to treatment pre-op and post-op routinely. Clinical evaluation was performed using the ASIA classification, ODI and VAS. The functional outcome of the study was measured by the modified criteria of Kirkaldy–Willis. All the patients were treated by empirical antibiotic therapy or antibiotics according to the results of microbial culture and sensitivity when available. Patients were treated with intravenous broad spectrum antibiotics for 6-8 weeks followed by oral antibiotics for a total period of 3 months. The antibiotic therapy was withdrawn based on clinical improvements and the infection related laboratory test results, such as the average levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

The demographic details and patients’ characteristics are presented in table 1. Thirty-two consecutive patients who underwent this surgery for spondylodiscitis had been identified from 2015 to 2020 and their data were investigated. The mean duration of follow-up was 25.2 ± 8.1 months (range 12 to 36 months). The surgical incisions were healed without chronic infection, fistula formation. No recurrences were observed in this group. All patients had significant improvement in constitutional symptoms and back pain after surgery. Early ambulation was permitted the next day after the surgery in all patients. No perioperative complications related to instrumentation or decompression were reported.

The mean patient age was 61.1 ± 9.7 years (range 43–82), with 56 % of the cases being female. The intra-operative amount of blood loss was 243.4 ± 92.1 ml (range 120 to 520 ml) and the duration of surgery was 135.0 ± 30.6 min (around 100 to 240 mins). The majority of the cases involved the lumbar region (62.5%), 25% involving the thoracic spine and 12.5% at the thoracolumbar region. Local tissue cultures for all patients and blood cultures for patients with high fever were performed preoperatively. 14 cases (44%) were Staphylococcus aureus, 5 cases (16%) Escherichia coli, 3 cases (9%) Mycobacterium tuberculosis, 1 case (3%) Propionibacterium acnes, and 9 cases (28%) were culture negative.

The average Cobb angle was significantly improved at 19.8 ± 5.1° post-op and had resolved to 19.2 ± 4.9° at final follow-up. There were statistically differences between the pre-op Cobb angle and the post-op angle and the angle at the final follow-up (P<0.001). The VAS and the ODI values on the seventh-day post-op and at the last follow-up were significantly lower compared with those in pre-op period (P < 0.001). Significant differences were found between the post-op and last follow-up. The ESR and CRP returned to normal levels in all patients within 3 months after surgery. The average hospital stay was 52.3 ± 10.0 days. The average time of the new bone formation and peripheral connection in the lesion segment was 4.6±1.1 months (range 3–6 months), judging by plain radiograph and/or CT scan (Fig. 5). At the last follow-up, neurological recovery was observed in all the patients with the previous neurological deficit (Table 2). According to the Kirkaldy-Willis functional criteria, 14 patients were finally evaluated as “excellent”, 17 patients were “good” and one patient was “fair”.

Spondylodiscitis is a most common spinal infection, which affects the vertebral bodies, intervertebral disk, paraspinal tissues, and also the posterior bony elements occasionally [19]. Traditionally, conservative treatment including immobilization and systemic administration of antibiotics is the first choice for pyogenic spondylitis [20, 21]. Surgical treatment is indicated in patients with progressive biomechanical pain, refractoriness to antibiotic therapy, epidural abscesses, neurological impairment or segmental instability [22]. Surgical intervention is recommended as it could relieve pain, maintain vertebral column balance, improve neurologic function, and bring higher quality life [23].

Debridement and reconstruction are two main principles of the surgical treatment of pyogenic spondylitis [24, 25]. The anterior approach provides direct visualization for radical debridement and decompression without affecting the posterior elements, which is the best way to control the infection and promote definitive healing, and it also can warrant adequate and strong reconstruction with modern instrumentation tools [10‐12]. However, anterior surgery alone does not adequately correct kyphosis and could not bear physiological loads, the recurrence of kyphosis following it are difficult to treat [9, 26]. To overcome these limitations, some authors advocated posterior spinal stabilization and fusion. The posterior approach could give better kyphotic deformity correction and vertebral stabilization, fewer complications and less surgical invasiveness [16]. Meanwhile, the infected intervertebral discs, vertebral endplates, and vertebral body tissues could be adequately debrided through a posterior-only approach to assure the excellence of the radiographic and clinical results [13, 15]. However, a considerable portion of authors believed that the posterior-only approach has the drawbacks of insufficient removal of infected tissue compared with the anterior approach [27]. Thus a combination of anterior debridement with posterior fixation is widely used for the treatment of lumbar pyogenic spondylodiscitis [14, 28‐30]. Nevertheless, the combined approach increases the risk of morbidity associated with the prolonged duration of operation, anesthesia times, the additional blood loss and operative trauma [29]. In our study, all the patients underwent a single-stage posterolateral approach, which is an effective method with easy operation, less invasion and stable secure fixation. The debridement performed with Quadrant system and percutaneous pedicle screw fixation was used to minimize the damage to the paraspinal muscles [18]. The function of the facet joints was preserved well enough to maintain the sagittal stability of the spine by tension band effect instead of cantilever effect if the facet joints were removed. This may be the main reason that in our group the final kyphotic Cobb was maintained well during the follow up period in addition to bone cement enhancement for some osteoporotic patients. Moreover, there was no disturbance to the peritoneum, the abdominal vessels, the psoas muscle, and the lumbosacral nerves in this posterolateral procedure.

Antibiotic-loaded cement (AIBC) is widely used to treat or prevent infections in total hip and knee arthroplasty because it can lead to a locally high antibiotic concentration [31]. Nonetheless, the burst release of antibiotics and microbial colonization of the non-degradable cement has led to an advanced investigation for more antibiotic delivery [32]. Calcium sulphate has a long history as antibiotic carrier material, which is a resorbable osteoconductive scaffolds [33]. It also can be mixed with heat-sensitive antibiotics because there is very little temperature rise on curing [17, 34]. The mechanical strength of CS is comparable to cancellous bone and is hydrolyzed slowly in bone, lasting for about 6–12 weeks [35]. The antibiotic-loaded beads demonstrated high bioactivity in preventing and eliminating the residual bacteria, with long periods of sustained efficacy. It's a good solution for the shortcoming of insufficient removal of infected tissue in the posterior procedure. The cement beads could be absorbed completely in about 8-12 weeks after surgery, and new bone gradually formed while antibiotics were released to control the infection. The imaging examination showed the infected site healing well with no recurrence during the follow-up in our series. Percutaneous pedicle screw instrumentation was used to avoid unnecessary muscle dissection and tissue disruption, decrease blood loss and complications, provide immediate stability [36]. Meanwhile, pedicle screws were inserted into the infected and adjacent vertebra to avoid decreasing mechanical stability by longer fixation levels [37]. However, we used longer segmental fixation in patients with severe vertebral body destruction, which made the screw insertion into the infected vertebral body impossible, to ensure postoperative stability. Bone cement enhanced screws were applied to obtain immediate stability after surgery for patients with osteoporosis. With these techniques, all patients could ambulate the second day after surgery.

Antibiotics targeted toward the causative pathogen appear to be the most important factor to determine the success rate of treatment. Identifying the causative pathogens is one of the key factors to achieve cure in our studies. A positive culture was obtained in 23 patients (72%) while Staphylococcus aureus is the most frequent pathogen (73%) in our studies. Systemic antibiotic treatment duration ranged from 6 weeks to 12 weeks, which was consistent with the previous literature description [23]. Appropriate antibiotic therapy based on the causative pathogen is crucial and can lead to good clinical results. After sending blood culture and disc space aspiration, all patients immediately started empirical intravenous antimicrobial therapy. Then, an appropriate antibiotic was administrated according to the results of microbial culture and sensitivity [38].

This study is mainly aimed at patients with bone defects causing spinal instability, kyphosis, or progressive neurological impairment. Percutaneous fixation after the posterolateral debridement could maintain the stability of the spine and correct kyphosis, which could relieve the severe pain of the patients and make early ambulation possible. Our data showed the pain was significantly relieved and the ODI index was significantly increased after surgery, all patients could return to normal life. Internal local immobilization also helps control the infection spreading and make the general recovery earlier. The patients’ ESR and CRP levels decreased significantly 7 days after surgery and returned to normal in a mean of 4 weeks after surgery, indicating that the inflammation was well controlled. The CS antibiotic bone granules were absorbed in 2 to 3 months gradually, and the bony bridge was observed in all patients in a mean of 4.1 months after surgery. The Cobb Angle was maintained at the final follow-up with no kyphotic deformity aggravated compared with the post-op. All the 20 patients with preoperative dysfunction recovered to different degrees after operation, and the excellent and good rate reached to 94.4%.

However, this study has some limitations. The current study is a small-scale retrospective data analysis in a single institution with no control group. We need a prospective controlled study in a large number of patients to more powerfully identify the effectiveness of this technique in future.

Most patients improved significantly not only in their general conditions but also in their neurological status after surgery without any serious complications. The posterolateral debridement and percutaneous fixation combined with antibiotic-loaded calcium sulfate beads filling is a safe and effective procedure for spondylodiscitis in terms of infection control, early mobilization and recovery.