|Year : 2020 | Volume
| Issue : 2 | Page : 243-249
Postoperative fungal discitis in immune-competent patients: A series of five patients
Arpit S Upadhyay, Mihir R Bapat, Bharat K Patel, Amandeep Gujral
Spine Surgery Department, Nanavati Super Speciality Hospital, Nanavati Institute of Spine Surgery (NISS), Mumbai, Maharashtra, India
|Date of Submission||31-May-2019|
|Date of Decision||13-Aug-2019|
|Date of Acceptance||06-Nov-2019|
|Date of Web Publication||13-Jul-2020|
Dr. Arpit S Upadhyay
Spine Surgery Department, Nanavati Super Speciality Hospital, Nanavati Institute of Spine Surgery (NISS), 1st Floor, Main Building, S.V. Road, Vile Parle West, Mumbai, Maharashtra.
Source of Support: None, Conflict of Interest: None
Introduction: Postoperative fungal discitis is a rare phenomenon and sparse data are available concerning the cause and adequate treatment guidelines especially in immune-competent patients. This case series reports fungal spondylodiscitis in five immune-competent patients after minimal access spine surgery. Study Design: Retrospective observational study. Materials and Methods: Retrospectively five patients with postoperative fungal discitis were studied. Spine radiographs, gadolinium contrast magnetic resonance imaging, and hematological markers (erythrocyte sedimentation rate/C-reactive protein) were performed in all patients. All patients underwent posterior debridement and stabilization procedure followed by antifungal therapy at our center. The clinical outcomes in the form of Oswestry disability index (ODI) and visual analog scale (VAS) scores were recorded before index surgery, 3 months, and at final follow-up. Results: All patients, four men and one woman with an average age of 55.2 years (45–61), had primary coincidental minimal access spine surgery. The average delay from the primary surgery to onset of pain was 6.4 weeks (4–10 weeks). The average delay from the onset of symptoms, postprimary surgery to secondary surgery, at the author’s institution was 13.2 weeks (11–16 weeks). Preoperative values of ODI and VAS were significantly decreased from 78.8 and 8.2 to 14.4 and 1.4, respectively, at the final follow-up. There was one case of recurrence at adjacent level 3 months after antifungal treatment requiring a revision surgery and recommencement of antifungal treatment. Conclusion: A high index of suspicion is required for prompt diagnosis. Fungal study should be routinely included in tissues biopsied for infective etiology. Antifungal treatment of adequate duration with surgical debridement and stabilization should be the mainstay of treatment.
Keywords: Disinfection and sterilization, immune-competent patient, minimal access spine surgery, postoperative fungal discitis
|How to cite this article:|
Upadhyay AS, Bapat MR, Patel BK, Gujral A. Postoperative fungal discitis in immune-competent patients: A series of five patients. Indian Spine J 2020;3:243-9
|How to cite this URL:|
Upadhyay AS, Bapat MR, Patel BK, Gujral A. Postoperative fungal discitis in immune-competent patients: A series of five patients. Indian Spine J [serial online] 2020 [cited 2020 Aug 15];3:243-9. Available from: http://www.isjonline.com/text.asp?2020/3/2/243/289651
| Introduction|| |
Postoperative discitis, although rare, is one of the most dreaded complication of any spine procedure. Varying asepsis standards and operative techniques, which involves excessive soft-tissue handling and aggressive disc preparation, have been cited as an important causative factors. Treatment consists of debridement and adequate antibiotic administration., The occurrence of pyogenic infection is minimized to less than 1% by diligent surgical technique, theater asepsis, and use of antibiotics. Micro-endoscopic lumbar surgery ensures rapid alleviation of pain, patient safety, and short hospital stay. Varying sterilization standards and use of antibiotics sans fixed protocol have permitted atypical infections to come to fore. One such atypical infection is fungal infection. Fungal infections are usually common in immune-compromised patients and their occurrence in immune-competent patient is so infrequent that many a times they are overlooked or misdiagnosed.,,
Ordering for a fungal study in a postsurgical discitis requires extreme level of suspicion particularly in an immune-competent patient. We present a series of five patients of postoperative fungal discitis where we try to analyze the cause, mode of inoculation, and the management of postoperative fungal discitis.
| Material and Methods|| |
A retrospective analysis of the patient records mentioning postoperative fungal discitis who presented to our institution between 2014 and 2016 were studied. Only immune-competent patients with postoperative fungal discitis were included in the study. Patients with spontaneous fungal discitis, postoperative discitis in immune-compromised, and pyogenic/tubercular discitis were excluded. Patients were termed “immune-competent” due to the absence of diabetes, HIV, malignancy, chemotherapy, and malnourishment. All patients led an active and healthy lifestyle till onset of pain.
At the author’s institution, all patients underwent radiographs of lumbo-sacral spine (antero-posterior and lateral) and gadolinium contrast magnetic resonance imaging (MRI). Computed tomography (CT) scan was done on two patients for osteomyelitis. Blood markers––erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)––were observed in all patients. A posterior surgical debridement, interbody fusion using polyetheretherketone (PEEK) cage and pedicle screw stabilization was done in all the patients. In one patient, previous implant had loosened and backed out, so preexisting screws were replaced with larger diameter screws. As a protocol, all debrided tissue samples were sent for histopathology and microbiology for aerobic, anaerobic, mycobacterial, and fungal studies. In the microbiology study, tissue samples were plated on sheep blood agar, sheep chocolate agar, MacConkey agar, Sabouraud dextrose agar, and brain heart infusion blood agar (BHIBA) medium. In all patients, the pyogenic and mycobacterial cultures returned negative. The fungi cultured on sabouraud dextrose agar medium were further processed for antibiotic sensitivity on slide culture (filamentous fungi) and vitek compact II (non-filamentous fungi).
The antifungal regimen was formulated by an infectious disease specialist with due consideration to the immune-competent status of the patients [Table 1]. Postoperatively, all patients had regular follow-up at 3, 6, 9, and 12 weeks and thereafter 3 monthly till 1 year and then twice in the second year. ESR, CRP, complete leukocyte count, and radiographs were obtained at each visit. MRI was obtained at 3 months. Functional outcomes using visual analog scale (VAS) and Oswestry disability index (ODI) scores were recorded preoperatively at 3 months and at the final follow-up (24–38 months and average of 29 months).
| Results|| |
The patients were primarily operated by incidental “minimal access surgery” techniques. Four underwent posterior endoscopic discectomy and one minimally invasive interbody fusion (tubular system) [Table 1]. All patients were operated at secondary care centers before being referred to the author’s institution––a tertiary care center. There were no perioperative adverse events (prolonged surgical time/blood loss/postoperative fever/dural tears/delayed wound healing) during primary surgery, as per available medical records. All returned to work with modifications to suit their surgery.
All patients (M:F = 4:1) resided in urban areas with no visits to rural areas. The average age was 55.2 years (45–61 years). All patients presented with infection at the operated level (L4-5 in four and L3-4 in one patient). None of the patients had wound dehiscence or pus discharge from the wound. There were no signs of extra spinal fungal or pyogenic infection. An attempt to isolate the organism by a CT-guided biopsy was made in all the patients by their respective primary surgeons, but it proved to be inconclusive.
All patients complained of severe disabling and progressive lumbar spasms. Two patients complained of radicular pain along with back spasm. All the patients had normal neurology except one who had developed right ankle dorsiflexor weakness (grade 3) and extensor hallusis longus weakness (grade 0) after primary surgery, which persisted till final follow-up. The average delay from the primary surgery to onset of pain was 6.4 weeks (4–10 weeks). The average delay from the onset of symptoms postprimary surgery to secondary surgery and a confirmatory diagnosis at the author’s institution was 7.6 weeks (5–12 weeks). Three of five patients were on empirical antibiotic therapy before presentation to the author’s institution. Two patients received empirical intravenous broad-spectrum antibiotics (injection Meropenem 1 gm thrice a day) for 2 weeks followed by 4 weeks of oral antibiotics (tab Levofloxacin 500 once a day), whereas one patient was on oral antibiotic therapy (tab Cefuroxime Axetil 500mg twice a day). Aspergillus Flavus was the most common organism isolated in our study (n = 3) followed by Candida Albicans (n = 1) and Penicllium Decumbens (n = 1).
There was a significant reduction in clinical outcome scores (VAS and ODI) and hematological parameters (ESR and CRP) [Table 2]. MRI at 3 months showed complete resolution of infection. Antifungal treatment was discontinued based on the clinical, hematological, and radiological resolution of infection [Figure 1].
|Table 2: Hematological and clinical outcomes before antifungal treatment and at the end of 3 months and final clinical outcome|
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|Figure 1: MRI scans before index surgery and at the end of 3 months. (A, B, C) Post-contrast mid-sagittal, T2-weighted mid-sagittal and axial images depicting L4/5 discitis and minimal paravertebral soft-tissue involvement. (D, E) T2-weighted mid-sagittal and axial image with complete radiological resolution at the end of 3 months|
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In one patient, after 3 months of normalcy, lumbar spasms recurred (ODI: 78 and VAS: 8). MRI showed discitis at the adjacent level (L3-4) with no disease activity at the primary level (L4-5) [Figure 2]. The fusion was extended to adjacent level. Oral voriconazole was recommenced for 12 weeks after confirmation of Aspergillus Flavus on culture growth. MRI was repeated after 3 months, which showed complete resolution of infection. The patient remained asymptomatic till the final follow-up (ODI: 20 and VAS: 2).
|Figure 2: Recurrence of discitis at adjacent segment L3/4 with fused L4/5 after 3 months of complete course of antifungal treatment. (A, B) Coronal and sagittal view of the CT scan showing fusion at L4-5 segment with end plate erosion of L3 and L4 vertebra. (C) Post-contrast MRI showing infection at adjacent level with no disease activity at the previous L4/5 level|
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| Discussion|| |
Fungal infections in immune-compromised hosts are cause of high mortality and morbidity. Surgical inoculation is being reported with increasing frequency to be the cause of infection even in immune-competent individuals.,
Most common organism producing infection belongs to Aspergillus and Candida species,, which is also evident in this series (Aspergillus 60% and Candida 20%). These organisms are ubiquitously found in soil, air, and water. Candida species are also known commensals of the human skin. The spores of these fungi can be present in the air for long durations. In a study done by Kelkar et al. in India, it was found that 26% of the operation theatres had fungal growth in their AC filters. Proper ventilation, humidity (<68%), and temperature control in the operating room is important not only for the comfort of surgical personnel and patients but also to help in preventing a milieu, which is conducive for growth and transmission of microorganisms. For most areas within health-care facilities, the designated comfort range is 30–60% relative humidity. Relative humidity levels more than 60%, in addition to being perceived as uncomfortable, promote fungal growth, and direct inoculation during surgery may take place. Studies by Garcia-Vidal et al.  and Zou et al. also suggest direct surgical inoculation to be the main cause of fungal infection.
Direct deep inoculation of infective organisms within the disc space permits their proliferation. Broad-spectrum antibiotics suppress local bacterial flora. It is hypothesized that surgery is the most potent activator of cortisol and ACTH secretion. Accumulation of macrophages and neutrophils at the site of inflammation is inhibited by cortisol, thereby interfering with the immune-response (Locus Minoris Resistentiae).,
Fungal growth has a predisposition for acidic pH. The Sobouraud Dextrose Agar used in fungal culture examination is maintained at an acidic pH of around 5.6 so as to allow fungal colony growth. The degenerative changes in the intervertebral disc initiate and propagate a cascade of events, leading to an acidic pH and cell death. We hypothesize that a degenerative disc with an acidic pH may prove conducive for fungal growth after a direct inoculation in an immune-competent host.
Sterilization of non-autoclavable instruments is a pertinent issue. Five steps of sterilization (clean–disinfect–rinse with distilled water–dry–store) should be strictly adhered in order to prevent recontamination of endoscopes with rinse water. Hydrogen peroxide, plasma gas sterilization and ethylene oxide (ETO) are an effective method for endoscopic sterilization. Plasma sterilization requires a special unit and plastic for packaging making it an expensive sterilization method., To the author’s best knowledge, in absence of plasma gas and ETO sterilization at many small centers, glutaraldehyde is used as the primary method of disinfection. All heat-sensitive endoscopes are subjected to a high level of disinfection with glutaraldehyde after every use. Activated alkaline solutions (pH 7.5–8.5) are sporicidal with a shelf life of 2 weeks. For sterilization with glutaraldehyde 10–12 h of soaking is required. A strict vigilance and periodic monitoring should be done for efficient functioning of glutaraldehyde as a high level disinfectant. Sabnis et al. in his study on sterilization of endoscopes reported that the way glutaraldehyde is used in many centers only disinfects but does not sterilize. All five cases reported in our study had undergone a primary coincidental minimal access surgery.
It takes a high index of suspicion to request for fungal culture in a postoperative infection unless a protocol is made to screen for all organisms. Patients are treated with empirical antibiotics allowing fungal infection to flourish, and a delay in diagnosis. Three of five patients in our study were on empirical antibiotic therapy. We presume this to be the main reason for delayed presentation at our institution. The average delay in onset of symptoms from primary surgery (6.4 weeks) and the average delay from onset of symptoms to a confirmatory diagnosis was 7.3 weeks. This was also observed by Gerometta et al. where the average delay was 6 weeks.
There are no specific guidelines for antifungal therapy in postoperative fungal discitis in “immune-competent” patient. There is no consensus whether conservative trial with medical management vis-à-vis surgical intervention offers better outcome. Zou et al. in their study observed a favorable outcome after a long-term antifungal treatment (6–12 months), where they regarded radiological fusion as resolution. Ganesh et al. in his literature review has acknowledged that patients treated surgically seems to have a possible advantage. Zussman et al. in his study concluded that combined surgical and medical management is preferable to isolated treatments. Discrepancy regarding the choice of surgical procedure also exist with divided views over debridement, posterolateral fusion and instrumented interbody fusion.,, The chief surgeon’s protocol in discitis is thorough debridement and to stabilize the subsequent defect by an interbody fusion. In our routine practice, PEEK cages are preferred for lumbar interbody fusions because of their modulus of elasticity closer to bone and stress shielding. Titanium cages have shown their efficacy in pyogenic discitis with less bacterial adherence but their advantage in fungal discitis has not been studied. Surgery is not advocated in every case of fungal discitis. The decision for surgical intervention by the author was based on the rationale that all the patients had a previous failed biopsy, delayed presentation, and disabling axial pain (ODI: 78.8 and VAS: 8.2). The surgery provided rapid alleviation of pain, definitive samples for biopsy, and reduced microbial load. However, we believe a major portion of the patients could have been conservatively managed if early biopsy proven diagnosis was achieved. The antifungal treatment, in correspondence with infectious disease specialist, was determined based on the organism and culture sensitivity. The antifungal treatment was stopped after clinical, hematological, and radiological demonstrable resolution of infection which was at 3 months. A combined surgical and medical treatment was successful in achieving favorable results in a shorter duration.
Recurrence of fungal infection is a matter of concern. Ganesh et al. and Wu et al. in their studies have reported a recurrence rate of 7.4% and 33.3%, respectively. One of five patients in our study had developed reactivation of fungal infection at the adjacent level after a remission period of 3 months. MRI scans did not show any signs of infection at the previously operated level. There was appreciable adjacent level (L3-4) disc space involvement with corresponding endplate destruction. A thorough debridement was carried out with extension of the stabilization. Intraoperative samples reconfirmed the infective organism to be similar as previously cultured and oral voriconazole was recommenced. At the end of 3 months, there was no radiological, hematological and clinical evidence of infection. Currently the patient is symptom free and the infection did not recur till date. In absence of standardized protocols, longer term follow-ups are required for any signs of reactivation of infection.
| Conclusion|| |
Emergence of fungal spondylodiscitis in immune-competent patients is a matter of concern and needs to be properly addressed. In routine circumstances, empirical use of broad-spectrum antibiotics without a conclusive biopsy should be discouraged. A protocol should be adopted where fungal infections are also screened along with pyogenic and mycobacterial infections. Operating room standards and protocols for instrument sterility should be strictly adhered to and periodically monitored. The termination of antifungal treatment should be done once complete clinical, hematological, and radiological resolution of infection is achieved and the patients should be serially followed up for long durations.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]