doi: 10.2169/internalmedicine.5103-20
Intern Med 60: 1621-1625, 2021
http://internmed.jp
【 CASE REPORT 】
Spontaneous Pyogenic Spondylitis and Possible
Infective Endocarditis Caused by
Aggregatibacter actinomycetemcomitans
Naoko Yukihira 1, Hiroshi Hori 2, Takeshi Yamashita 2, Ai Kawamura 2,
Takahiko Fukuchi 2 and Hitoshi Sugawara 2
Abstract:
Aggregatibacter actinomycetemcomitans, an etiological agent associated with periodontitis, endocarditis,
and other infections, has rarely been implicated in spondylitis. A 70-year-old man with aortic valve replacement presented with a 4-month history of lower back pain and was diagnosed with spondylitis. Prolonged incubation of blood cultures and a biopsy yielded A. actinomycetemcomitans. Concurrent infective endocarditis
(IE) was probable considering the infectious organism and the patients’ prosthetic valve. The patient was
treated with ceftriaxone and recovered well. Pyogenic spondylitis with possible concurrent IE may be caused
by A. actinomycetemcomitans. Extended incubation and repeated cultures should be considered if Haemophilus spp., Aggregatibacter spp, Cardiobacterium spp, Eikenella spp, and Kingella spp. (HACEK) infection is
suspected.
Key words: Aggregatibacter actinomycetemcomitans, pyogenic spondylitis, infective endocarditis
(Intern Med 60: 1621-1625, 2021)
(DOI: 10.2169/internalmedicine.5103-20)
Introduction
Aggregatibacter actinomycetemcomitans belongs to the
HACEK (Haemophilus spp., Aggregatibacter spp, Cardiobacterium spp, Eikenella spp, and Kingella spp.) group of
bacteria, which are commensal microbiota that colonize the
oral-pharyngeal region in humans. The pathobiont A. actinomycetemcomitans has been implicated in periodontitis, endocarditis, and other infections (1); however, its association
with pyogenic spondylitis has rarely been reported.
We herein report a rare case in which A. actinomycetemcomitans infection developed concurrently with pyogenic
spondylitis and possible infective endocarditis (IE), as diagnosed by the modified Duke Criteria (2).
Case Report
A 70-year-old man with a history of aortic regurgitation
that had been treated with aortic valve replacement at 62
years old presented to the emergency department with lower
back pain. He had a four-month history of pain prior to
presentation. Previously, he had visited another hospital and
been treated with analgesics, which provided mild, shortterm symptomatic relief. In the absence of a specific diagnosis, the patient continued to experience pain in the proceeding months but was not marked by a fever, chills, or night
sweats. Three weeks before admission, he was brought to
our hospital by ambulance with recurring back pain, treated
with diclofenac, and discharged. However, the patient was
readmitted to our hospital as the chronic pain increased in
severity and he became unable to walk or stand.
Upon presentation, the patient was alert, and his vital
signs were as follows: temperature of 35.8℃, blood pressure
of 107/69 mmHg, regular heart rate of 70 beats/min, and
respiratory rate of 16 breaths/min. A physical examination
revealed anemic conjunctiva, periodontitis, mechanical valve
sounds, systolic murmur at apex, and L4-L5 tenderness. No
1
Department of Anesthesia, Tokyo Metropolitan Health and Hospital Corporation, Toshima Hospital, Japan and 2 Division of General Medicine,
Department of Comprehensive Medicine 1, Saitama Medical Center, Jichi Medical University, Japan
Received: April 16, 2020; Accepted: October 29, 2020; Advance Publication by J-STAGE: December 15, 2020
Correspondence to Dr. Hiroshi Hori, ubm5134@mbr.nifty.com
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Table 1.
DOI: 10.2169/internalmedicine.5103-20
Laboratory Data on Admission.
CBC
WBC
Neut
Lym
Mono
Eosi
Baso
RBC
Hb
Ht
MCV
MCH
PLT
11,190
84.0
9.0
6.0
0.0
1.0
270
8.0
24.2
89.6
29.6
43.1
Chemistry
/μL
%
%
%
%
%
*104/μL
g/dL
%
fL
pg
*104/μL
TP
Alb
AST
ALT
LDH
BUN
Cr
Na
K
Cl
CRP
ESR
7.7
2.8
15
16
192
27
1.05
136
4.6
106
12.3
134
g/dL
g/dL
IU/L
IU/L
IU/L
mg/dL
mg/dL
mEq/L
mEq/L
mEq/L
mg/dL
mm/h
Urinalysis
SG
pH
Prot
Glu
Uro
Bil
Ket
Bld
WBC
1.020
5.5
+/+/2+
-
Alb: albumin, ALT: alanine aminotransferase, AST: aspartate aminotransferase,
Baso: basophil, Bil: bilirubin, Bld: blood, BUN: blood urea nitrogen, CBC: complete blood count, Cl: chlorine, Cr: creatinine, CRP: C-reactive protein, Eosi: eosinophil, ESR: erythrocyte sedimentation rate, Glu: glucose, Hb: hemoglobin, Ht:
hematocrit, K: potassium, Ket: ketone, LDH: lactate dehydrogenase, Lym: lymphocyte, MCH: mean corpuscular hemoglobin, MCV: mean corpuscular volume,
Mono: monocyte, Na: sodium, Neut: neutrophil, PLT: platelet, Prot: protein,
RBC: red blood cell, SG: specific gravity, TP: total protein, Uro: urobilinogen,
WBC: white blood cell
Figure 1. A CT image of the lumbar spine shows an irregular
erosion of the superior end plate of the L5 vertebra (arrow)
and a possible fluid collection in the intervening L4/L5 disc
space. Abscess formation is not detected. CT: computed tomography
skin lesions or neurological symptoms were noted. Extensive periodontitis was confirmed by a dentist. Laboratory
tests showed a white blood cell (WBC) count of 11,190/μL
with 84% neutrophils, hemoglobin concentration of 8.0 g/
dL, C-reactive protein (CRP) of 12.3 mg/dL, and an erythrocyte sedimentation rate (ESR) of 134 mm/h. Other results
are shown in Table 1. His chest X-ray and electrocardiogram
findings were unremarkable.
Computed tomography (CT) of his lumbar spine showed
L5 end plate erosion (Fig. 1). No abscess formation was detected. Magnetic resonance imaging (MRI) revealed T1-
weighted low-intensity and T2-weighted high-intensity regions at the L4-L5 disc (Fig. 2A, B). This region showed a
high signal intensity on short tau inversion recovery (STIR)
imaging (Fig. 2C). The radiographic findings were suggestive of spondylitis of the L4-L5 spinal segment, and a CTguided needle biopsy was performed on hospital day 5. Empiric antibiotic therapy with ceftriaxone (2 g intravenously
daily) and vancomycin (target trough level of 15 to 20 μg/
mL) was administered after the biopsy.
The biopsy specimen subsequently yielded A. actinomycetemcomitans, which was also isolated from blood cultures
obtained on admission and hospital day 5 (Fig. 3). Blood
cultures required a prolonged incubation period of four days
to more than one week before growth was detected and several more days to identify the organism. The culture of the
biopsy specimen was positive on hospital day 13, and the
organism was identified on hospital day 15. Antibiotic
monotherapy was changed to ceftriaxone (2 g intravenously
daily) based on an antimicrobial susceptibility test (Table 2).
Since A. actinomycetemcomitans often causes endocarditis,
transesophageal echocardiography (TEE) was performed,
and neither vegetation nor destruction of valves were detected. Head MRI did not reveal findings suggestive of infectious lesions or a cerebral infarction. We also considered
positron emission tomography (PET)-CT for the prosthetic
valve endocarditis assessment but did not ultimately perform
it because it was not covered by insurance.
Antibiotic therapy was continued for eight weeks after a
negative blood culture was confirmed. This was in accordance with pyogenic spondylitis and IE treatment guidelines,
which recommend six to eight weeks of antibiotic therapy (3-7). The patient responded well to treatment, and his
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DOI: 10.2169/internalmedicine.5103-20
Figure 2. MRI of the lumbar spine. (A) T1-weighted image shows decreased signal intensity in the
L4 and L5 vertebral bodies (arrows) and loss of end plate definition (arrow head). (B) T2-weighted
image demonstrates increased signal in the L4/L5 interval disc space (arrow head). (C) Short tau inversion recovery image shows increased signal in the intervertebral disc space (arrow head) and adjacent L4 and L5 vertebral bodies (arrows). MRI: magnetic resonance imaging
Figure 3. Clinical course of the patient. Blood cultures were obtained on admission and hospital
day 5, both of which were positive, with the organism identified as A. actinomycetemcomitans after a
prolonged incubation period. A biopsy performed on hospital day 5 also yielded the same result. A
follow-up culture obtained on day 14 was confirmed negative, and antibiotic therapy was continued
for another eight weeks. The WBC, CRP, and ESR values showed marked declines after the antibiotic therapy was started. CRP: C-reactive protein, CTRX: ceftriaxone, ESR: erythrocyte sedimentation rate, VCM: vancomycin, WBC: white blood cell, wk: week
lower back pain was resolved. The CRP levels (0.09 mg/dL)
and ESR (40 mm/h) were markedly reduced after 5 weeks
of antibiotic therapy. The patient was transferred to another
hospital to continue antibiotic therapy and rehabilitation after 63 days of admission. There was no evidence of infection or pain recurrence in the 12-month follow-up period.
Discussion
This report indicated that a patient with the insidious onset of back pain and a history of heart valve replacement
and extensive dental disease concurrently developed pyo-
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genic spondylitis and possible IE caused by A. actinomycetemcomitans. Extended incubation and repeated blood cultures led to the detection and identification of the pathogenic
organism.
Three important clinical issues were noted from the clinical course of this patient: 1) A. actinomycetemcomitans may
cause pyogenic spondylitis, 2) Concurrent IE may have been
present in this A. actinomycetemcomitans-mediated spondylitis case, and 3) Infection was caused by A. actinomycetemcomitans.
First, to our knowledge, only five cases of pyogenic spondylitis caused by A. actinomycetemcomitans have been reported (8-12) (Table 3). This limited number of reports may
suggest a low frequency of infections. However, there may
be some unrecognized A. actinomycetemcomitans spondylitis
cases. A systematic review of 14 studies including 1,008 patients with pyogenic spondylitis reported that the yield of
blood culture was 30-78%, while a CT-guided needle biopsy
or open biopsy provided a yield of 47-100%, and overall,
the causative organism of pyogenic spondylitis was unknown in up to 33% of cases (13). Slow growth of A. actinomycetemcomitans is observed in standard culture media,
and isolation requires prolonged incubation (8, 9, 11). Typically, only a small fraction of blood culture bottles in patients with HACEK-linked IE demonstrate growth, and the
Table 2. Susceptibility Test Results.
Antimicrobial agents
MIC (μg/mL)
Susceptibility
Ampicillin
Sulbactam/ampicillin
Cefotaxime
Ceftriaxone
Meropenem
Clarithromycin
Levofloxacin
Sulfamethoxazole/trimethoprim
1
1
<0.25
<0.25
<0.125
8
<0.5
<10
S
S
S
S
S
S
S
S
The identified organism was susceptible to all of the above listed antimicrobial agents. An “ID test HN20 rapid” panel and mass spectrometry were used
to identify the bacterial species. In addition, the MIC obtained by the broth
microdilution method and the CLSI (The Clinical & Laboratory Standards
Institute) M45 breakpoints were referred to in determining the susceptibility.
S: susceptible, MIC: minimum inhibitory concentration
HACEK group is often associated with culture-negative IE
cases (5). Furthermore, capsular material from this organism
has been thought to be a potent mediator of bone resorption (14). This implies that A. actinomycetemcomitans can
cause bone infection in the setting of bacteremia. Thus,
there may be latent A. actinomycetemcomitans spondylitis
cases considering the fastidious character and virulence of
the pathogen.
Second, concurrent IE may be present in patients with
pyogenic spondylitis caused by A. actinomycetemcomitans.
In general, vertebral spondylitis is a complication of bacteremia, and associated endocarditis is seen in some patients. A
retrospective review including 91 cases of vertebral spondylitis identified 28 patients (31%) with IE (15). Although
none of the five previously described cases of pyogenic
spondylitis due to A. actinomycetemcomitans had an IE
complication (8-12), bacteremia caused by a HACEK organism is highly suggestive of IE. In addition, A. actinomycetemcomitans is most commonly involved in IE compared
to the rest of the HACEK group (16, 17). Although TEE detected no apparent vegetation, IE was “possible” in this patient because the blood culture yielded A. actinomycetemcomitans, and the patient had a prosthetic valve, which satisfies one major (blood cultures) and one minor (predisposing
heart condition) modified Duke criterion (2). Furthermore,
the patient had two of the risk factors for A. actinomycetemcomitans endocarditis: a history of valve damage or valve
replacement surgery and dental disease (17). An evaluation
for concurrent IE is warranted even though the duration of
therapy for pyogenic spondylitis is adequate for the treatment of IE in most cases (3-7). Patients with IE require additional follow-up evaluations for valvular disease as well as
prophylactic antibiotics for the prevention of subsequent IE.
Finally, the present patient’s clinical course suggested that
an extended incubation period and repeated sampling for
cultures would be required for the detection and identification of A. actinomycetemcomitans. In this patient, blood culture from the outpatient clinic was negative after seven days
of incubation. The second and third blood cultures were obtained on admission and hospital day 5, respectively. The
third culture was positive for Gram-negative rods (GNRs)
after four-day incubation, while the second culture remained
negative at that point. We requested two-week incubation of
Table 3. Previously Reported Pyogenic A. actinomycetemcomitans Spondylitis Cases.
Case
Age/Sex
Endocarditis
Complicaton
Treatment
Reference
1
45/M
8
66/M
65/M
72/M
cefotaxime 2 weeks → amoxycillin 4 weeks
antibiotic (detail unknown) 6 weeks
debridement + ceftriaxone 6 weeks
9
10
11
5
52/F
axillary
abscess
nil
nil
epidural
abscess
nil
ampicillin 6 weeks
2
3
4
Evaluated but no
evidence of IE
Not mentioned
Not mentioned
Evaluated but no
evidence of IE
Evaluated but no
evidence of IE
ceftriaxone 4 weeks → levofloxacin 6 weeks
12
F: female, M: male, IE: infective endocarditis
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DOI: 10.2169/internalmedicine.5103-20
the second culture because the patient had a prosthetic heart
valve and HACEK infection was possible. Later, the second
culture proved positive for GNRs as well, requiring over a
week of incubation time. The GNRs were subsequently
identified as A. actinomycetemcomitans. Recent studies have
shown that HACEK bacteria can be isolated using standard
culture methods and media within a standard five-day incubation period (18, 19). However, our case required a longer
incubation period and repeated cultures before growth was
detected. A review of 102 IE cases also found that the mean
duration to obtain a positive blood culture was 7.1 days,
with a range of 1-15 days. Therefore, extended incubation
and repeated blood cultures should be considered if a
HACEK infection is suspected.
In conclusion, although the frequency is low, A. actinomycetemcomitans can cause pyogenic spondylitis and concurrent IE.
There
may
therefore
be
latent
A.
actinomycetemcomitans-mediated spondylitis cases. Patients
with spondylitis, a history of heart valve disease and extensive dental disease, and for whom blood cultures remain
negative might have infection caused by A. actinomycetemcomitans. Upon presentation of these signs, extended incubation and repeated blood cultures must be employed to detect and identify the pathogenic organism. Further research
is needed to obtain a reliable estimate of the frequency of A.
actinomycetemcomitans spondylitis and the coexistence of
IE.
The authors state that they have no Conflict of Interest (COI).
Acknowledgement
This case was presented at the 31st International Congress of
Antimicrobial Chemotherapy and 4th Gulf Congress of Clinical
Microbiology and Infectious Diseases (31st ICC - 4th GCCMID
2019).
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