Surgical treatment of Candida albicans spondylodiscitis

Abstract

Introduction:

Spinal infection poses a demanding diagnostic and treatment problem for which a multidisciplinary approach with spine surgeons, radiologists, and infectious disease specialists is required. Infections are usually caused by bacterial microorganisms, although fungal infections can also occur. Most patients with spinal infections diagnosed in the early stages can be successfully managed conservatively with antibiotics, bed rest, and spinal braces. In cases of gross or pending instability, progressive neurological deficits, failure of conservative treatment, spinal abscess formation, severe symptoms indicating sepsis, and failure of previous conservative treatment, surgical treatment is required.

Case presentation:

A 64-year-old male presented to the Outpatient Department with a complaint of pain in bilateral upper extremities for 4 months. The pain was shooting in type, radiating to bilateral arms, forearms, and hands with no aggravating and relieving factors. He is a known case of carcinoma pyriform sinus for which he underwent various cycles of chemotherapy. Ten years later, a tracheostomy was performed for laryngeal edema, and again, an endoscopic gastrostomy was performed due to feeding difficulties. He then developed fever and cervical pain along with pain in the bilateral upper extremities. An infectious etiology was suspected for which multiple antibiotics were started with no positive response. An MRI was performed, which was suggestive of spondylodiscitis probably of tubercular origin. A biopsy was done to confirm the diagnosis, following which antitubercular (HRZE) therapy was started. He was also treated with Duloxetine and gabapentin, which resulted in minor improvements. Subsequent MRIs showed diffuse involvement of the multiple cervical vertebrae along with cord compression. Two stages of anterior corpectomy followed by posterior instrumentation were done. Following the procedure, the patient developed an infection, which was managed with antibiotics. The titanium implant was not removed. A muscle graft was planned with the pectoralis muscle and flap closure was done. The tissue was also sent for Gram stain, AFB stain, and GeneXpert, which showed normal findings. Finally, in tissue culture, Candida albicans was isolated. On performing the enzyme immunoassay test, it was found to be Aspergillus (Galactomannan antigen) positive as well. Antitubercular treatment was stopped. Then, he was managed with an antifungal, oral voriconazole, for the duration of 1 and a half years.

Clinical discussion:

Patients diagnosed with Candida spondylodiscitis tend to have favorable outcomes, likely linked to timely identification, thorough surgical debridement, and proper azole medication. Our case achieved success by promptly identifying and confirming it through tissue culture, detecting spinal cord compression, decompressing it, and initiating specific antifungal treatment. A delay in commencing antifungal therapy has been associated with poorer outcomes, especially in neurological health. Our patient received voriconazole for a full year, suggesting that favorable outcomes are achievable for fungal spondylodiscitis with swift and appropriate surgery and antifungal medication.

Conclusion:

In summary, evaluation for fungal infection is essential in all cases of unexplained spinal infection in immunocompromised patients, regardless of presentation. If the antifungal treatment proves ineffective, a surgical approach is typically employed for the management of fungal spondylodiscitis. Our report details a successful case of fungal spondylodiscitis treated with a surgical approach and highlights the potential for a fungal infection to be a causative factor in noncompressive myelopathy, which may be sometimes mistaken for radiation myelitis.

Introduction

Highlights

• Spinal infection is a challenging condition requiring a multidisciplinary approach, and most cases can be managed conservatively with antibiotics, bed rest, and spinal braces.

• Surgery is required in certain cases of instability, neurological deficits, abscess formation, sepsis, and failure of conservative treatment.

• The case presented is that of a 64-year-old male with bilateral upper extremity pain, diagnosed with spondylodiscitis of probable tubercular origin, who underwent two stages of anterior corpectomy followed by posterior instrumentation and developed a fungal infection postoperatively.

• A surgical approach is typically employed for the management of fungal spondylodiscitis if antifungal treatment proves ineffective.

• This report highlights the potential for fungal infection to be a causative factor in noncompressive myelopathy, which may be sometimes mistaken for radiation myelitis.

Infections of the spine, although uncommon, are extremely destructive and can lead to spinal instability, neurologic damage, including paraplegia, and death if not properly treated¹. Spine infections that involve the vertebrae are called vertebral osteomyelitis or spondylitis. Infections of the spine along with disk spaces are called spondylodiscitis². Most common infections of the spine can be caused by bacteria or fungal etiology. Among the bacterial causes, tubercular infection is quite common in developing countries³. Fungal spondylodiscitis is uncommon even in a large series (0.5–1.6% usually, up to 6.9% in a report)⁴ Candida and Aspergillus are normal commensals of the body that produce disease in susceptible organisms when they gain access to the vascular system through intravenous lines, during the implantation of prosthetic devices, or during surgery⁵. However, cervical spine Candida infections are extremely rare and typically occur only in immunocompromised patients⁶. Clinical features can be radiculopathy, myelopathy, and sensory loss along with local pain and tenderness. Investigations like plain film radiography, computed tomography scan, MR image, and bone scan can be invaluable in the diagnosis of these infections⁷. A definitive diagnosis is established by means of tissue biopsy, histologic evidence, and culture⁸. Treatment of fungal spondylitis is often delayed because of difficulty with the diagnosis⁹. Surgical treatment is required when there is abscess formation, instability, progressive kyphosis secondary to vertebral body collapse, or canal compromise with neurologic deficits¹⁰. Here, we describe the case of a 64-year-old male immunocompromised patient, who attended the Orthopedics Outpatient Department (OPD) with symptoms of bilateral upper extremities pain and upper motor neuron lesion signs for 4 months. Tissue culture was positive for Candida albicans and serology was positive for Aspergillus species.

Case presentation

A 64-year-old male presented to the OPD with a complaint of pain in bilateral upper extremities for 4 months. The pain was shooting in type, radiating to bilateral arms, forearms, and hands with no aggravating or relieving factors.

The patient had a history of carcinoma pyriform sinus, for which he had undergone 35 cycles of radiotherapy and 6 cycles of chemotherapy in 2010 AD. After a year, he presented with difficulty breathing and swelling in his face and neck. Because of significant laryngeal edema, an emergency tracheostomy was performed in January 2021. The patient subsequently underwent a percutaneous endoscopic gastrostomy due to difficulty feeding. Later, he had a sudden onset of hematemesis in May 2021 and was diagnosed with right carotid blowout syndrome, for which coil embolization was done.

After that incident, in May 2021, he developed fever and cervical pain along with pain in the bilateral upper extremities. An infectious etiology was suspected, for which multiple antibiotics were used without any positive response. The MRI finding was suggestive of spondylodiscitis probably of tubercular origin (Fig. 1). Then, a biopsy was done, which was reported as the presence of mixed inflammatory infiltrates with bone erosion, and bone remodeling was empirically started on antitubercular therapy (HRZE regimen) following which the fever subsided and showed a sign of improvement. However, due to nonrelieving pain for 4 months, he presented to our OPD.

Figure 1.

T2 sagittal MR image done in May 2021 showing T2 high signal intensity within the cord with minimal bulge. Arrow shows T2 high signal intensity within the C5–C6 disk space. Other vertebrae also showed some patchy high signal intensity.

On examination, the motor function of the bilateral upper extremities was 4/5. The sensory function was 1/2 — International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). Triceps and biceps jerks were increased. The upgoing plantar reflex (Babinski sign) was positive. The bowel and bladder functions were normal.

Investigation findings showed CBC: 8300/cu mm, erythrocyte sedimentation rate (ESR): 23, and C-reactive protein (CRP): 32. Blood culture was negative for the growth of any organism. Subsequently, a repeat MRI was performed, which showed diffuse involvement of the multiple cervical vertebrae as well as disk spaces, predominantly C5, C6, and C7 levels along with epidural components causing spinal cord compression (Fig. 2).

Figure 2.

T1 postcontrast sagittal MR image (done in August 2021) showing diffuse enhancement of the epidural component (Blue arrow) as well as the involvement of the multiple vertebral bodies and spinal cord compression.

He then planned for two stages of anterior corpectomy followed by posterior instrumentation. During the procedure, we approached the right side to save the intact left carotid artery since he had a history of right carotid blowout syndrome. However, due to his previous radiation therapy, the muscles were very stiff. Hence, it was difficult to reach the cervical vertebra through the anterior approach. The cervical vertebra could be approached with the help of an ENT surgeon. Finally, anterior corpectomy of C5 and C6 was followed by the insertion of a titanium implant (expandable cage) was performed (Fig. 3). However, following the procedure, he had an infection at the surgical site. The wound culture was sent. It was positive for Escherichia coli and hence the antibiotic ceftazidime, which was sensitive to E. coli was started. In addition, regular debridement of the wound was performed. Ceftazidime continued for 6 weeks. However, his implant was not removed assuming the titanium implant is resistant to biofilm formation. He had a deranged renal function test at that time due to which a CT scan could not be performed. A muscle graft was planned for him where the medial part of the pectoralis major muscle was harvested (Fig. 4) and inserted through the wound to cover the implant, plugged into the pyriformis sinus, and tied to the tongue. The procedure was performed by a team of plastic surgeons and orthopedics. The muscle flap helped control the infection. Following the anterior corpectomy, the histopathological report from the cervical spine showed findings suggestive of chronic osteomyelitis. The tissue was also sent for Gram stain, AFB stain, and GeneXpert, which showed normal findings. Finally, in tissue culture, C. albicans was isolated. On performing the enzyme immunoassay test, it was found to be Aspergillus (Galactomannan antigen) positive as well. Antitubercular treatment was stopped. Then, he was managed with an antifungal, oral voriconazole for the duration of 1-year.

Figure 3.

Anterior cervical corpectomy of C5 and C6 followed by insertion of a titanium implant (expandable cage).

Figure 4.

Medial part of the pectoralis major muscle harvested and inserted through the wound to cover the implant, plugged into the pyriformis sinus, and tied to the tongue.

Finally, posterior instrumentation with titanium implants was performed after 3 weeks (Fig. 5). In May 2022, a contrast MRI of the cervical spine was performed, which did not show any sign of infection in the implant site. Following surgery, the patient reported a more pronounced improvement in his symptoms. After 1-year of surgery, the tracheostomy was removed, and now percutaneous endoscopic gastrostomy removal is planned.

Figure 5.

Posterior instrumentation following anterior corpectomy.

Discussion

Spondylodiscitis is a term that encompasses vertebral osteomyelitis, spondylitis, and discitis, all of which are regarded as various presentations of the same clinical disease². Spondylodiscitis is a rare disease accounting for 2–7% of all cases of pyogenic osteomyelitis, with incidence varying from 1 per 100 000/year to 1 per 250 000/year¹¹. Among the causative organisms, the most common organism is Staphylococcus aureus with a high prevalence of tubercular causes predominantly in immunocompromised patients, but the fungal cause is a rare entity⁸. Infections in the spine can be described etiologically as pyogenic, granulomatous (tuberculous, brucella, fungal), and parasitic². Fungal infections of the spine are noncaseating, acid-fast-negative infections that are primarily opportunistic infections in immunocompromised patients⁹. Our patient is an elderly man with a history of carcinoma pyriform sinus who was previously managed with multiple cycles of radiotherapy and chemotherapy.

Candida spp., Aspergillus spp., and Cryptococcus neoformans occur worldwide, while the dimorphic fungi Coccidioidesimmitis and Blastomycesdermatitidis are endemic in certain geographic areas with Candida being the most common species among them⁵. In our patient, C. albicans was isolated through the tissue culture. The most common location of spondylodiscitis caused by Candida is in the lumbar spine, and the presence of neurological deficit is infrequent⁷. However, in our patient, the site of infection was the cervical spine.

The average period between the first symptoms and diagnosis has been reported to be 2–6 months¹². Our patient presented with a duration of 1 month. Clinically, diseases like bacterial osteomyelitis and a high clinical index of suspicion may be required to perform appropriate cultures to establish a diagnosis¹³. In our case, the blood culture was negative for any organisms, but the tissue culture was positive for C. albicans. Subsequently, his blood was sent for fungal antigen testing, which also showed a positive galactomannan test. The laboratory parameters to be determined are leukocytes, CRP, and erythrocyte sedimentation rate, which are massively increased in acute infections, whereas these may be normal or exhibit threshold increases in patients with chronic disease⁸. In our patient, all other parameters were normal except for increased CRP.

In differentiating with the fungal infection in MRI, a band like T2 hypointensity is noted in the subchondral region of the vertebral body probably due to the ferromagnetic and paramagnetic elements within the fungi and the paraspinal collection can have a thick and irregular wall as in the pyogenic collection. However, skip lesions and subligamentous spread can be common findings in Aspergillus and tuberculosis¹². In our case as well, MRI was not confirmatory for the etiology of the spinal infection. Although initially empiric antitubercular therapy was initiated assuming it to be due to tubercular origin, it was not justified as antitubercular therapy is contraindicated in those without a confirmatory diagnosis of tuberculosis.

Also, myelopathic changes as seen in Figure 1 have significantly improved in the follow-up imaging in (Fig. 6). The radicular pain experienced by the patient can be correlated with the imaging, which also disappeared within the course of time. Various articles have noted fungal infection as one of the important causes of noncompressive myelopathy¹³.

Figure 6.

Follow-up imaging after one and a half years.

Spondylodiscitis requires immediate debridement of the focus with decompression and stabilization through a ventral approach when conservative management fails. Otherwise, severe complications occur, such as sepsis, vertebral body destruction, abscess, or neurological deficits¹⁴. In our case, there was diffuse damage to the C5 and C6 vertebrae along with features of upper motor neuron lesions. Prompt surgery for his condition helped the patient in early recovery.

A safe and effective method for patients who require surgery is one-stage extrafocal posterior stabilization combined with anterior debridement and anterior column rebuilding with bone grafts or titanium cages¹⁵. In comparison to autologous bone grafts, titanium cages have been demonstrated to be biomechanically favorable, particularly in cases of significant damage, and are not associated with greater rates of infection persistence or recurrence¹⁶. In our case as well, the titanium implant was not removed but instead, was treated with muscle flap coverage for the surgical site infection along with weeks of antibiotics and debridement. The principle of open surgical debridement is the exploration of the wound to establish if the infection is deep versus superficial, which will further aid on the debridement of necrotic and infected tissue depending on the level. Early involvement of a wound-care team is helpful in the management of postoperative spine infection, as sometimes multiple debridement is necessary¹⁷ Early onset infections can be successfully treated without instrumentation removal and 4–6 weeks of IV antibiotics followed by a course of oral antibiotics of 4–12 weeks¹⁸. Late-onset infections require instrumentation removal¹⁸. Immediate local muscle flap closure following complex spine surgery on high-risk patients is associated with an acceptable rate of wound complications and, as the data in the following cited article demonstrates¹⁹, is safe and effective. Consideration should be given to immediate muscle flap closure in appropriately selected patients¹⁹. The follow-up MRI after one and a half years was suggestive of a healthy implant site.

Patients with Candida spondylodiscitis have better outcomes, which may be associated with prompt recognition, radical surgical debridement, and azole therapy²⁰. The success in our case was due to early diagnosis and confirmation by tissue culture along with the identification of spinal cord compression and spinal decompression, and the start of specific antifungal treatment. It has been suggested that a delay in the start of antifungal therapy is associated with a worse outcome, particularly the neurological one²¹. Our patient was kept on voriconazole for the duration of 1-year. This asserts that a good outcome can be expected in fungal spondylodiscitis with prompt appropriate surgery and antifungal drugs.

Conclusion

The diagnosis and treatment of fungal spondylitis is often challenging, which can lead to delayed treatment and poorer neurologic outcomes. To hasten diagnosis, it is recommended to perform fungal cultures whenever a spinal infection is suspected. Immunecompromised patients should be evaluated for spondylodiscitis caused by Candida. If the antifungal treatment proves ineffective, a surgical approach is typically employed for the management of fungal spondylitis. Patients should be informed of the many potential complications of the disease and given a guarded prognosis. For early postoperative complications such as infection, debridement, and IV antibiotics should be considered. Additionally, figures show that fungal infection can be a possible cause of noncompressive myelopathy, which can be resolved with appropriate treatment. The work has been reported in line with the SCARE 2020 criteria.²²

Ethical approval

Ethical approval for this study was provided by the Ethical Committee of Hospital of Advanced Medicine and Surgery (HAMS), Kathmandu, Nepal, on 17 December 2022.

Consent

Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Patient perspective

Patient was content with the treatment approach. He states that he was finally ‘relieved’ after chronic suffering.

Sources of funding

None.

Conflicts of interest disclosure

The authors declare that they have no financial conflict of interest with regard to the content of this report.

Provenance and peer review

Not commissioned, externally peer-reviewed.