Keywords
graft infection - aorta -
Aspergillus fumigatus
Introduction
Vascular stent infections caused by Aspergillus fumigatus have rarely been described. Invasive aspergillosis (IA) is the most devastating complication
of Aspergillus-related diseases, targeting severely immunocompromised patients.[1] Aspergillus vascular graft infections are serious complications of vascular surgical
procedures and have been associated with high mortality despite aggressive medical
and surgical interventions. Aspergillosis as a clinical entity is difficult to diagnose,
and is detected often only during microbiological investigations of intraoperative
or postmortem tissue samples.[2]
Case Report
A 60-year-old man with a 6 year history of stent graft implantation (EndoFit 30/200,
LeMaitre Vascular, Burlington, Massachusetts) in the descending aorta due to trauma-induced
descending aneurysm (7 cm diameter) presented with fever, night sweats, and weight
loss over 5 months. He was initially treated with antibiotics by a general practitioner,
which proved unsuccessful. Stress electrocardiogram revealed signs of ischemia and
led the patient to our clinic to exclude coronary artery diseases. Three-vessel coronary
artery diseases with hemodynamic stenosis (left anterior descending [LAD] coronary
artery, right circumflex [LCX], and right coronary artery [RCA]) and impaired left
ventricle-function (ejection fraction [EF] 45%) were found. The patient had leukocytosis
and elevated CRP values. Despite intravenous antibiotic therapy, fever persisted.
Anticoagulation therapy (phenprocoumon) was started due to paroxysmal atrial fibrillation
which was probably triggered by infection. A few days after admission paresthesia
of the left arm was noted and a cerebral hemorrhage was diagnosed ([Fig. 1A]). A chest CT scan showed an attached thrombus, air bubbles, and a suspected abscess
around the stent graft of the descending aorta ([Fig. 1B, C]). Blood cultures remained negative despite an incubation period of 3 weeks. Notably,
the serum immunoglobulin E (IgE) level was strongly elevated (> 1,000 U/mL). Anamnestically,
the patient suffered from a mild form of atopic dermatitis and bronchial asthma. An
inhaled bronchodilator was used as needed. The pulmonary status showed no abnormalities
in the CT image.
Fig. 1 (A) Cerebral hemorrhage, (B and C) abscess around the stent graft of the descending
aorta with attached thrombus and air inclusions, (D) mild inflammatory reaction detected
by SPECT imaging technique, (E) end-to-side anastomosis of ascending aorta and coronary
artery bypass grafting, (F) the correct contrast filling of vascular graft. SPECT,
single-photon emission computed tomography.
A single-photon emission computed tomography (SPECT) and a Positron emission tomography
with 2-deoxy-2-[fluorine-18]fluoro-D-glucose with computed tomography (18F-FDG PET/CT)
did not identify any infection and pathological structure throughout the body. However,
a mild inflammatory reaction in the aneurysmal sac was detected ([Fig. 1D]). Three coronary artery bypass grafting (CABG) and an extra-anatomic ascending-to-descending
aortic bypass (Gelsoft 22 mm, Vascutek, Juchinnan, Scotland, United Kingdom) were
performed. [Fig. 1E] shows the end-to-side anastomosis of the ascending aorta and CABG. A silver Dacron
prosthesis was tunneled to the left pleural space and an end-to-end anastomosis of
the graft prosthesis and the unaffected part of the descending aorta, near to the
thoracoabdominal crossing, was performed. The aorta was ligated at the junction between
aortic arch and descending aorta, close to the origin of the subclavian. The stent
graft was removed in toto. Severe inflammation of the aneurysmal sac was noted. The
infection process extended close to the trachea. A conspicuous whitish material was
thoroughly debrided from the inflamed aneurysmal sac. Microscopical examination of
intraoperative samples revealed fungal hyphae (Gram and stilbene stain). Cultures
yielded the growth of colonies typical for A. fumigatus. These findings were confirmed by polymerase chain reaction analysis.
At the postoperative day 1, the patient was extubated. His response was adequate.
On the 3rd postoperative day, the patient experienced respiratory failure and had
to be reintubated. [Fig. 1F] shows correct contrast-filling of the vascular graft. Several attempts of extubation
failed. Respiratory exhaustion of the patient required peripheral venovenous extracorporeal
membrane oxygenation (ECMO). Sputum-cultures were positive for enterococci. Chest-abdominal
CT scan showed multiorgan microembolization. At postoperative day 10, there was spontaneous
bleeding from the thoracic drainage. A rethoracotomy revealed no bleeding source,
but ubiquitous bleeding which could be tamponaded by stripe towels. Despite maximal
therapy the patient died due to multiorgan failure and septic shock 11 days after
operation. Postmortem pathology revealed primarily severe bacterial pneumonia as the
cause of death.
Discussion
A. fumigatus is a ubiquitous fungus that can invade tissues and cause severe infections, primarily
in immunocompromised individuals. Most often, this fungus is introduced via the respiratory
tract. Vascular graft infections due to A. fumigatus have rarely been reported, even rare if the patient is immunocompetent.[2]
[3]
IA represents a diagnostic and clinical challenge because blood cultures remain almost
always negative and aggressive treatment is required to prevent irreversible complications
and lethal outcome. Excision of the infected prosthetic material and antifungal therapy
should be performed rapidly.
Elevated serum IgE level are characteristic for allergic bronchopulmonary aspergillosis
and atopic dermatitis.[4]
[5] Immunological investigations in our patient revealed elevated IgE levels above 1,000
U/mL. Retrospectively, the asthmatic disease of our patient presumably facilitated
the penetration and invasion of A. fumigatus. The aneurysmal sac infection was very close to the trachea which suggests that the
infection spread via the trachea, although a true fistula was excluded by bronchoscopy.
Interestingly, a left vocal cord paralysis was diagnosed months before the patient's
admission.
From a diagnostic point of view, it is important to note that in our patient samples
of bronchoalveolar lavages remained negative for A. fumigatus and did not contain elevated concentrations of Aspergillus galactomannan antigen.
In the serum, both the levels of anti-Aspergillus antibodies (indirect hemagglutination
test [IHAT] 1:160) and of galactomannan antigen (index 1.0) were inconspicuous. These
unexpected results are consistent with the interpretation that the fungal infection
remained primarily localized between the aneurysm wall and the stent graft.
In conclusion, a fungal late-onset graft infection (e.g., with A. fumigatus) should be suspected in patients with implanted grafts, who suffer from unexplained,
blood culture-negative fever that does not respond to antibiotics and who have a history
of dermatitis or bronchial asthma with elevated IgE antibodies. Serological analyses
for Aspergillus antibodies and galactomannan antigen should always be performed, although negative
results never exclude an Aspergillus infection as illustrated by the present case.
Expeditious antifungal treatment is required to prevent occurrence of irreversible
complications.