PRACTICE | WHAT IS YOUR CALL?

SEPSIS

A 59-year-old man with persistent fever,
aphasia and leg pain
Benoît M.-Labbé MD MSc, Pierre-Luc Harvey-Michaud MD, Alexandre Lafleur MD MSc
n Cite as: CMAJ 2021 April 12;193:E517-20. doi: 10.1503/cmaj.201491

A

59-year-old man presented to the emergency department with fever and chills that began 6 weeks earlier,
when a symptomatic deep vein thrombosis (DVT) of
the right posterior tibial vein had been diagnosed. The patient
had also noticed word-finding difficulties and mild headache
for the week before the current presentation. He did not have
any chest pain, nausea or loss of consciousness. The patient
was receiving anticoagulation treatment for his distal DVT
with rivaroxaban (20 mg daily) because of his history of a
squamous cell carcinoma of the tongue, which had been
treated 2 years earlier.
On physical examination, the patient’s body temperature was
38.1°C, with otherwise normal vital signs. Cardiac auscultation
found a 3/6 holosystolic murmur heard best over the apex.
Neuro­logic examination was normal except for a subtle expressive aphasia. Vascular examination of the extremities was normal. Initial laboratory tests reported a leukocyte count of
4.4 (normal 4.8–10.8) × 109/L, a hemoglobin level of 131 (normal
140–175) g/L, an erythrocyte sedimentation rate of 17
(normal < 10) mm/h and a creatinine level of 92 (normal
49–93) μmol/L. The patient’s liver enzyme and electrolyte levels
were normal. Two blood culture sets were drawn.

Which neurologic diagnosis needs to be ruled
out in this patient?
a. Hemorrhagic stroke
b. Cardiogenic or paradoxical embolic stroke
c. Infection of the central nervous system
d. Cerebral metastasis
e. All of the above
The answer is (e). Our patient’s history of cancer and recent
DVT raised concerns about cerebral metastasis and paradox­
ical embolic stroke. In addition, we were concerned about
infective endocarditis, given the combination of fever, a new
heart murmur and aphasia. Septic emboli can lead to ischemic
or hemorrhagic strokes, meningitis or cerebral abscesses, and
would not be prevented by the anticoagulation treatment
for DVT.

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What additional investigations should be
ordered urgently?
a. Lumbar puncture
b. Computed tomography (CT) of the head, with and without
contrast
c. Two additional blood cultures drawn at least an hour later
d. Transthoracic echocardiography
e. Transesophageal echocardiography
The answer is (b). Although (c), (d) and (e) were all indicated investigations, a CT of the head was most urgent because our patient
had acute neurologic signs while taking anticoagulants. Computed
tomography angiography (CTA) can identify a proximal arterial
occlusion or an intracranial mycotic aneurysm.1,2 The American
Heart Association (AHA) 2015 guideline recommends cerebrovascular imaging in all patients with a suspected diagnosis of infective
endocarditis presenting with neurologic symptoms.1 Computed
tomography angiography, magnetic resonance angiography or
digital subtraction angiography may be used when intracranial
aneurysms are suspected and should also be considered with leftsided infective endocarditis for early detection of mycotic aneur­
ysms, even in the absence of neurologic signs.1
When infective endocarditis is suspected, the AHA guideline
recommends at least 3 sets of blood cultures, obtained from different venipuncture sites, with first and last samples drawn at
least 1 hour apart.1 Additional blood cultures should therefore be
obtained without delay because the possibility of sepsis warrants prompt initiation of antibiotic treatment. We began empir­
ical therapy with intravenous ceftriaxone (2 g every 12 h) and
vancomycin (1 g every 8 h) to cover the most common pathogens
associated with subacute community-acquired native valve
endocarditis (i.e., staphylococci, streptococci and enterococci).1,2
Because we suspected cerebral septic emboli, meningeal doses
were given.
Transthoracic echocardiography should also be performed as
soon as endocarditis is suspected. Transesophageal echocardi­
ography is more sensitive and is indicated in patients with a
­negative or nondiagnostic transthoracic echocardiograph and a
high index of suspicion for endocarditis. Transesophageal

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Figure 1: Axial views of (A) computed tomography and (B) fluid-attenuated inversion recovery magnetic resonance imaging of the head showing left
parietal–temporal acute ischemic stroke (oval) with signs of localized adjacent convexal subarachnoid hemorrhage (black and white arrows).

e­ chocardiography is also mandatory when clinicians suspect
intracardiac complications, such as a paravalvular abscess, a
pseudoaneurysm or a fistula, and may be considered in all
patients after a positive result on transthoracic echocardiog­
raphy.1,2 Lumbar puncture was contraindicated in our patient
because of oral anticoagulation treatment.
Computed tomography and magnetic resonance imaging of
our patient’s head showed a left parietal–temporal subacute
ischemic stroke with signs of localized adjacent nontraumatic
convexal subarachnoid hemorrhage, without arterial abnormal­
ities (Figure 1). Rivaroxaban was immediately suspended. Both
types of echocardiography confirmed a new-onset severe mitral
valve regurgitation and multiple vegetations (≤ 5 mm) on its
anterior leaflet. No patent foramen ovale was identified by bubble studies using agitated saline.
Four blood cultures identified the presence of Enterococcus
faecalis susceptible to penicillin, ampicillin, vancomycin and
gentamicin (our interpretation was based on the Clinical and
Laboratory Standards Institute guideline [https://clsi.org/] and
reported as categorical results). Our patient’s echocardiographic and cerebral imaging findings met the Duke diagnostic
criteria for infective endocarditis with probable cerebral
emboli.1 We adjusted our patient’s treatment with antibiotics to
intravenous penicillin G (4 million units every 4 h), and we added
gentamicin (3 mg/kg divided in 2 doses) for its synergistic effect.
Ceftriaxone plus ampicillin would have been an appropriate
alternative regimen, especially in the presence of chronic kidney
disease or frailty, where the risk of aminoglycoside toxicity is
especially high.1

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Endocarditis related to E. faecalis is usually associated with
genitourinary procedures or bacteriuria, neither of which
applied to our patient.3 Other potential sources include colorectal neoplasms, and inflammatory lesions of the gut and biliary
tree. For this reason, we arranged for CT of the abdomen and
pelvis, and a colonoscopy, all of which were normal.3,4 These
investigations, combined with a thorough history and physical
examination, completed our patient’s age-appropriate cancer
screening, which is indicated in the context of idiopathic DVT.5
Because of our patient’s history of tongue carcinoma, we also
investigated cancer recurrence with nasolaryngoscopy and CT
of the neck, both of which were negative. A dental examination
was also normal.
We ordered venous Doppler ultrasonography to reassess the
DVT in our patient’s right tibial vein. It showed an unchanged distal DVT, but the vein appeared compressed by a vascular structure with arterial Doppler flow (Figure 2A, Figure 2B). An abdom­
inal and lower extremity CTA confirmed a right fibular artery
aneurysm (Figure 2C).

What is the next step in management?
a. Observe and repeat CTA of the right leg in 6 weeks
b. Restart anticoagulation therapy with intravenous heparin
c. Surgically excise the aneurysm and ligate the right fibular
artery
d. Proceed with emergent arterial embolization of the right fibular artery
e. Proceed with filter placement in the inferior vena cava

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Figure 2: (A) Transverse view of a right fibular artery aneurysm on 1 cm–scaled ultrasonography. Colour Doppler ultrasonography showing arterial flow within
a 2 cm aneurysm (a). (B) Doppler ultrasonography of the leg showing that the adjacent tibial vein is compressed by the aneurysm and thrombosed distally (v).
(C) Three-dimensional reconstruction of the distal right leg arteries by computed tomography angiography showing a 2 cm aneurysm (a) of the right fibular artery.

The answer is (c). In the context of infective endocarditis, we suspected a mycotic aneurysm of the right fibular artery that ori­
ginated from a septic embolus. Rapid initiation of appropriate
treatment with intravenous antibiotics is essential in controlling
sepsis and lowers the risk of recurrent embolization.1 Prompt
­surgical intervention is required because of the risk of rupture with
potential hemorrhage or loss of limb.6
There is inadequate evidence to suggest endovascular treatment of a peripheral mycotic aneurysm.7 We decided against using
an inferior vena cava filter, given the distal localization of the DVT,
the associated bacteremia and a treatable compressive cause.

Discussion
Our patient was a cancer survivor who was treated for a distal DVT,
which was presumed idiopathic at the time. He subsequently developed infective endocarditis that was complicated by an embolic
stroke and we diagnosed a peripheral mycotic aneurysm adjacent to
the DVT. Persistent fever over weeks is unusual for a treated DVT and
warrants investigation for other causes of fever, including bacter­
emia. Although associated with prosthetic valves, endocarditis
affects native valves in 80% of cases. Our patient’s enterococcal
endocarditis began insidiously. His leukocyte count was within the
reference range, as was found in 53% of patients in a retrospective
cohort study.8 We could not establish the source of infection, as is the
situation for most cases (70%) of enterococcal endocarditis.4
Our patient’s fibular aneurysm was caused by a septic embolus
that created a focus of infection in the fibular artery wall, and it is possible that a small mycotic aneurysm was missed by the first ultra­
sonography. The local infection and inflammation may have caused a
DVT in the contiguous posterior tibial vein. Compression by the growing mycotic aneurysm, as reported in previous case series, could
explain the persistence of the DVT despite anticoagulation treatment.9
Mycotic aneurysm is reported in 2%–4% of cases of infective
endocarditis and arises from septic embolism, most frequently from

mitral valve vegetations.6 Most mycotic aneurysms are caused by
Staphylococcus and Salmonella species but may also be caused by
Streptococcus and Enterococcus species and gram-negative organisms.10 They can affect intracranial, peripheral or thoracoabdominal
arteries.6 Patients often present with an erythematous and painful
pulsatile mass, but other presentations include acute limb ischemia,
constitutional symptoms and coexisting local soft tissue infection.
The AHA mycotic aneurysm guideline recommends Doppler ultrasonography, CTA or both to diagnose peripheral aneurysms.6
Management of peripheral infected aneurysms is mainly surgical.6 Different procedures, such as ligation, excision and in situ
reconstruction, or excision with extra-anatomic revascularization,
are supported by retrospective studies.6 A 2018 study involving
28 patients with peripheral mycotic aneurysms found no difference
in limb-threatening ischemia when comparing revascularization to
resection and ligation only.11 In the absence of randomized prospective data, the AHA advocates for individualized management.6 The
results of a 2017 systematic review involving patients with infected
iliofemoral arterial pseudoaneurysms showed that endovascular
stents for iliofemoral mycotic aneurysms, combined with surgical
débridement, favoured low complication and high patency rates.7
This option might be offered to patients who are at high surgical
risk, although evidence is insufficient to suggest it. Intravenous antibiotics are usually continued up to at least 6 weeks after surgery.6

Case revisited
Our patient underwent resection of the aneurysm with ligation of
the right fibular artery. Collateral tibial arteries were sufficient for
distal perfusion. No intracranial or extracranial aneurysms were
found in a subsequent CTA. Replacement of the mitral valve was
delayed until 4 weeks had passed after t he d iagnosis o f h emorrhagic stroke, in part because of the necessity for anticoagulation treatment during heart surgery. The patient remained
hemodynamically and neurologically stable before and after
the valve replacement, and made a complete recovery.

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References
1. Baddour LM, Wilson WR, Bayer AS, et al.; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on
Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on
Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American
Heart Association. Circulation 2015;132:1435-86.

Competing interests: None declared.

2. Habib G, Lancellotti P, Antunes MJ, et al.; ESC Scientific Document Group. 2015
ESC guidelines for the management of infective endocarditis: the task force for
the management of infective endocarditis of the European Society of Cardiology
(ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS),
the European Association of Nuclear Medicine (EANM). Eur Heart J 2015;36:
3075-128.

Contributors: All of the authors contributed to the conception
and design of the work, drafted the manuscript, revised it crit­
ically for important intellectual content, gave final approval of the
version to be published and agreed to be accountable for all
aspects of the work.

3. Fernández Guerrero ML, Goyenechea A, Verdejo C, et al. Enterococcal endocard­
itis on native and prosthetic valves: a review of clinical and prognostic factors
with emphasis on hospital-acquired infections as a major determinant of outcome. Medicine (Baltimore) 2007;86:363-77.

Content licence: This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NCND 4.0) licence, which permits use, distribution and reproduction in any
medium, provided that the original publication is properly cited, the
use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/
licenses/by-nc-nd/4.0/

4. Pericàs JM, Corredoira J, Moreno A, et al.; Hospital Clínic and Hospital Lucus
Augusti Infective Endocarditis Investigators. Relationship between Enterococcus
faecalis infective endocarditis and colorectal neoplasm: preliminary results from
a cohort of 154 patients. Rev Esp Cardiol (Engl Ed) 2017;70:451-8.
5. van Es N, Le Gal G, Otten H-M, et al. Screening for occult cancer in patients with
unprovoked venous thromboembolism: a systematic review and meta-analysis
of individual patient data. Ann Intern Med 2017;167:410-7.
6. Wilson WR, Bower TC, Creager MA, et al.; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on
Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing;
Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular
Surgery and Anesthesia; Council on Peripheral Vascular Disease; Stroke Council.
Vascular graft infections, mycotic aneurysms, and endovascular infections: a scientific statement from the American Heart Association. Circulation 2016;134:
e412-60.

This article has been peer reviewed.
The authors have obtained patient consent.
Affiliation: Department of Medicine, Faculty of Medicine, Université
Laval, Québec, Que.

Funding: Benoit M.-Labbé is supported by the Quebec Heart and
Lung Institute – Université Laval Chair in Knowledge Translation,
Education and Prevention in Respiratory and Cardiovascular Health.
Alexandre Lafleur is supported by the CMA-MD Educational Leadership Chair in Health Professions Education.
Acknowledgement: The authors thank Dr. André Lamarre, interventional radiologist at CHU de Québec-Université Laval, for his support.
Correspondence to: Benoît M.-Labbé,
benoit.m-labbe@criucpq.ulaval.ca

7. Moulakakis KG, Alexiou VG, Sfyroeras GS, et al. Endovascular management of
infected iliofemoral pseudoaneurysms: a systematic review. Vasa 2017;46:5-9.
8. Wallace SM, Walton BI, Kharbanda RK, et al. Mortality from infective endocard­
itis: clinical predictors of outcome. Heart 2002;88:53-60.
9. Walsh JJ, Williams LR, Driscoll JL, et al. Vein compression by arterial aneurysms.
J Vasc Surg 1988;8:465-9.
10. González I, Sarriá C, López J, et al. Symptomatic peripheral mycotic aneurysms
due to infective endocarditis: a contemporary profile. Medicine (Baltimore)
2014;93:42-52.
11. Salzler GG, Long B, Avgerinos ED, et al. Contemporary results of surgical management of peripheral mycotic aneurysms. Ann Vasc Surg 2018;53:86-91.

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