ORIGINAL RESEARCH article

Front. Surg., 09 January 2024

Sec. Neurosurgery

Volume 10 - 2023 | https://doi.org/10.3389/fsurg.2023.1333764

The impact of concomitant infective endocarditis in patients with spondylodiscitis and isolated spinal epidural empyema and the diagnostic accuracy of the modified duke criteria

  • 1. Department of Neurosurgery, Division of Spine Surgery, Technische Universität Dresden, Faculty of Medicine, and University Hospital Carl Gustav Carus, Dresden, Germany

  • 2. Department of Neurology, Technische Universität Dresden, Faculty of Medicine, and University Hospital Carl Gustav Carus, Dresden, Germany

  • 3. Department of Cardiology and Angiology, Bergmannsheil University Hospitals, Ruhr University Bochum, Bochum, Germany

  • 4. Faculty of Medicine, and University Hospital Carl Gustav Carus, Institute for Microbiology and Virology, Technische Universität Dresden, Dresden, Germany

  • 5. Department of Anesthesiology and Intensive Care Medicine, Technische Universität Dresden, Faculty of Medicine, and University Hospital Carl Gustav Carus, Dresden, Germany

Abstract

Background:

The co-occurrence of infective endocarditis (IE) and primary spinal infections (PSI) like spondylodiscitis (SD) and isolated spinal epidural empyema (ISEE) has been reported in up to 30% of cases and represents a life-threatening infection that requires multidisciplinary management to be successful. Therefore, we aimed to characterize the clinical phenotypes of PSI patients with concomitant IE and furthermore to assess the accuracy of the modified Duke criteria in this specific population.

Methods:

We conducted a retrospective cohort study in consecutive SD and ISEE patients treated surgically at our University Spine Center between 2002 and 2022 who have undergone detailed phenotyping comprising demographic, clinical, imaging, laboratory, and microbiologic assessment. Comparisons were performed between PSI patients with IE (PSICIE) and without IE (PSIWIE) to identify essential differences.

Results:

Methicillin-susceptible Staphylococcus aureus (MSSA) was the most common causative pathogen in PSICIE group (13 patients, 54.2%) and aortic valve IE was the most common type of IE (12 patients, 50%), followed by mitral valve IE (5 patients, 20.8%). Hepatic cirrhosis (p < 0.011; OR: 4.383; 95% CI: 1.405–13.671), septic embolism (p < 0.005; OR: 4.387; 95% CI: 1.555–12.380), and infection with Streptococcus spp. and Enterococcus spp. (p < 0.003; OR: 13.830; 95% CI: 2.454–77.929) were identified as significant independent risk factors for the co-occurrence of IE and PSI in our cohort. The modified Duke criteria demonstrated a sensitivity of 100% and a specificity of 66.7% for the detection of IE in PSI patients. Pathogens were detected more frequently via blood cultures in the PSICIE group than in the PSIWIE group (PSICIE: 23, 95.8% vs. PSIWIE: 88, 62.4%, p < 0.001). Hepatic cirrhosis (PSICIE: 10, 41.7% vs. PSIWIE: 33, 21.6%, p = 0.042), pleural abscess (PSICIE: 9, 37.5% vs. PSIWIE: 25, 16.3%, p = 0.024), sepsis (PSICIE: 20, 83.3% vs. PSIWIE: 67, 43.8%, p < 0.001), septic embolism (PSICIE: 16/23, 69.6% vs. PSIWIE: 37/134, 27. 6%, p < 0.001) and meningism (PSICIE: 8/23, 34.8% vs. PSIWIE: 21/152, 13.8%, p = 0.030) occurred more frequently in PSICIE than in PSIWIE patients. PSICIE patients received longer intravenous antibiotic therapy (PSICIE: 6 [4–7] w vs. PSIWIE: 4 [2.5–6] w, p < 0.001) and prolonged total antibiotic therapy overall (PSICIE: 11 [7.75–12] w vs. PSIWIE: 8 [6–12] w, p = 0.014). PSICIE patients spent more time in the hospital than PSIWIE (PSICIE: 43.5 [33.5–53.5] days vs. PSIWIE: 31 [22–44] days, p = 0.003).

Conclusions:

We report distinct clinical, radiological, and microbiological phenotypes in PSICIE and PSIWIE patients and further demonstrate the diagnostic accuracy of the modified Duke criteria in patients with PSI and concomitant IE. In the high-risk population of PSI patients, the modified Duke criteria might benefit from amending pleural abscess, meningism, and sepsis as minor criteria and hepatic cirrhosis as major criterion.

1 Introduction

Infective endocarditis (IE) refers to infection of a native or prosthetic heart valve, the endocardial surface, or an implanted cardiac instrument (). Primary spinal infection (PSI) manifests mainly as spondylodiscitis (SD) or isolated spinal epidural empyema (ISEE), with SD resulting predominantly from hematogenous pathogen dissemination ().

The co-occurrence of IE and SD has been reported up to 30% of cases (), with endocarditis being more common in SD than in ISEE (). Treatment of such life-threatening infections requires a multidisciplinary approach to achieve success.

In a patient with known IE and a new onset of back pain, imaging must be performed to rule out SD (, ). Similarly, any patient with SD should have a transthoracic echocardiogram (TTE) and if necessary, a transesophageal echocardiography (TEE) to exclude IE, especially if the patient has a proven gram-positive bacterium (GPB) or a heart valve replacement. The modified Duke criteria have been developed for all types of IE, although the accuracy in SD and ISEE patients has not yet been studied.

Behmanesh et al. demonstrated a tenfold higher rate of diagnosed IE after routine use of TEE in patients with known SD (). TTE is recommended as first-line imaging in all patients with abnormal blood cultures, a new heart murmur, or suspected IE; due to sensitivity TEE should be performed in case of negative TTE but high suspicion of IE, equivocal TTE, prosthetic valves, cardiac devices, and positive TTE to detect other complications (). Some authors suggest to perform TEE initially in patients with suspected IE who have an intermediate to high pretest probability of IE, including those with prosthetic heart valves, blood cultures growing Staphylococci, or an intracardiac device (), although TTE may be equivalent and sometimes superior to TEE in the evaluation of the anterior cardiac regions, the cardiac apex, and the tricuspid valve ().

Maintaining TTE as the first imaging examination should therefore always be considered depending on the clinical situation mentioned above, and TEE examination should then follow immediately regardless of the TTE findings due to the high prevalence of IE in SD (). Cardiac computer tomography (CT) and 18F-FDG PET/CT represent additional options in the diagnostic algorithm (, , ).

The diagnosis of IE is based on the Duke criteria, described originally in 1994 and modified in 2000 (, ). Despite the widespread use of these criteria for the diagnosis of IE, there are significant limitations, and a substantial proportion of patients are classified as “possible IE” ().

Previous studies have suggested that the time to diagnosis has a substantial impact on prognosis and mortality in PSI and IE and that the mortality rate is higher in patients with concomitant PSI and IE compared with PSI patients without IE (). Baseline and risk factors, clinical course, causative pathogens, and surgical and anti-infective strategies for PSI patients with IE are poorly defined (, ).

Currently, there are several case reports of percutaneous mechanical debulking of vegetations or cysts in patients with IE or other cardiac infections using an AngioVac system (, ).

The accuracy of the modified Duke criteria in this subpopulation is unknown and treatment guidelines for this challenging subgroup of patients at risk are lacking to date. Therefore, we aimed to analyze the clinical and microbiological phenotype of patients with PSI and IE and we furthermore sought to identify risk factors for the co-occurrence of IE and PSI. Finally, we investigated the diagnostic accuracy of the modified Duke criteria in this specific subpopulation.

2 Materials and methods

2.1 Study design

We conducted a retrospective observational study to evaluate patients diagnosed with PSI with/without IE who underwent surgery at our University Neurosurgical Spine Centre between 2002 and 2022.

A total of 228 patients were identified. Fifty-one patients had to be excluded based on any of the following criteria:

  • -

    an echocardiographic assessment was not performed or documented (n = 31)

  • -

    only conservative treatment (n = 8)

  • -

    intradural infection (n = 12)

One hundred seventy-seven patients with primary SD and ISEE were included in the study. They underwent echocardiography, of whom 161 were diagnosed with pyogenic spinal infection and 4 with non-pyogenic infection, whereas no pathogen was detected in 12 patients (

Figure 1

).

Figure 1

2.2 Patient data

The study was conducted in accordance with the Helsinki Declaration. A positive vote of the responsible local ethics committee (Reference number BO-EK-17012022) has been obtained and an informed consent was waived. After case identification, patient data were extracted by reviewing electronic medical records using the ORBIS system (ORBIS, Dedalus, Bonn, Germany). Radiological data, including gadolinium contrast-enhancing magnetic resonance imaging (MRI), CT and/or x-ray were available for review in all cases.

Data collected included sex, age, type of PSI, causative pathogen, radiological findings on MRI and CT, and number of successful pathogen detections via blood cultures, intraoperative specimens, or CT-guided biopsies of the paravertebral psoas abscess. We also collected data on time passed to pathogen detection, type of antibiotic strategy, presence of psoas or pleural abscesses, spinal location of infection, time passed to surgery, use of intraoperative antibiotic irrigation, use of postoperative epidural suction-irrigation drainage, incidental dural tears, primary source of infection, surgical and antibiotic treatment, type of surgical procedure, risk factors (immunosuppression, diabetes mellitus, obesity, malignancy, liver cirrhosis, dialysis, stent or vascular prosthesis, artificial heart valve replacement, osteoporosis, rheumatoid arthritis or elevated rheumatoid factors, gout or elevated uric acid, chronic venous insufficiency, peripheral artery disease, and atrial fibrillation), disease-related complications (relapse rate, sepsis, septic embolism, meningism, success rate, reoperation due to surgical site infection, reoperation because of persistent empyema or spinal instability, disease-related mortality, hospitalization, and intensive care unit (ICU) stay), and classification according to the modified Duke criteria (definitive, possible, or rejected IE).

2.3 Clinical management

2.3.1 Clinical, microbiological, and radiological diagnostics

The diagnosis of SD or ISEE was performed on the basis of medical history, clinical examination, fever, laboratory values (leukocyte count, C-reactive protein (CrP), and procalcitonin), typical radiological findings on MRI and CT, and pathogen detection on blood cultures, intraoperative specimens, or CT-guided biopsies of the paravertebral psoas abscess.

TTE was performed in all patients and the modified Duke criteria were applied, whereas in patients with GPB, possible or definite IE, TEE was performed according to the modified Duke criteria.

At least two blood cultures were obtained, and empirical or targeted antibiotic therapy (EAT, TAT) was performed. Tissue samples obtained during open surgery and samples taken by CT-guided biopsies were used for microbiological and histopathological analysis.

The diagnosis of ISEE or SD was determined in our multidisciplinary spine conference or neurosurgical-neuroradiological conference, and therapy was decided in collaboration with infectiologists, if possible. We have established a multidisciplinary spine board that includes neuroradiologists, neurosurgeons, trauma surgeons, orthopedic surgeons, and infectiologists, when appropriate, to determine the best treatment strategy for patients.

2.3.2 Surgical and antibiotic management

Conservative treatment with intravenous antibiotics was usually the first-line of treatment, and surgical treatment was indicated in the absence of source control, epidural abscess, neurologic deficit, or spinal instability, with the type of surgical procedure determined in the multidisciplinary spine board or neurosurgical-neuroradiological conference.

ISEE patients underwent abscess evacuation with postoperative epidural suction-irrigation drainage or anterior cervical discectomy and fusion (ACDF) with abscess evacuation for abscesses ventral to the cervical spinal cord.

Patients with SD were treated with either abscess evacuation alone or one- or two-stage surgery. All patients with SD received a CT scan to assess bone structures and signs of instability. In case of biomechanical instability, patients underwent one-stage surgery for abscess evacuation and stabilization. Patients who initially had no instability and developed instability after abscess evacuation underwent two-stage surgery in terms of instrumentation. Surgical decision-making therefore depends on clinical experience and various defined radiological and clinical characteristics.

According to the clinical condition on admission and according to the recommendations of the local infectious diseases department, all patients were treated with either TAT or EAT strategy. However, it is important to note that most patients with EAT presented to us from peripheral hospitals and required immediate surgery; therefore, the number of EAT patients was high. EAT was changed to TAT after the causative pathogens were detected.

When surgical treatment was required in patients with proven concomitant endocarditis and PSI (SD or ISEE), abscess evacuation with placement of an epidural suction-irrigation drainage was performed in the first line if the patients had a stable cardiac state. In the case of spinal instability and a well-defined indication for instrumentation, we performed a single-stage surgery. In case of cardiac decompensation, cardiologic and cardiosurgical evaluation was performed first, with medical treatment and surgical sanitation of endocarditis, if necessary, followed by re-evaluation of possible spinal surgery.

Intravenous antibiotic treatment was administered to ISEE patients for approximately 2 weeks and additional oral antibiotic treatment for 2 to 4 weeks, whereas SD patients received intravenous antibiotic therapy for approximately 4 to 6 weeks and additional oral antibiotic therapy for 6 to 8 weeks. Clinical and radiological follow-up was performed in all patients who complied with our recommendation at 3, 6, and 12 months after hospital discharge.

2.4 Case illustration of infective endocarditis

We present a 66-year-old male patient with infective endocarditis of the aortic valve who had an abscess at the aortic root and endocarditis of the mitral valve with perforation of the posterior mitral leaflet (PML). The patient has known gout and underwent pancreatectomy, splenectomy, subtotal gastrectomy, and subtotal colectomy due to a neuroendocrine tumor in the left upper abdomen with liver metastases. He had a port implanted in the left subclavian vein, but 2 months later he developed sepsis due to a port infection caused by Staphylococcus epidermidis. The patient had paraparesis, and MRI showed extensive spondylodiscitis with an epidural abscess ventrodorsally at the level of L2 to S2. Staphylococcus epidermidis was both times detected via blood culture and intraoperatively when an epidural abscess was evacuated, an infected port was removed, and a pleural drainage was inserted for several pleural abscesses. The abscess was drained via an interlaminar approach at the level of L3/4 on the right, and an epidural suction-irrigation drainage was inserted. The patient was treated locally and systematically with antibiotics and could be transferred for rehabilitation. He was first treated with vancomycin intravenously for 3 weeks and then with linezolid and daptomycin intravenously for 5 weeks because of impaired renal function before being discharged home. Follow-up after completion of antibiotic treatment was unremarkable (TTE, MRI of spine and CT of thorax and abdomen, infectious parameters). After about 6 months, the patient's general condition deteriorated and he developed dyspnea, cough, fever, palpitations, and weight loss. He was admitted to the emergency room, where severe sepsis was again evident. MRI of the spine performed showed no relevant new abscess or discitis, but TEE showed a new-onset infective double-valve endocarditis. Blood cultures again showed multiple Staphylococcus epidermidis and Staphylococcus caprae. However, the CT of the thorax showed no abscesses in the lungs. Treatment with daptomycin was resumed, and MRI examination of the neurocranium due to seizures showed multiple septic emboli. From a cardiac surgical point, the indication for surgical repair with valve replacement was given for aortic and mitral insufficiency III°. Aortic and mitral valve replacement was performed by xenotransplantation of 21 and 27 mm SJM Epic (Supra) and stabilization of the aortic annulus by a tubular prosthetic ring (Calamari) and then the patient was discharged to home. Antibiotic therapy with daptomycin was continued for a further 4 weeks. A new port was implanted and a urinary tract infection and pneumonia occurred in the course of the treatment, which was followed by renewed antibiotic therapy with Piperacillin/tazobactam. Another port explantation was performed and a shaldon catheter was inserted for acute renal failure. A hematoma formed during bleeding from the superficial femoral artery, subsequently the hematoma was surgically evacuated. The antibiotics were stopped after 2 weeks. The acute renal failure regressed and the patient could be mobilized to the ward floor. The TEE check revealed paraprosthetic aortic valve insufficiency. Cardiac surgery was therefore recommended. The patient and his relatives decided against surgery and renewed antibiotic treatment. The patient was discharged home with a palliative concept and died a few weeks later (Figure 2).

Figure 2

2.5 Statistical analysis

The SPSS software package (SPSS Statistics 28, IBM, Armonk, New York, USA) was used for all statistical analyses. Descriptive statistics were used, and categorical variables were compared between PSICIE and PSIWIE using Fisher's exact tests or chi-square tests. Numeric variables were compared with Mann-Whitney U tests. All statistical tests were two-sided tests, and a p-value of p < 0.05 was considered statistically significant. Univariate and multivariate analyses were conducted to identify independent risk factors. Sensitivity = (true positives) / (true positives + false negatives) and specificity = (true negatives) / (true Negatives + false positives) ().

3 Results

3.1 Demographic data and patient characteristics

We included 177 patients (men: 116, 65.5%) with 90 patients over 65 years (50.8%), of whom 125 presented with SD (70.6%) and 52 with ISEE (29.4%) (Table 1). PSI was identified in 161 patients (91.0%) and non-pyogenic spinal infection in 4 patients (2.2%), whereas the causative pathogen could not be detected in 12 patients (6.8%). Methicillin-susceptible Staphylococcus aureus (MSSA) was isolated in 53.4% (86/161), Streptococcus spp. and Enterococcus spp. in 18.0% (29/161), Enterobacterales in 11.2% (18/161), and Coagulase-negative Staphylococci (CoNS) in 9.9% (16/161). GPB represented 86.3% of cases (139/161) and Gram-negative bacteria (GNB) 13.7% of cases (22/161).

Table 1

CharacteristicsN = 177Percentage
Baseline factors
Males11665.5%
Females6134.5%
Age > 659050.8%
Spondylodiscitis12570.6%
Isolated spinal epidural empyema5229.4%
Pathogen
Pyogenic spinal infection16191.0%
Non-pyogenic spinal infection42.2%
Known causative pathogens16593.2%
Unknown causative pathogens126.8%
MSSA86/16153.4%
Streptococcus spp. & Enterococcus spp.29/16118.0%
Enterobacterales18/16111.2%
CoNS16/1619.9%
Gram-positive bacteria139/16186.3%
Gram-negative bacteria22/16113.7%
Diagnostic and therapy
Surgery177100%
Blood cultures177100%
CT-guided biopsy of psoas abscess59/11053.6%
Detected via blood cultures111/16567.3%
Detected via intraoperative specimens137/16583.0%
Detected via CT-guided biopsy of psoas abscess35/5959.3%
EAT11665.5%
TAT6134.5%
Known primary infectious sources12771.8%
Paravertebral psoas abscess11062.1%
Pleural abscess3419.2%
CS4827.1%
TS7039.5%
LS12067.8%
Multiple localizations of spinal parts4927.7%
Time to surgery1 [1–4] d
Time to pathogen detection4 [3–6] d
Incidental dural tears2313.0%
Intraoperative antibiotic Irrigation14883.6%
Suction-irrigation drainage12168.4%
Only abscess evacuation7542.4%
One-staged surgery (evacuation and concomitant fixation)6838.4%
Two-staged surgery (evacuation followed by fixation)3419.2%
Intravenous antibiotic duration4 [3–6] w
Total antibiotic duration8 [6–12] w
Risk factors
Immunosuppression3117.5%
Diabetes mellitus6637.3%
Obesity (BMI > 30 kg/m2)5430.5%
Malignancy3419.2%
Hepatic cirrhosis4324.3%
Dialysis74%
Stent or vascular prosthesis158.5%
Artificial heart valve replacement126.8%
Osteoporosis77/16447.0%
Rheumatoid arthritis or increased rheumatic factors34/8739.1%
Gout or increased uric acid42/8748.3%
Chronic venous insufficiency52.8%
Peripheral artery disease105.6%
Atrial fibrillation4223.7%
Disease-related complications
Disease-related mortality95.1%
Relapse rate26/11622.4%
Sepsis8749.2%
Septic embolism elsewhere53/15733.8%
Meningism29/17516.6%
Infective endocarditis with vegetation in echocardiography2413.6%
Reoperation due surgical site infections2614.7%
Reoperation due to empyema persistence or instability4726.6%
Hospital stay33 [19–44] d
ICU stay4 [0–16] d
Modified Duke-criteria
Definitive IE based on modified Duke-criteria3218.1%
Possible IE based on modified Duke-criteria4324.3%
Rejected IE based on modified Duke-criteria10257.6%

Patient characteristics.

SD, spondylodiscitis;ISEE, isolated spinal epidural empyema; MSSA, methicillin-susceptible Staphylococcus aureus; CoNS, coagulase-negative Staphylococci; CT, computer tomography; EAT, empirical antibiotic therapy; TAT, targeted antibiotic therapy; CS, cervical spine; TS, thoracic spine; LS, lumbar spine; BMI, body mass index; ICU, intensive care unit; IE, infective endocarditis; d, days; w, weeks. Bold values are significant results (p < 0.05) as indicated in the methods.

Multiple blood cultures and intraoperative samples were taken from all patients, whereas 59 tappable patients (53.6%) out of 110 patients with paravertebral psoas abscess (62.1%) underwent CT-guided biopsy. Pathogens were detected in 67.3% via blood cultures (111/165), in 83.0% via intraoperative specimens (137/165), and in 59.3% via CT-guided biopsy of a paravertebral psoas abscess (35/59).

EAT was initially performed in 116 patients (65.5%) and later changed to TAT as soon as the underlying bacterial species was known, while 61 patients (34.5%) were treated directly with a TAT. The primary infectious sources were identified in 127 of the cases (71.8%). Pleural abscess occurred in 34 patients (19.2%).

The infection was located in the cervical spine in 48 patients (27.1%), in the thoracic spine in 70 patients (39.5%), and in the lumbar spine in 120 patients (67.8%), while 49 of these cases had multiple locations in the spinal parts (27.7%).

The time from diagnosis of infection on MRI to performing surgery was 1 [1–4] days (median [interquartile), whereas the time to pathogen detection was 4 [3–6] days. Incidental dural tears occurred in 23 patients (13.0%), 148 patients (83.6%) were irrigated intraoperatively with local antibiotic (gentamicin, vancomycin, or both), whereas 121 patients were treated with postoperatively epidural suction-irrigation drainage 121 (68.4%).

Abscess evacuation alone was performed in 75 patients (42.4%), whereas single-stage surgery (evacuation and concomitant fixation, 38.4%) was performed in 68 patients and two-stage surgery (evacuation followed by fixation, 19.2%) was achieved in 34 patients. Patients received intravenous antibiotics for approximately 4 [3–6] weeks and a total antibiotic duration of approximately 8 [6–12] weeks.

Among the co-morbidities, 31 patients had immunosuppression (17.5%), 66 patients had a medical history of diabetes mellitus (37.3%), 54 patients were overweight with body mass index (BMI) over 30 kg/m2 (30.5%), 34 patients had malignancy (19.2%), 43 patients suffered from liver cirrhosis (24.3%), 7 patients required dialysis (4.0%), 15 patients had a stent or vascular prosthesis (8.5%), 12 patients had an artificial heart valve replacement (6.8%), 77 of 164 patients were osteoporotic (47.0%), 34 of 87 patients suffered from rheumatoid arthritis or had elevated rheumatoid factors (39.1%), 42 of 87 patients had gout or elevated uric acid (48.3%), 5 patients showed chronic venous insufficiency (2.8%), 10 patients had peripheral artery disease (5.6%), and 42 patients had atrial fibrillation (23.7%).

A total of nine patients (5.1%) died from the diseases and their complications, and 26 of 116 patients (22.4%) relapsed. Sepsis was observed in 87 patients (49.2%), septic embolism in 53 of 157 patients (33.8%), meningism in 29 patients (16.6%), and infective endocarditis with vegetations on echocardiography in 24 patients (13.6%). Reoperation due to surgical site infection was performed in 26 patients (14.7%), and reoperation due to persistent empyema and spinal instability was reported in 47 patients (26.6%). Median hospital stay was 33 [19–44] days and length of stay in the intensive care unit (ICU) was 4 [0–16] days.

Using the modified Duke criteria, 32 patients (18.1%) were considered as definitive IE, 43 patients (24.3%) as possible IE, and 102 as rejected IE (57.6%).

3.2 PSICIE vs. PSIWIE

There were significantly more SD patients in the PSICIE group (n = 23, 95.8%) than ISEE patients (n = 1, 4.2%, p = 0.003). Gender, age, and microbial groups such as MSSA, Enterobacterales, and CoNS demonstrated no difference between the two groups. In contrary, the Streptococcus spp. & Enterococcus spp. subgroup occurred significantly more often in PSICIE (n = 8, 34.8%) than PSIWIE (n = 21, 15.2%, p = 0.037). The PSICIE group consisted only of GPB compared to the PSIWIE group (PSICIE: 23, 100.0% vs. PSIWIE: 116, 84.1%, p = 0.046) (Table 2).

Table 2

CharacteristicsPSICIEPSIWIEp-value
Baseline factors
Males19 (79.2%)97 (63.4%)0.168a
Females5 (20.8%)56 (36.6%)
Age > 6513 (54.2%)77 (50.3%)0.827a
Spondylodiscitis23 (95.8%)102 (66.7%)0.003a
Isolated spinal epidural empyema1 (4.2%)51 (33.3%)
Pathogen
Pyogenic spinal infection23 (95.8%)150 (98.0%)0.445a
Non-pyogenic spinal infection1 (4.2%)3 (2.0%)
MSSA13 (56.5%)73 (52.9%)0.824a
Streptococcus spp. & Enterococcus spp.8 (34.8%)21 (15.2%)0.037a
Enterobacterales0 (0.0%)18 (13.0%)0.078a
CoNS2 (8.7%)14 (10.1%)1.000a
Gram-positive bacteria23 (100.0%)116 (84.1%)0.046a
Gram-negative bacteria0 (0.0%)22 (15.9%)
Diagnostic and therapy
Detected via blood cultures23 (95.8%)88 (62.4%)<0.001a
Detected via intraoperative specimens18 (75%)119 (84.4%)0.251a
Detected via CT-guided biopsy of psoas abscess6/8 (75.0%)29/51 (56.9%)0.453a
EAT8 (33.3%)108 (70.6%)<0.001a
TAT16 (66.7%)45 (29.4%)
Polymicrobial infections1 (4.2%)7 (5.0%)1.000a
Paravertebral psoas abscess16 (66.7%)94 (61.4%)0.659a
CT-guided biopsy of psoas abscess8 (33.3%)54 (35.3%)1.000a
Pleural abscess9 (37.5%)25 (16.3%)0.024a
CS7 (29.2%)41 (26.8%)0.808a
TS10 (41.7%)60 (39.2%)0.826a
LS19 (79.2%)101 (66.0%)0.245a
Multiple localizations of spinal parts10 (41.7%)39 (25.5%)0.139a
Time to surgery2 [1–4] d2 [1–7] d0.624b
Time to pathogen detection3.5 [2–5] d5 [3–8.5] d0.054b
Incidental dural tears6 (25.0%)17 (11.1%)0.067a
Intraoperative antibiotic Irrigation19 (79.2%)129 (84.3%)0.554a
Suction-irrigation drainage17 (70.8%)104 (68.0%)1.000a
Only abscess evacuation9 (37.5%)66 (43.1%)0.662a
One-staged surgery (evacuation and concomitant fixation)11 (45.8%)57 (37.3%)0.500a
Two-staged surgery (evacuation followed by fixation)4 (16.7%)30 (19.6%)1.000a
Intravenous antibiotic duration6 [4–7] w4 [2.5–6] w<0.001b
Total antibiotic duration11 [7.75–12] w8 [6–12] w0.014b
Primary infectious sources
Skin infection6 (30.0%)25 (23.4%)0.231a
Foreign body associated infection7 (35.0%)16 (15.0%)
Epidural administration2 (10.0%)19 (17.8%)
Respiratory tract3 (15.0%)17 (15.9%)
Urinary tract0 (0.0%)11 (10.3%)
Gastrointestinal tract1 (5.0%)8 (7.5%)
Retropharyngeal and prevertebral infection0 (0.0%)6 (5.6%)
Odontogenic0 (0.0%)4 (3.7%)
Immunosuppression1 (5.0%)1 (0.9%)
Risk factors
Immunosuppression5 (20.8%)26 (17.0%)0.577a
Diabetes mellitus9 (37.5%)57 (37.3%)1.000a
Obesity (BMI > 30 kg/m2)5 (20.8%)49 (32.0%)0.344a
Malignancy5 (20.8%)29 (19.0%)0.785a
Hepatic cirrhosis10 (41.7%)33 (21.6%)0.042a
Dialysis2 (8.3%)5 (3.3%)0.242a
Stent or vascular prosthesis1 (4.2%)14 (9.2%)0.697a
Artificial heart valve replacement3 (12.5%)9 (5.9%)0.211a
Osteoporosis or low density in CT (HU < 100)8/22 (36.4%)69/142 (48.6%)0.361a
Rheumatoid arthritis or increased rheumatic factors8/16 (50.0%)26/71 (36.6%)0.398a
Gout or increased uric acid6/13 (46.2%)36/74 (48.6%)1.000a
Chronic venous insufficiency0 (0.0%)5 (3.3%)1.000a
Peripheral artery disease3 (12.5%)7 (4.6%)0.138a
Atrial fibrillation7 (29.2%)35 (22.9%)0.606a
Disease-related complications
Disease-related mortality3/24 (12.5%)6/153 (3.9%)0.106a
Relapse rate5/12 (41.7%)21/104 (20.2%)0.137a
Sepsis20 (83.3%)67 (43.8%)<0.001a
Septic embolism elsewhere16/23 (69.6%)37/134 (27.6%)<0.001a
Meningism8/23 (34.8%)21/152 (13.8%)0.030 (1)
Success rate10 (41.7%)85 (55.6%)0.271a
Reoperation due surgical site infections4 (16.7%)22 (14.4%)0.759a
Reoperation due to empyema persistence or instability7 (29.2%)40 (26.1%)0.805a
Hospital stay43.5 [33.5–53.5] d31 [22–44] d0.003b
ICU stay2.5 [0–8] d1 [0–8] d0.614b
Modified Duke-Criteria
Definitive IE based on modified Duke-Criteria24 (100.0%)8 (5.2%)< 0.001a
Possible IE based on modified Duke-Criteria0 (0.0%)43 (28.1%)
Rejected IE based on modified Duke-Criteria0 (0.0%)102 (66.7%)

PSICIE vs. PSIWIE.

PSICIE, primary spinal infection concomitant infective endocarditis; PSIWIE, primary spinal infection without infective endocarditis; MSSA, methicillin-susceptible Staphylococcus aureus; CoNS, coagulase-negative Staphylococci; CT, computer tomography; EAT, empirical antibiotic therapy; TAT, targeted antibiotic therapy; CS, cervical spine; TS, thoracic spine; LS, lumbar spine; BMI, body mass index; HU, Hounsfield unit; ICU, intensive care unit; IE, infective endocarditis.

a

Fisher's exact test.

b

Mann–Whitney U test. Bold values are significant results (p < 0.05) as indicated in the methods.

Pathogens were detected more frequently via blood cultures in the PSICIE group (n = 23, 95.8%) than in the PSIWIE group (n = 88, 62.4%, p < 0.001). However, detection via intraoperative specimens (PSICIE: 18, 75% vs. PSIWIE: 119, 84.4%, p = 0.251) and via CT-guided biopsy of the psoas abscess (PSICIE: 6/8, 75.0% vs. PSIWIE: 29/51, 56.9%, p = 0.453) showed no difference between the two groups. PSICIE patients were treated more frequently with TAT strategy compared to PSIWIE patients (PSICIE: 16, 66.7% vs. PSIWIE: 45, 29.4%, p < 0.001), the opposite was observed for EAT strategy (PSICIE: 8, 33.3% vs. PSIWIE: 108, 70.6%, p < 0.001).

Polymicrobial infections, paravertebral psoas abscess, and CT-guided biopsy of paravertebral psoas abscess were equally distributed in both groups, however, PSICIE patients had more pleural abscesses than PSIWIE (PSICIE: 9, 37.5% vs. PSIWIE: 25, 16.3%, p = 0.024).The localization of infection in the spine, time to surgery, time to pathogen detection, the occurrence of incidental dural tears during surgery, the application of intraoperative antibiotic irrigation, the use of postoperative epidural suction-irrigation drainage, and the type of surgical procedure showed no significant difference between the two groups.

The PSICIE group had longer intravenous antibiotic duration (PSICIE: 6 [4–7] w vs. PSIWIE: 4 [2.5–6] w, p < 0.001) and longer total antibiotic duration (PSICIE: 11 [7.75–12] w vs. PSIWIE: 8 [6–12] w, p = 0.014). There was no between-group difference in the primary sources of infection (p = 0.231).

There was no significant difference in the distribution of primary sources of infection between the PSICIE and PSIWIE groups.

Hepatic cirrhosis was the only risk factor found more frequently in PSICIE patients than PSIWIE (PSICIE: 10, 41.7% vs. PSIWIE: 33, 21.6%, p = 0. 042), whereas the other risk factors such as immunosuppression, diabetes mellitus, obesity (BMI > 30 kg/m2), malignancy, dialysis, stent or vascular prosthesis, artificial heart valve replacement, osteoporosis, rheumatoid arthritis or elevated rheumatoid factors, gout or elevated uric acid, chronic venous insufficiency, peripheral arterial disease, and atrial fibrillation showed no difference between the groups.

Disease-related complications such as sepsis (PSICIE: 20, 83.3% vs. PSIWIE: 67, 43.8%, p < 0.001), septic embolism (PSICIE: 16/23 (69.6%) vs. PSIWIE: 37/134, 27. 6%, p < 0.001), and meningism (PSICIE: 8/23, 34.8% vs. PSIWIE: 21/152, 13.8%, p = 0.030) occurred more frequently in PSICIE patients than in PSIWIE patients. There was no difference between the two groups in disease-related mortality, relapse rate, success rate, reoperation due to surgical site infection, reoperation due to persistence of empyema or spinal instability.

PSICIE patients spent longer time in hospital (PSICIE: 43.5 [33.5–53.5] d vs. PSIWIE: 31 [22–44] d, p = 0.003), while ICU stay showed no significant difference between the two groups (PSICIE: 2.5 [0–8] d vs. PSIWIE: 1 [0–8] d, p = 0.614).

The modified Duke criteria showed a significant difference between the two groups as follows: definitive IE (PSICIE: 24, 100.0% vs. PSIWIE: 8, 5.2%), possible IE (PSICIE: 0, 0.0% vs. PSIWIE: 43, 28.1%), and rejected IE (0, 0.0% vs. PSIWIE: 102, 66.7%, p < 0.001).

3.3 Accuracy of modified duke-criteria in PSI patients

The modified Duke criteria have a sensitivity of 100% and a specificity of 66.7% for the diagnosis of IE in PSI patients.

3.3.1 Causative pathogens and type of infective endocarditis

3.3.1.1 Causative pathogens

MSSA was the most common causative pathogen in PSICIE patients (n = 13, 54.2%), followed by Staphylococcus epidermidis (n = 2, 8.3%), Streptococcus dysgalactiae (n = 2, 8.3%), S. pneumonia (n = 2, 8.3%), S. anginosus (n = 2, 8.3%), S. gallolyticus (n = 1, 4.2%), S. agalactiae (n = 1, 4.2%), and Aspergillus fumigatus (n = 1, 4.2%) (Figure 3).

Figure 3

3.3.1.2 Endocarditis type

The aortic valve IE was the most common type of IE in PSICIE patients (n = 12, 50%), followed by mitral valve IE (n = 5, 20.8%), tricuspid valve IE (n = 3, 12.5%), double valve IE (n = 2, 8.3%), and device-associated IE (n = 3, 12.5%) (Figure 4).

Figure 4

3.4 Multivariate regression analysis for the development of IE in PSI patients

Multivariate binary logistic regression analyses are summarized in (Table 3). Infection with Streptococcus spp. and Enterococcus spp. (p < 0.003; OR: 13.830; 95% CI: 2. 454–77.929), septic embolism (p < 0.005; OR: 4.387; 95% CI: 1.555–12.380), and hepatic cirrhosis (p < 0.011; OR: 4.383; 95% CI: 1.405–13.671) were identified as a significant independent risk factors for co-occurrence of IE and PSI in our cohort.

Table 3

VariablesMultivariate logistic regression
OR (95% CI)p-value
Age0.993 (0.932–1.058)0.822
Males2.321 (0.697–7.730)0.170
SD4.327 (0.505–37.074)0.181
CS0.857 (0.167–4.393)0.854
TS0.925 (0.072–11.962)0.983
LS1.926 (0.546–6.787)0.308
More than one part of the spine1.416 (0.360–5.560)0.618
Methicillin-sensitive Staphylococcus aureus3.703 (0.852–16.091)0.081
Streptococcus spp. and Enterococcus spp.13.830 (2.454–77.929)0.003
Paravertebral psoas abscess0.509 (0.121–2.143)0.357
Pleural abscess2.627 (0.850–8.120)0.093
Sepsis1.998 (0.432–9.239)0.375
Septic embolism4.387 (1.555–12.380)0.005
Meningism1.653 (0.416–6.570)0.475
Obesity (BMI > 30 kg/m2)1.121 (0.253–4.967)0.880
Immunosuppression1.499 (0.339–6.623)0.593
Diabetes mellitus1.307 (0.381–4.482)0.670
Malignancy0.469 (0.069–3.187)0.439
Hepatic cirrhosis4.383 (1.405–13.671)0.011
Dialysis0.339 (0.028–4.161)0.398
Stent or vascular prosthesis0.487 (0.46–5.180)0.551
Artificial heart valve replacement1.191 (0.136–10.406)0.874
Peripheral artery disease / chronic venous insufficiency3.238 (0.523–20.046)0.206
Atrial fibrillation0.497 (0.148–1.669)0.258

Multivariate analysis to identify independent risk factors for development of infective endocarditis.

SD, spondylodiscitis; CS, cervical spine; TS, thoracic spine; LS, lumbar spine; BMI, body mass index; OR, odds ratio; CI, confidence interval. Bold values are significant results (p < 0.05) as indicated in the methods.

Other factors such as age, gender, type of infection (SD, ISEE), localization at the spine, MSSA infection, paravertebral psoas abscess, pleural abscess, sepsis, meningism, obesity (BMI > 30 kg/m2), immunosuppression, diabetes mellitus, malignancy, dialysis, history of stent or vascular prosthesis, artificial heart valve replacement, peripheral artery disease or chronic venous insufficiency, and atrial fibrillation showed no significant difference in multivariate analysis.

4 Discussion

The main findings of this study were that hepatic cirrhosis, septic embolism, and infections with Streptococcus spp. and Enterococcus spp. were significant independent risk factors for the co-occurrence of IE and PSI. Furthermore, meningism, sepsis and pleural abscesses were found more frequently in PSICIE patients. IE occurred almost exclusively in SD, with MSSA being the most common pathogen and aortic valve IE being the most common type of IE in PSICIE subpopulation. All pathogens were GPB and could be detected via blood cultures up to 95.8%. The modified Duke criteria revealed a sensitivity of 100% and a specificity of 66.7% in the diagnosis of PSICIE patients.

The age and sex distribution, with a predominance of the male sex in both groups in our collective, was similar to that in previous studies (, ). Our study is, to the best of our knowledge, the first in which the two main representatives of PSI were assessed separately (SD and ISEE) with respect to IE. We were able to show that IE occurred almost exclusively in SD patients (95.8%).

Similar to the previous study, MSSA was the most common detected causative pathogen in both groups, while Streptococcus spp. and Enterococcus spp. were observed more frequently in the PSICIE group compared to the PSIWIE group (, ). In our study, the PSICIE group was found only in infections with GPB, as in a previous study (). The aortic valve (50.0%), followed by the mitral valve (20.0%), was the most frequently affected heart valve, as in the previous study ().

In our study, no pathogen could be detected in only 6.8% of PSI patients, which is substantially better than the existing literature because our collective underwent multiple blood culture tests, open surgery, and additionally CT-guided biopsy of the paravertebral psoas abscess in 53.6% (, ). Previous studies identified the pathogens by blood cultures, open surgery, or CT-guided biopsies. Sometimes a combination of two methods was used, but never all three simultaneously, which obviously improved the results.

We observed, as in Viezens et al. study, a significantly higher diagnostic sensitivity for blood cultures in the PSICIE group compared with the PSIWIE group (95.8% vs. 62.4%) (), which can probably be explained by the vegetation with consequent bacteremia; in contrast, there were no differences between the two groups for intraoperative sampling and CT-guided biopsy. The prompter detection of pathogens via blood cultures in the PSICIE group could perhaps explain why this group was managed more frequently with TAT.

Pleural abscesses were more common in the PSICIE group than in the PSIWIE group, which has not been previously studied in the literature. In contrast, the distribution of paravertebral psoas abscess was similar in both groups. The localization of PSI did not differ between the PSICIE and PSIWIE groups and is consistent with the results in the literature (, ).

The PSIECIE and PSIWIE groups were similarly surgically managed by either exclusive abscess evacuation or one- or two-stage surgery. The PSICIE patients spent more time in the hospital but not in the ICU, while the duration of intravenous antibiotic administration and the total duration of antibiotic administration were longer in the PSICIE group than in the PSIWIE group, similar to previous studies (, ).

We found more patients with hepatic cirrhosis in the PSICIE than in the PSIWIE group, and multivariate analysis showed that, in addition to septic embolism and pathogen type, hepatic cirrhosis influenced the co-occurrence of IE and PSI. This relevant information has not been reported or included in modified Duke criteria until now. Aagaard et al. observed an increased risk of death from hepatic cirrhosis in patients with spondylodiscitis in his study (). In nearly one-third of patients with cirrhosis, bacterial infection is present at hospital admission or develops during hospitalization (), and the mortality due to bacterial infection is four times higher in patients with cirrhosis than in patients without cirrhosis (33).

Sepsis, septic embolism, and meningism occurred more frequently in the PSICIE than in the PSIWIE group in our study, but only septic embolism was an independent factor for the development of IE, which was rightly included in the modified Duke criteria ().

To date, no multivariate analysis has been performed for the PSICIE subpopulation. Our multivariate analysis highlighted the importance of hepatic cirrhosis, septic embolism, and the presence of Streptococcus spp. and Enterococcus spp. in PSICIE patients.

Our study showed that the modified Duke criteria have high sensitivity and low specificity for PSICIE subpopulation, which has not been studied before and needs to be modified. Our data showed a significant difference between the PSICIE and PSIWIE group in terms of meningism, sepsis, septic embolism, hepatic cirrhosis, the presence of Streptococcus spp. and Enterococcus spp. and pleural abscess.

5 Limitations and strengths of this study

The monocentric, retrospective nature of our analysis, the long inclusion interval, and the limited number of the PSICIE group (24 patients) might reduce the external validity of our observations. Our study might also be affected by a possible selection bias, e.g., more severe cases due to transfers from surrounding hospitals and the high degree of specialization at our university center. However, our cohort analysis is based on a 20-year treatment period of SD and ISEE in a large university center for neurosurgery, suggesting a high internal validity of our study. Therefore, our observations may be useful to understand the clinical, microbiologic, and radiologic characteristics of the PSICIE subpopulation and the applicability of the modified Duke criteria in PSI patients.

6 Conclusions

In the understudied population of patients with PSI and concomitant IE, we identified distinct clinical, radiological, and microbiological phenotypes and we were able to confirm the diagnostic accuracy of the modified Duke criteria in these patients. The pathogen MSSA and the aortic valve as structural organ target seem to play an important role in the pathophysiology of PSICIE patients.

Moreover, we identified specific risk factors for co-occurrence of IE and PSI, including hepatic cirrhosis, septic embolism, and infections with Streptococcus spp. and Enterococcus spp. Pleural abscess, meningism, sepsis and hepatic cirrhosis might play an essential role in improving the modified Duke criteria in PSI patients and should be investigated in a prospective design.

Statements

Data availability statement

The original contributions presented in the study are included in the article Material, further inquiries can be directed to the corresponding author.

Ethics statement

The studies involving humans were approved by Ethics committee of the university hospital Dresden (Reference number BO-EK-17012022). The studies were conducted in accordance with the local legislation and institutional requirements. The ethics committee/institutional review board waived the requirement of written informed consent for participation from the participants or the participants’ legal guardians/next of kin because Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

Author contributions

MH: Conceptualization, Data curation, Investigation, Methodology, Project administration, Resources, Software, Validation, Visualization, Writing – original draft. TS: Writing – review & editing. IE: Writing – review & editing. AA: Writing – review & editing. PS: Writing – review & editing. MM: Writing – review & editing. DP: Writing – review & editing. GS: Writing – review & editing. TJ: Supervision, Writing – review & editing. IE: Writing – review & editing. AF: Supervision, Writing – review & editing.

Funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

Summary

Keywords

spondylodiscitis, vertebral osteomyelitis, isolated spinal epidural empyema, infective endocarditis, modified duke criteria

Citation

Hijazi MM, Siepmann T, El-Battrawy I, Aweimer A, Schröttner P, Mirus M, Podlesek D, Schackert G, Juratli TA, Eyüpoglu IY and Filis A (2024) The impact of concomitant infective endocarditis in patients with spondylodiscitis and isolated spinal epidural empyema and the diagnostic accuracy of the modified duke criteria. Front. Surg. 10:1333764. doi: 10.3389/fsurg.2023.1333764

Received

06 November 2023

Accepted

26 December 2023

Published

09 January 2024

Volume

10 - 2023

Edited by

Christoph Hohenberger, Universitätsklinikum Regensburg, Germany

Reviewed by

Basem Ishak, Heidelberg University, Germany

Jakob Rossmann, Paracelsus Medical Private University, Nuremberg, Germany

Updates

Copyright

*Correspondence: Mido Max Hijazi

Disclaimer

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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