Spondylodiscitis - Related Endocarditis
Abstract
Keywords: Spondylodiscitis; Endocarditis; Hematogenous spread; Antibiotics; Pathogenic microorganisms
Abbreviations:
IE: infective endocarditis; SD: spondylodiscitis; CBC: Complete
Blood Count; CRP: C-
reactive protein; DVT: deep vein thrombosis; CT: computed tomography; TTE: transthoracic
echocardiogram; MRI: magnetic resonance imaging; TΟE:
transoesophageal echocardiogram; HIV: human immunodeficiency virus; ESR:
erythrocyte sedimentation rate; WBC: white blood count; CVC: central venous
catheter; PICC line: peripherally inserted central catheter; 18F-FDG-PET/CT: Positron
emission tomography (PET) with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG)
1. Introduction
The correlation between IE and SD was first
established in 1965. Both of these infections are quite challenging to
diagnose, and therefore, individuals who are predisposed, and report symptoms
as described below, need to be thoroughly examined. Infection arises due to
bacteremia, as a result of various causes. To diagnose both conditions, a
protocol needs to be followed, including a series of examinations that can
reveal an active infection, such as hematologic tests [erythrocyte
sedimentation rate (ESR), Complete Blood Count (CBC) and C- reactive protein (CRP)], blood cultures
to identify the pathogenic agent, and imaging studies that may reveal
abnormalities. It is critical to identify the etiological factor, for the
therapeutic plan to be targeted and customized for the specific pathogen. With
the use of appropriate antibiotics, mortality has significantly decreased,
while surgical intervention takes place in cases where it is deemed necessary.
In this article, we present the case of a 35-year-old man who was admitted to
our hospital with findings of spondylodiscitis, and during his hospitalization,
concomitant endocarditis was identified.
2. Case report
A 35-year-old male patient was admitted to the
Emergency Room of AHEPA Hospital with progressively worsening lumbar pain that
initially developed four months ago. The patient’s medical history included
deep vein thrombosis (DVT) of the right lower limb, post-COVID syndrome,
hepatitis C, thrombosis of the left femoral artery, and intravenous drug use
(IVDU).
The patient was admitted to the Internal
Medicine Department. The physical examination showed lumbar pain, with motor
difficulty that was attributed to the pain, without any neurological deficit.
The laboratory results showed increased CRP levels at 10.21 mg/dl, and anemia
(hemoglobin: 10.6 g/dl).
Blood cultures and complete serological tests were
performed. A computed tomography (CT) scan with a contrast agent showed
significant vertebral endplate lesions in the L3-L4 disc space, architectural
changes, subchondral damage, endplate sclerosis, anterior syndesmophyte, and
intervertebral disc space narrowing
Figure 1. CT of the spine showing endplate sclerosis and
irregularity (A). Mildly enhanced soft tissue between the spine and abdominal
aorta (B)
Ceftriaxone, vancomycin, and gentamycin were
initiated. Following the neurosurgical assessment, a three-point thoracolumbar
brace was applied.
Transthoracic echocardiography (TEE) showed
agile mitral valve formation. A transesophageal echocardiogram (TOE) was
scheduled to further assess whether it was a vegetation or an artifact, which
was not completed; however, due to lack of cooperation. Magnetic resonance
imaging (MRI) confirmed spondylodiscitis in the L3-L4 disc space (Figure 2).
On the tenth day of hospitalization, the patient
developed a high body temperature (37.5oC). The central venous line
was replaced, a new set of blood and urine cultures were taken, and chest
radiography was performed. The treatment was changed to piperacillin-tazobactam
and daptomycin.
During the administration of
piperacillin-tazobactam, the patient developed a maculopapular rash throughout
his body and was treated with systemic administration of antihistamines
(levocetirizine). A new MRI scan showed bone marrow edema and contrast
enhancement of the L3 and L4 vertebral bodies, pedicles, pars interarticular,
facet joints, and intervertebral discs (Figure 3).
Figure 3. Spine MRI revealed bone marrow edema (A) and contrast enhancement of the L3 and L4 vertebral bodies, pedicles, pars interarticular, facet joints, and intervertebral disc (C, G). Inflammatory changes and enhancement of the adjacent psoas (D) with small intramuscular abscesses (E).
Concomitant
leptomeningeal enhancement (H). The second bone marrow lesion in the L5 body
(C).
On the 20th day of hospitalisation, the
patient again developed high body temperature (39 oC) and complained
of chest pain. He also reported numbness in the right upper limb and right
lower limb combined with spontaneous and involuntary movements of the right
upper limb that lasted approximately 5 min. We suspected endocarditis as the
initial diagnosis. A new set of blood cultures were obtained. A
transoesophageal echocardiogram (TΟE) followed, which revealed vegetation on
both the tricuspid valve and the tip of the central venous catheter (CVC), thus
confirming the diagnosis of endocarditis. In such a case, we are dealing with
right heart involvement; the patient has some artificial material on the right
side of the heart (vascular port, as in this case). The CVC was immediately removed. A PICC line
(peripherally inserted central catheter) was placed through the basilic vein of the arm. The
antibiotic treatment was changed to meropenem, vancomycin, gentamicin, and micafungin.
Neurological assessment and brain CT showed no significant findings. In the
lungs, endocarditis on the right-side cause’s lung abscesses. Interestingly,
lung computed tomography (CT) screening results revealed no abnormalities or
indications of disease. Brain magnetic resonance imaging (MRI) revealed
findings indicating possible septic emboli (Figure 4).
Figure 4. Spine MRI on 21st day depicted a further
significant reduction in paravertebral inflammation (F) and dural enhancement
(G). Bone marrow edema is also slightly reduced (A, B).
A new spinal MRI on the 30th day of hospitalisation showed significant improvement (Figure 5). A significant observation in this case was the absence of pathogenic organisms. Moreover, the patient recovered fully without any complications, which contradicts
Figure
5. Spinal MRI on the 30th day showed a further
reduction in bone marrow oedema (B). Adjacent psoas inflammatory changes are
significantly reduced (F).
1.
Discussion
Spondylodiscitis is an infection involving the
intervertebral disc and adjacent vertebral bodies, resulting from pathogenic
microorganisms that migrate through the bloodstream, either venous or arterial,
with the latter being more common1.
Additionally, it can be attributed to infections from a distant site
(endocarditis, abscess, urinary tract infection, pneumonia, or pelvic
infection), and it can develop postoperatively, following surgery at a distant
site (pelvic, urological, vascular, cardiac, or internal organ surgery), with a
local infection becoming systemic or arising from intravenous use of illicit
drugs2. The most affected age groups
are individuals under 20 years old, especially those infected with the human
immunodeficiency virus (HIV), and adults aged 50-70 years1.
When an intervertebral disc is infected, the
condition is referred to as discitis, and when the infection involves the
endplate, it is referred to as osteomyelitis or spondylitis. Typically, at the
time of diagnosis, both anatomical regions are affected; hence, the term
spondylodiscitis is used in most cases (95%), which affects the vertebral body
more than the posterior elements (5%)2.
Infections of the spinal column are usually
classified according to the causative microorganism, such as pyogenic,
parasitic, fungal, or tuberculous. Tuberculosis has historically been the
primary cause of spinal infections; however, due to the successful diagnosis
and treatment of pulmonary tuberculosis, its incidence has decreased over the
last 50 years3. According to an
analysis by Grammatico L, et al., Staphylococcus
spp. are the main infectious agents that cause spondylodiscitis (38%);
gram-negative bacilli, including enterobacteria (20-30%); and streptococci,
with Mycobacterium tuberculosis and Brucella spp. being less prevalent4.
However, as observed in this case, as many as
one-third of the infectious agents may remain unidentified3. Additionally, pyogenic spondylodiscitis
predominantly affects the lumbar region of the spinal column (58%), followed by
the thoracic (30%) and cervical (11%) regions4.
The adult intervertebral disc, being avascular,
undergoes involution of intraosseous anastomosis around the third decade of
life. With aging, this leads to the release of septic emboli, causing extensive
vascular bone infarcts and spreading of infection to adjacent structures,
resulting in characteristic imaging findings of spondylodiscitis, including
erosion4.
Patients suffering from spondylodiscitis develop
local pain, accompanied by muscular spasms that are attributable to
inflammation, fever, and neurological deficits. The clinical picture is
nonspecific, with low-specificity indicators and symptoms, leading to delayed
diagnosis, particularly in the tuberculous form, as well as delayed treatment1. Literature data report a delay of 2-6 months
between the onset of initial symptoms and diagnosis5,6. Diagnosis is challenging, and clinical, laboratory, and
imaging findings1.
In clinical practice, the laboratory parameters
that specialist medical practitioners focus on mostly refer to elevated levels
of inflammatory markers, such as erythrocyte sedimentation rate (ESR) and
C-reactive protein (CRP), where, similar to the case under study, values exceed
the normal limits5. ESR is a
sensitive indicator of infection, and it is high in the majority of patients
(90%). However, it is a nonspecific marker of infection. CRP is an acute-phase
protein with greater specificity than ESR and is also observed at increased
levels in 90% of patients with spondylodiscitis1.
The white blood cell count (WBC) may be elevated
or within the normal range in patients with spinal column infection. However,
although it is not a specific infection marker for patients with
spondylodiscitis, it should be included in the diagnosis and treatment process,
especially in cases accompanied by fever, thus providing general information
about the patient's course of treatment7.
The imaging examinations that are conducted in
each case are crucial in disease diagnosis. Although it has low specificity
(57%), a radiographic examination should be performed to all patients with
suspected spondylodiscitis. In advanced cases, it may reveal abnormalities in
the end-plates of the vertebrae, with eventual fragmentation, and reduced
height of the intervertebral disc5.
Axial tomography (CT) remains the preferred
examination for evaluating bone changes, including the identification of early
alterations in vertebral end-plates, the presence of bone necrosis, and
pathological calcifications that indicate tuberculosis5.
The only imaging method that combines high
sensitivity (97%) with satisfactory specificity (94%) is gadolinium-enhanced
magnetic resonance imaging (MRI), which provides detailed anatomical
information about the surrounding soft tissues, i.e., highlighting bone
abnormalities, and detecting paraspinal or epidural abscesses9. It is highly useful in the early stages of
infection when other imaging methods remain inconclusive (e.g. radiography)5.
In cases of negative blood cultures, a
recommended patient management algorithm involves withholding antibiotics until
a CT-guided biopsy/aspiration is performed. Biopsy samples should be sent for
polymerase chain reaction (PCR) testing, and checked for Gram stain, aerobic,
and anaerobic cultures, tuberculosis, and fungi. The accuracy of CT-guided
spinal biopsy is approximately 70%, with false negatives being possible, in
cases of insufficient tissue sampling or antibiotic administration. Repeat
biopsy may be considered, if antibiotic cessation is deemed safe and initial
biopsy results are negative7.
The most common comorbidities were sepsis (27%),
and endocarditis (9%)4. On the other
hand, infectious endocarditis is a rare, but highly morbid, and fatal,
condition (30%)9. It is characterized
by infection of a native or prosthetic cardiac valve, endocardial surface, or
permanent cardiac device, causing inflammation in the heart's endothelium10.
The infection is associated with healthcare
interventions, resulting from the use of intravascular catheters, and
intracardiac devices. The most common cause of the disease is the following
pathogenic microorganisms, collectively accounting for 90% of endocarditis
cases. Specifically, Staphylococcus aureus constitutes 26.6% of cases, followed
by viridans group streptococci, at 18.7%, other streptococci, at 17.5%, and
enterococci, at 10.5%9.
The clinical picture varies, and clinicians
should be alert to symptoms for prompt diagnosis. It may manifest as an acute
and rapidly progressing infection, or as a subacute or chronic disease, with
low-grade fever, and nonspecific symptoms that can be misleading. Fever, night
sweats, fatigue, weight loss, and anorexia are common, with up to 85% of
patients having cardiac murmurs. Notably, embolisation of the brain, lungs, and
spleen occurred in 30% of the patients. Special attention should be paid to patients
with predisposing risk factors (protrusion of the mitral valve, congenital
heart disease, previous endocarditis, patients with implanted cardiac devices,
etc.). Some of the comorbidities of infectious endocarditis include intravenous
drug use, chronic kidney disease (especially in patients undergoing
hemodialysis), chronic liver disease, advanced age, corticosteroid use,
uncontrolled diabetes, central venous catheter, and immunocompromised status
(including HIV infection)9.
Diagnosis of infectious endocarditis relies on
modified Duke Criteria (Table 1), with imaging studies, such as CT, MRI,
and 18F-FDG PET/CT, playing a crucial role11.
Transesophageal echocardiography (TOE) is performed to confirm diagnosis, in
cases of no diagnostic transthoracic echocardiography (TTE) with a high
clinical suspicion, especially in cases involving prosthetic devices, and
Staphylococcus aureus bacteremia. Imaging repetition is generally unnecessary
during treatment unless clinical deterioration or complications occur9.
Table 1. Major and Minor Criteria for the diagnosis of
infective endocarditis, and its complications.
|
Major Criteria |
|
|
|
Microbiological Criteria |
|
|
|
Isolation of typical microorganisms responsible for infective
endocarditis (IE), from two different blood cultures. The microorganisms include Streptococcus bovis, the HACEK group,
Staphylococcus aureus, and Enterococcus. |
Persistent positive blood cultures, indicating the presence of
microorganisms that are compatible with the diagnosis of IE. The criteria
include 2 blood cultures taken with a minimum 12-hour interval in-between, or
3 positive blood cultures taken at different times. Additionally, isolation
of microorganisms from most blood cultures, when four or more are taken, with
the first and last cultures separated by at least one hour |
Detection of Coxiella burnetii in a single positive blood culture,
positive PCR, or serological evidence of Q fever. |
|
Evidence of Myocardial
Involvement |
|
|
|
Development of valve insufficiency not previously present.
Exacerbation or alteration in pre-existing murmurs is insufficient. |
Positive echocardiogram for microbial endocarditis, involving the
visualization of intracardiac masses that are consistent with vegetation,
without alternative anatomical explanations, or the presence of abscess. |
New valvular regurgitation in prosthetic valves. |
|
Minor Criteria |
|
|
|
Pre-existing cardiac damage or use of intravenous toxic substances. |
|
|
|
Fever ≥38.0°C |
|
|
|
Vascular phenomena |
Arterial emboli, septic pulmonary infarcts, mycotic aneurysm,
intracranial hemorrhage, Janeway lesions |
|
|
Microbiological evidence |
Positive blood cultures
(different from those outlined in major criteria) or serological evidence of
an ongoing infection with microorganisms compatible with the diagnosis of
microbial endocarditis. |
|
|
Immunological phenomena |
Glomerulonephritis, Osler's nodes, Roth spots, rheumatoid factor. |
|
Collaboration between various medical specialties, including cardiologists, internists, infectious disease specialists, neurosurgeons, neurologists, and cardiothoracic surgeons, is essential, for both the diagnosis and management of infectious endocarditis. Coordination among these specialists leads to prompt referral with appropriate therapeutic (conservative or surgical) protocols and close patient monitoring to reduce mortality (Table 1)9.
Spondylodiscitis (SD) is a recognized
complication of IE, possibly stemming from the hematogenous spread of
infectious agents12.
According to studies by Del Pace S. et al. and Carbone A. et al. a significant percentage of IE patients experience SD (8-30%). The correlation between these conditions is common, with specific
microorganisms involved. In particular, Streptococcus Viridans and Enterococcus
are prevalent in IE and SD cases. Neurological symptoms and embolic phenomena
are observed in both conditions.
The majority of cases of endocarditis reported
involvement of the aortic valve at a rate of (53%), with mitral (40%) and
tricuspid (7%) valve involvement being less prevalent. In cases of
spondylodiscitis, intense lumbalgia (low back pain) (26.90%) was noted13. Timely diagnosis is crucial and relies on
advanced imaging techniques such as magnetic resonance imaging (MRI) and PET/CT14.
Additional studies by Viezens L. et al.
emphasize the value of echocardiography and TOE to the diagnostic process,
demonstrating a tenfold increase in diagnosed IE, after applying
transesophageal echocardiography (TOE) to patients with known spondylodiscitis12.
Therapy is based on combined antimicrobial
treatment, according to the sensitivities of the isolated pathogen cultured
from material obtained through paracentesis and/or blood cultures. Antibiotics,
including penicillin and first-generation cephalosporins, are used to treat
common infectious organisms such as Staphylococcus and Streptococcus. For
immunocompromised patients and intravenous drug users, broad-spectrum
antibiotics are added, such as third-generation cephalosporins with better
coverage against Gram-negative bacteria3.
Clindamycin, vancomycin, quinolones,
tetracycline, and cotrimoxazole also exhibit good bone-penetrating properties
and should be considered in the treatment of spinal infections, especially in
patients sensitive to beta-lactam antibiotics. Antibiotic treatment for less
than four weeks may result in high recurrence rates. Empirical antibiotic
therapy is recommended in the absence of pathogen detection, and the antibiotic
spectrum should cover S. aureus and E. coli, which are the most common
pathogens for pyogenic spondylodiscitis, taking into account local epidemiology
and the possibility of colonization by resistant organisms2,3.
The discontinuation criteria for treatment
include the restoration of clinical and inflammatory markers, such as
erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). CRP is
considered a better indicator of treatment response, and its reduction is
faster than that of ESR15.
Hsiu-Yin Chiang et al. suggest that the initial
ESR value and its variability in the first 4 weeks are useful indicators for
predicting the duration of treatment and recurrence of spondylodiscitis.
However, ESR levels normalize slowly and irregularly, even after successful
infection treatment15.
Surgical intervention was performed according to
specific indications such as the presence of neurological deficits and
deformity. Absolute surgical indications include spinal instability due to
extensive bone destruction, severe kyphosis, and failure of conservative
treatment. However, specific criteria, such as age and the general condition of
the patient, should be considered5.
According to Yoshimoto et al., in a study of 45
patients aged 65 years and older with pyogenic spondylodiscitis, some of whom
presented with paralysis but were not operated on because of poor general
health conditions and relevant problems, paralysis improved with conservative
treatment in a significant percentage of the patients16.
The use of antibiotics significantly reduced IE
mortality of infective endocarditis. However, their use requires good renal
function, which should be adjusted accordingly. The guidelines for empirical
therapeutic regimens mention amoxicillin intravenous in stable
patients, because it has better activity against enterococci and many HACEK
microorganisms than benzylpenicillin. The role of gentamicin (IV) remains
controversial until positive blood cultures are obtained, and should be used
with caution in cases of nephrotoxicity or renal impairment. In severe sepsis
without concerns for enterobacteria and Pseudomonas, vancomycin is preferred,
and daptomycin is administered in allergic patients. In severe sepsis and risk
factors for multidrug-resistant enterobacteria and Pseudomonas, vancomycin (IV)
and meropenem are administered17.
In several cases, we are dealing
with right heart involvement, either with a fistula (emptied abscess) from the
left heart or with a drug addict, or the patient has some artificial material
on the right side of the heart (pacemaker leads, ICD, vascular port, as in this
case). Vegetation on the right side can be removed endovascularly and is both
curative and diagnostic (this can be seeded if vein cultures are still
negative).
Regarding spondylodiscitis, patients who do not
improve with conservative treatment and experience recurrence should undergo
prompt surgery18.
2.
Conclusion
Although the association of infective endocarditis
with spondylodiscitis is not rare, short-term mortality in infective
endocarditis still exceeds 15%. Diagnosis is challenging, and clinical,
laboratory, and imaging findings should be considered. The main targets of
treatment are the isolation and identification of microorganisms, prevention of
bacteremia and sepsis, elimination of infection, long-term pain relief,
reversal of neurological deficits, restoration of spinal stability, and
prevention of relapse. Rapid diagnosis and conservative or surgical treatment
are key prerequisites for positive outcomes.
Conflict of interest: None declared.
Funding: None
declared.
Patient consent: The patient has given written consent to the inclusion
of material pertaining to himself; he acknowledged that he cannot be identified
via the paper, and we have fully anonymized the case report.
Ethical approval: Not applicable
Authors’ contributions
AM: primary case-management, literature review and
manuscript preparation.
EP, CK, VK: literature review
All authors read and approved the final manuscript.
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Sánchez PM. Spondylodiscitis. Radiologia
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Rajani R, Klein JL. Infective endocarditis: A
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