Conservative treatment may be still considered a viable therapeutic option for patients with spontaneous non-specific pyogenic spondylodiscitis. A retrospective audit study of 47 patients

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RESEARCH ARTICLE

Hippokratia 2023, 27(3): 106-111

Papavasiliou K1, Panagiotidou S1, Kakoulidis P1, Domashenko P1, Kenanidis E1, Bintoudi A2, Arvaniti K3, Potoupnis M1, Sarris I1, Tsiridis E1
13rd Academic Orthopedic Department, Aristotle University School of Medicine, Thessaloniki, Greece
2Department of Radiology, Papageorgiou General Hospital, Thessaloniki, Greece
3Critical Care Department, Papageorgiou General Hospital, Thessaloniki, Greece

Abstract

Background: Spontaneous non-specific pyogenic spondylodiscitis (SNPS) is a rare medical condition, whose optimal treatment remains controversial. We evaluated the multidisciplinary protocol implemented at our department for the conservative treatment of patients with SNPS.

Methods: Patients with lumbar or thoracic SNPS, whose treatment was initiated conservatively and had at least six months of follow-up, were enrolled in this retrospective audit study. Patients with specific, postoperative, or iatrogenic spondylodiscitis or necessitating immediate operative treatment were excluded. The location of the infection, initial symptoms, co-morbidities, pathogens, duration of antibiotic treatment, hospitalization and follow-up, and outcome were retrieved. The visual analogue scale (VAS) score was used to register pain improvement after treatment.

Results: Between January 2011 and December 2021, forty-seven patients (male: 26, mean age: 68.5 years) with SNPS (lumbar: 29, thoracic: 18) were hospitalized. The main co-morbidity was diabetes mellitus (23 patients). Pain was the predominant (46 patients), and fever was the second most common (19 patients) symptom. The most frequent causative microorganism was staphylococcus aureus (29 patients); no pathogen was identified in ten patients. The mean hospitalization duration for patients completing their conservative treatment (43/47) was 27 (range: 22-41) days. They received antibiotics for a mean period of 23 days intravenously (range: 21-29), 23.8 days per os (range: 21-35), and 46.8 days in total (range: 42-63). Conservative treatment was discontinued in two females. Two male patients died due to septic shock. The mean follow-up was 11.5 months (range: 6-15). During follow-up, no one developed any neurologic deficit and/or recurrence. There was a significant improvement in the mean VAS, from 8.3 ± 0.8 pre-treatment to 1.6 ± 0.5 at the latest follow-up (p <0.001).

Conclusions: Although treatment is gradually shifting towards surgical intervention, conservative therapeutic management of SNPS patients with antibiotic administration, bed rest, and careful mobilization remains a viable and efficacious option. HIPPOKRATIA 2023, 27 (2):106-111.

Keywords: Spontaneous non-specific pyogenic spondylodiscitis, spondylodiscitis, spinal infection, infection, visual analogue scale, conservative treatment

Cooresponding author: Papavasiliou Kyriakos, 3rd Academic Orthopedic Department, Aristotle University School of Medicine, Papageorgiou General Hospital of Thessaloniki, Ring Road west, 564 03 Nea Efkarpia, Thessaloniki, Greece, tel.: +306944531188, e-mail: papavasiliou.kyriakos@gmail.com

Introduction

Spontaneous non-specific pyogenic spondylodiscitis (SNPS) is a relatively rare medical condition, usually affecting elderly men and patients with diabetes mellitus and impaired immunocompetence1. Being more often the result of hematogenous spread1,2, it may be associated with increased morbidity and long-term severe sequelae, especially in cases of delayed diagnosis and/or inadequate treatment3.

The treatment of SNPS remains controversial. Several studies favor a more “aggressive” primary surgical approach4,5, involving cord decompression, debridement of infected tissues, and spinal stabilization6. On the other hand, conservative therapy is still considered by many to be a viable therapeutic modality7-9. The latter mainly consists of administering microorganism-specific antibiotics for six to twelve weeks, while critical-ill and septic patients are immediately administered with broad-spectrum antibiotics10. Bracing is also used to improve pain and prevent spinal deformity10.

The aim of the current study was to evaluate the efficacy and overall safety of the multidisciplinary diagnostic and therapeutic protocol implemented at our tertiary orthopedic department for the conservative treatment of patients with SNPS. Our hypothesis was that the proposed algorithm shown in Figure 1 is effective for the conservative treatment of SNPS.

Figure 1: Algorithm depicting the multidisciplinary approach to the management (diagnosis and treatment) of a patient suspected of having spontaneous non-specific pyogenic spondylodiscitis, which is followed at our institution.
MRSA: Methicillin resistant staphylococcus aureus, MRI: magnetic resonance imaging, ESR: erythrocyte sedimentation rate, CRP: Creacting protein, IV: intravenous, PO: per os.

Materials and Methods

Study design

We conducted a retrospective audit study in accordance with the World Medical Association’s declaration of Helsinki. Due to the study’s design as a retrospective clinical audit, ethical approval was not deemed necessary and thus not obtained; however, all patients received the standards of care according to institutional approved protocols during their hospitalization. Informed consent was obtained from all recruited patients participating in the analysis. In two cases, informed consent was provided by the patient’s relatives. The patients’ files and the medical notes regarding all patients suffering from SNPS treated at our department were retrieved and reviewed.

Participants

We included in the study i) all adult and pediatric patients with SNPS of the lumbar or thoracic spine, ii) who had adhered to the diagnostic workup and therapeutic protocol of our department, and whose treatment was initiated conservatively, iii) and were followed-up for at least six months after discharge. We excluded from the study i) patients with postoperative or iatrogenic spondylodiscitis, ii) patients with specific spondylodiscitis, and iii) patients necessitating immediate operative treatment.

Variables

We retrieved each patient’s demographic data, the location of the infection, the existing symptoms upon initial evaluation, the co-morbidities, the responsible pathogen (if identified), the duration of antibiotic treatment [intravenously (IV) and per os], the final outcome, and the duration of hospitalization and follow-up.

Treatment protocol

Per our protocol (Figure 1), any patient presenting with a history of non-traumatic, chronic spinal pain (of more than eight weeks duration) and either three or more yellow flags or one or more red flag(s) is suspected of suffering from SNPS (Figure 2), thus is promptly admitted to the hospital on an emergency basis. Following admission, each case is presented and discussed in the multidisciplinary infections meetings composed of an infectious disease specialist, a radiologist, and an orthopaedic surgeon. Patients are strongly advised to stay bedridden and undergo a simple radiographic examination and a contrast-enhanced (unless contra-indicated) magnetic resonance imaging (MRI) scan of both the thoracic and lumbar spine. Routine blood work tests combined with erythrocyte sedimentation rate (ESR) and C-reacting protein (CRP) are also performed. Once the diagnosis of SNPS has been confirmed (based on the MRI findings and further supported by an elevation of the ESR, and/or CRP, and/or white cell count), the patient undergoes at least three blood cultures. In each case, at least two sets of adequately filled blood cultures (aerobic and anaerobic bottles) are obtained, not necessarily in the event of a fever spike. Blood cultures are drawn at 24-hour time intervals, and one is consistently scheduled on the day the patient undergoes computed tomography (CT)-guided percutaneous needle biopsy. If a patient is on renal dialysis, at least one set of “twin” blood cultures (from the central venous catheter and a peripheral vein) is drawn. Further to all the above investigations, cardiac ultrasound is also performed to screen for the particularly serious infective endocarditis. Methicillin-resistant staphylococcus aureus (MRSA) screening swabs are also taken.

Figure 2: The yellow and red flags system followed at our institution, which is used during the evaluation of a patient suspected of having spontaneous non-specific pyogenic spondylodiscitis.

Patients with SNPS without a neurologic deficit and signs of spinal instability are treated with IV-administered antibiotics for at least three weeks. The selection of antibiotics is customized for each patient, based on identifying the responsible pathogen and all available clinical data, and is discussed during the multidisciplinary infections meeting. Probabilistic antibiotic therapy can also be considered when a pathogen cannot be identified and usually includes ciprofloxacin and clindamycin, combined in some cases with amoxicillin and clavulanic acid. Failure to respond to the antibiotic treatment (manifested by deterioration or not amelioration of symptoms and/or ESR and/or CRP, development of neurologic complication, and/or spinal instability) necessitates operative treatment. If a patient responds favorably, he/she is carefully mobilized utilizing a suitable brace. Following discharge, antibiotic treatment is continued per os for at least another three weeks. The brace is removed three months after the beginning of IV treatment. The patient is followed (clinical evaluation, routine blood workout, ESR, and CRP) at the outpatient clinic every month for the first six months and then every three months for another semester.

Statistical analysis

Data was analyzed using IBM SPSS Statistics for Windows, Version 25.0 (IBM Corp., Armonk, NY, USA). Standard descriptive statistics were performed. We assessed the normality of data with the Kolmogorov-Smirnov and Shapiro-Wilk tests.  Continuous variables are presented as mean differences ± standard deviations, while the confidence interval (CI) is set at 95 %. We utilized the Wilcoxon Signed Rank test to compare pre- and post-treatment clinical scores. A p value of less than 0.05 is considered as statistically significant. 

Results

Baseline characteristics

Between January 2011 and December 2021, forty-seven patients (male 26, female 21) with SNPS were admitted to the academic orthopedic department of Papageorgiou General Hospital. In 29 patients, the infection was located at the lumbar spine; in the remaining 18 patients, it was located in the thoracic spine. Their mean age was 68.5 (range 15-86) years. The main co-morbidity was diabetes mellitus (23 patients) (Table 1). Pain was the predominant (46 patients), and fever was the second most common symptom (19 patients) (Table 2). The leading causative microorganism was staphylococcus aureus (29 patients), while MRSA was identified in two patients. In ten patients, no pathogen was identified, and the diagnosis of SNPS was based on the MRI findings (whenever required, consecutive MRI scans were performed) and laboratory results (Table 3).

Outcomes

The mean duration of hospitalization for all patients (43) who completed their treatment conservatively was 27 (range 22-41) days. These patients received antibiotics for a mean period of 23 (range 21-29) days IV, per os for 23.8 (range 21-35) days, and in total for 46.8 (range 42-63) days. Conservative treatment was discontinued in two cases (both females) after 10 and 12 days of probabilistic treatment, respectively. In one patient, symptoms and laboratory blood tests deteriorated despite antibiotic treatment, and another developed progressive paraplegia. Both underwent successful operative treatment and were eventually discharged. Two male patients (a 78-years-old under dialysis with an MRSA infection and an 81-years-old with a history of cancer and a non-identified pathogen) died due to septic shock; both were non-fit to undergo an operation. Forty-three patients were discharged. Their mean follow-up period was 11.8 (range 6-15) months. There was a significant improvement in the mean Visual Analogue Scale (VAS) score from 8.3 ± 0.8 pre-treatment to 1.6 ± 0.5 at the latest follow-up (p <0.001). During their follow-up visits, none developed any neurologic deficit and/or had any signs and laboratory tests suggesting a recurrence. 

Discussion

We audited the efficacy and safety of the multidisciplinary diagnostic and therapeutic protocol implemented at our tertiary orthopaedic department for the conservative treatment of patients with SNPS. Although treatment seems to be gradually shifting towards surgical intervention, conservative treatment with prolonged IV antibiotic administration, bed rest, and careful mobilization, as illustrated by this study’s results as well, remains still a viable and efficacious option.

There are several limitations in this study. A significant limitation is that the study is retrospective, and selection bias is present. As a result, we had to rely on uncontrolled record-keeping to evaluate the patients’ outcomes. Another limitation was the lack of a comparative group of operatively treated patients, which would have undoubtedly allowed a direct comparison between the two treatment methods. However, this task would have been challenging, if not impossible, due to the scarcity of the disease and the non-homogeneity of the patients with SNPS. Another limitation was that antibiotic treatment was customized for each patient since several factors (age, pathogen, overall medical condition, and response to previous treatment) had to be considered. Although not necessarily a therapeutic limitation, it prevents homogenizing patients into groups to compare different antibiotic regimens. Due to all the above factors, it is almost impossible to conduct large, prospective randomized studies comparing conservative with surgical results. Further, since the use of MRI scans for the follow-up imaging of patients with SNPS remains controversial and was not introduced in everyday practice until recently, we did not implement and evaluate this modality in our study11.

Spontaneous non-specific pyogenous spondylodiscitis is a relatively rare disease1,9,12-14. An alarming increase in the number of patients with SNPS, manifested during the last two decades in Europe4,15, can be attributed to the aging of the population, the exposure of more patients to an ever-increasing number of interventional diagnostic and therapeutic procedures, the difficult access to healthcare systems for patients with low economic and social status, the increased number of intravenous drug users, and the higher efficacy in the diagnosis of the condition with the use of the MRI scan5,9,16,17. The demographic data of our patients, are in agreement with these findings.

The typical patient with SNPS reports a gradual onset of symptoms, which are non-disease specific, and several weeks with symptoms before seeking medical advice. As in the majority of the reported cases1,5, also in our study, the main symptom of almost all patients was spinal pain. The patient could easily pinpoint the tenderness spot. The pain increased in severity on palpation and spinal movements; in some cases, it radiated. Fever was also apparent in 40 % of our patients. The gradual onset and the initially mild and non-specific symptoms usually delay the diagnosis, rendering adequate treatment challenging and potentially augmenting the possibility for increased mortality and morbidity rates and long-term severe sequelae1,3,5. The mortality rate in this series (4 %) is similar to the ones reported by the literature9.

An MRI scan, combined with blood work tests that include whole blood cell count, ESR, and CRP, usually sets the diagnosis. MRI scan is considered the gold standard imaging modality in patients with SNPS18, since it was found to have as high as 96 % sensitivity, specificity of 92 %, and accuracy of 94 %1. Our study also confirmed these results.

CT-scan-guided biopsy plays a pivotal role in diagnosing the microorganism responsible for the infection19,20. As in the majority of reported cases1,7,21, in our study, staphylococcus aureus was the most frequently identified pathogen, followed by gram-negative, and anaerobic bacteria. Infections caused by MRSA are relatively uncommon, albeit challenging to treat1.

SNPS used to be a disease treated in most cases conservatively. Prolonged IV and per os antibiotic treatment was combined with bed rest and the subsequent careful mobilization of patients with adequate bracing1,7. Literature suggests intravenous culture-directed antibiotics for four to six weeks and oral administration totaling six to twelve weeks22. The best evidence available comes from Bernard et al23 who conducted a randomized control trial that included 359 patients and showed no differences in clinical cure or adverse events between six and twelve weeks of antibiotic therapy. However, there still needs to be a consensus regarding the duration and route of antibiotic administration. Operative treatment was implemented only in patients with mechanical instability, spinal deformity, and neurologic deficit and in patients non-responding to conservative treatment since it was accompanied by an increased number of complications, morbidity, and mortality rates7. However, treatment has gradually shifted towards surgical intervention, mainly due to the new materials used in spinal surgery and the less invasive surgical techniques6,7,24,25. As a result, many authors advocate for immediate operative treatment for all patients, regardless of whether or not neurologic deficits coexist. They associate operative treatment with diminished hospitalization period, better pathogen identification rates, quicker mobilization, and better overall results3,5,7,26,27.

On the other hand, several studies continue favor conservative treatment, even though the necessity of surgical intervention in selected cases is recognized1,5,8. In our study, most patients (93 %) completed their treatment uneventfully, had no recurrence, nor develop any mid-term complications. Four patients, however, required surgical intervention. Eventually, the optimal treatment for patients with SNPS can be secured solely if all critical decisions are taken during multidisciplinary infection meetings12,21.

Proper and prompt diagnosis and adequate treatment may be a challenging task when dealing with patients with SNPS. Although treatment is gradually shifting towards surgical intervention, conservative treatment with prolonged antibiotic administration, bed rest, and careful mobilization of the patients remains still a viable, safe, and efficacious option. Surgical treatment is mandatory when conservative treatment fails. Careful physical examination, adequate imaging, laboratory studies, and -most importantly- close monitoring and early identification of signs of spinal instability, neurologic deficit, and/or irresponsiveness to treatment, guarantee the best patient results. Ideally, the optimal treatment plan for each individual should be discussed and decided during the multidisciplinary infections meeting. 

Conflict of Interest Statement

The authors state no conflicts of interest. 

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