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Acute Graft Thrombosis and Aortic Root Pseudoaneurysm Associated With Listeria Bacteremia: A Case Report and Review of the Literature

Oehler, Richard L. MD, FACP*; Elko, Lucinda M. MD, Rph; Gompf, Sandra G. MD*

Infectious Diseases in Clinical Practice: November 2004 - Volume 12 - Issue 6 - p 345-349
doi: 10.1097/01.idc.0000144905.89192.d8
Case Reports and Reviews: Case Report
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Abstract: Listeria monocytogenes is an increasingly recognized cause of human diseases, especially in the immunocompromised host. Vascular infections involving Listeria remain relatively rare. In addition, Listeria vascular infections and Listeria endocarditis appear to be slightly different entities. We report the case of a 50-year-old man with steroid-dependent systemic lupus erythematosis who presented with Listeria bacteremia occurring with acute axillobifemoral graft thrombosis and an aortic root pseudoaneurysm. Following thrombectomy and graft revision, the patient was successfully treated with a 6-week course of intravenous antibiotics.

The authors review Listeria vascular infections published to date and compare them with L. monocytogenes endocarditis cases published in the literature. Only 18 Listeria vascular infections have been previously reported. Major risk factors include age over 50 years, arteriosclerosis, hypertension, and diabetes. Most cases can be managed with surgical resection and/or graft revision followed by extended antibiotic therapy. Ampicillin or trimethoprim-sulfamethoxazole are the drugs of choice in treating these infections.

*James A. Haley Veterans Administration Hospital, Tampa, FL and Department of Internal Medicine, University of South Florida College of Medicine, Tampa, FL and †Department of Internal Medicine Division of Infectious Diseases, University of South Carolina School of Medicine, Columbia, SC.

Address correspondence and reprint requests to Richard L. Oehler, MD, FACP, James A. Haley Veterans Administration Medical Center, 13,000 Bruce B. Downs Boulevard, #111J, Tampa, FL 33612. E-mail: Richard.oehler@med.va.gov.

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CASE PRESENTATION

A 50-year-old African-American male presented to the Emergency Department with the acute onset of fever, nausea, vomiting, diarrhea, right lower extremity tenderness, and numbness. He was experiencing pain in his right lateral upper leg with parasthesias below the knee. That morning, he had awakened and noticed local discomfort and swelling at his right lateral tibial area.

The patient's past medical history was significant for systemic lupus erythematosis with associated renal and cerebrovascular involvement. He was chronically steroid-dependent. The patient also had sickle cell trait and anemia with a history of congestive heart failure with an ejection fraction of 25-30%. He denied tobacco and ethanol use. He had received an abdominal aortic aneurysm repair in 1993 and a right axillobifemoral bypass and thrombectomy in 2000. He was married and was a nonsmoker and nondrinker.

The man did not recall any specific environmental or dietary exposures in the prior month. He frequently patronized a specific Mexican-style fast food restaurant and recalls ordering a burrito there on the previous day. He occasionally dined at another fast-food chicken restaurant but mostly had hot meals prepared at home by his spouse and mother. He avoided most cold foods and dairy products.

Physical examination revealed a cachectic 50-year-old black male lying in an emergency room bed. Vital signs on admission were significant for a fever of 101.3°F. Blood pressure was 91/52 mm Hg and pulse was 107 beats per minute. Respirations were 18 breaths per minute. No nuchal rigidity was apparent. His lungs were clear bilaterally. He was tachycardic but had no cardiac murmurs. The abdominal examination was benign. He had a left above the knee amputation. The right lower extremity examination showed mottling of the right foot and coolness of the foot to the ankle level. The patient reported decreased sensation below the knee with weakness of the entire right lower extremity, noted to be worse distally. Doppler studies of the right lower extremity showed absent right popliteal, dorsalis pedis, and posterior tibial pulses. A biphasic pulse was preserved in the axillobifemoral graft to approximately the groin area.

Laboratory studies showed a normal leukocyte count of 7.3 g/L and a hemoglobin of 8.7 g/dL. The patient was hyponatremic with a serum sodium of 132 mEq/L. Blood urea nitrogen was 23 mg/dL. The creatinine was 1.5 mg/dL. Transaminases were normal. The alkaline phosphatase was 166 U/L. The international normalized ratio was 1.45, and the activated partial thromboplastin time was 29.4 seconds. Admission chest x-ray showed no acute infiltrates.

The patient was taken emergently to surgery and was found to have an occluded right axillobifemoral bypass graft. He received a right axillobifemoral bypass graft thrombectomy with revision of the right femoral anastomosis and right calf fasciotomy. The patient was also found postoperatively to have a pseudoaneurysm of the ascending aorta with residual thrombus by perioperative thoracic CT. Blood cultures obtained at admission were positive for Listeria monocytogenes and coagulase-negative staphylococci in 2/2 sets. Graft material submitted for histopathology showed rare Gram-negative cocci. (See Discussion). Cultures of the thrombus material were not performed. Postoperatively, the patient was started on vancomycin, ampicillin, and gentamicin. Coronary angiogram performed on the tenth postoperative day further identified the aortic root pseudoaneurysm with associated involvement of the left main and proximal right coronary artery. Surgical intervention to repair the pseudoaneurysm was deferred because the patient was felt to be at excessively high risk for this procedure.

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DISCUSSION

Listeria monocytogenes is an increasingly recognized cause of human disease in several risk groups, including pregnant women, neonates, the elderly, transplant recipients receiving immunosuppressants, and others with impaired cell-mediated immunity. It is the only Listeria species that infects humans. The organism is a nonsporulating, facultatively anaerobic, catalase-positive, oxidase-negative, Gram-positive rod that grows well on blood agar, displaying β-hemolysis.1,2 In clinical specimens, the organisms may appear Gram-variable and can resemble diphtheroids, cocci, or diplococci.1 A flagellated organism, the bacterium displays tumbling motility at 28°C. Listeria favors a temperature range of 30-37°C but can also grow preferentially to other bacteria at refrigerator temperatures (4-10°C).2

Listeriosis tends to occur sporadically but can also be seen in outbreaks. While typically being associated with central nervous system infection (meningitis and meningoencephalitis), L. monocytogenes has also been reported with sepsis, brain abscess,3 endophthalmitis,4 cholecystitis,5 liver abscess,6 and osteomyelitis.7 Vascular infections involving Listeria are less well characterized. Aneurysm involvement with Listeria has been previously reported in just 18 cases worldwide.8-21 More frequently, case reports of Listeria endocarditis have appeared in the literature,22-26 suggesting its affinity for vascular tissues.

Mycotic arterial aneurysms are extremely rare but can have substantial morbidity and mortality. Infected prosthetic grafts have been reported to occur with a frequency of 1.5-6%.15,18 Graft infection occurring shortly after surgery is usually due to implantation of exogenous organisms at the time of the procedure. Late graft infection, as was believed to be the case in our patient, can occur months or years after surgery and can be due to seeding of the graft following an episode of bacteremia.15

We analyzed 18 cases of Listeria-associated arterial infections reported in the literature, including 7 recent cases occurring since an initial reported series by Gauto et al16 (see Tables 1 and 2). The mean age was 65 years. (median = 74 years). Approximately 89% of individuals were 50 years of age or greater. Major risk factors for Listeria-associated vascular disease included atherosclerosis (44%), hypertension (22%), and diabetes (16.7%). A third of the infections were associated with vascular grafts. Abdominal computed tomography (CT) scanning was performed in 8 (44%) of 18 cases. Blood cultures were positive for Listeria in only 28% of the patients. Fever was a common presenting sign, affecting 83% of individuals. Local pain occurred more commonly than the presence of a palpable mass (50% versus 29%, respectively). Endocarditis was rarely associated with Listeria vascular infections, occurring in only 1 (5.5%) case out of 18 reviewed. None of our patients had artificial valves or a history of rheumatic fever, perhaps making the incidence of endocarditis less. Direct mortality across all cases was 27.8%.

TABLE 1

TABLE 1

TABLE 2

TABLE 2

In contrast, the Listeria endocarditis case series published by Spyrou26 revealed a mean age of 53 years (N = 58). There was an overall mortality of 37% associated with the diagnosis. Mortality was higher in patients with prosthetic valves than with those having native valves at 41% versus 31%, respectively. Major endocarditis risk factors included having a prosthetic valve, malignancy, rheumatic heart disease/fever, coronary artery disease (CAD), and diabetes. Unfortunately, blood cultures were not documented in these patients. However, in the 1988 case series by Gallagher25 2 of 3 of patients had persistently positive blood cultures, and 59% of bacteremias were associated with a subacute bacterial endocarditis.25 Interestingly, in Gauto's series,16 only 1 of 44 patients had an associated mycotic aneurysm. In comparing Listeria vascular infections with Listeria endocarditis, a few points are obvious (Table 3). Listeria vascular infections are chiefly a disease of the elderly, with almost 90% occurring above the age of 50 years. Listeria endocarditis tends to more commonly affect younger age groups, with a mean age in a prior published series of only 53 years. The mortality rate in Listeria vascular infections is somewhat more modest at 33% versus 37% overall with endocarditis. Perhaps the history of prior rheumatic heart disease in the endocarditis group selects for earlier onset and more aggressive disease. The most significant risk factor for Listeria endocarditis is a prosthetic valve, whereas for Listeria vascular infections, it appears to be atherosclerosis. Lastly, blood cultures are positive in only about a quarter of cases of Listeria vascular infections, in contrast to endocarditis where the incidence is much higher.25

TABLE 3

TABLE 3

The time of onset of the aortic root pseudoaneurysm in our patient is not completely clear, but the patient had undergone a transthoracic echocardiogram approximately 15 months earlier that did not show this finding. A transesophageal echocardiogram (Fig. 1) was performed 2 to 3 weeks postthrombectomy. In addition to the pseudoaneurysm, it showed normal valvular pathology and no evidence of endocarditis. Because only pathologic specimens were collected at the time of thrombectomy, in situ culture confirmation of L. monocytogenes could not be done. However, Gram-negative cocci were seen within the graft material and may have represented Listeria organisms with an atypical morphology. For future cases, Listeria can be detected in tissue by PCR-based tests.2 Our surgical colleagues felt that the patient would be at extremely high risk for further surgical intervention and so invasive biopsy specimens from the aorta could not be obtained. However, we feel that the simultaneous onset of Listeria bacteremia and acute graft thrombosis in the setting of a newly diagnosed aortic root pseudoaneurysm implies a strong and direct association. Risk factors for listeriosis in our patient likely included chronic steroid use and systemic lupus erythromatosis.

FIGURE 1

FIGURE 1

Ampicillin is generally regarded as the antibiotic agent of choice for most Listeria infections. For purposes of synergy seen in vitro and in animal models, many authorities suggest adding gentamicin to ampicillin for Listeria bacteremia in patients with immunocompromised status and for those with Listeria meningitis and endocarditis.1 For penicillin-allergic patients, trimethoprim-sulfamethoxazole is thought to be the most effective alternative single agent.1 However, as ampicillin and trimethoprim/sulfa have different mechanisms of action, clinicians may consider using ampicillin and trimethoprim/sulfa together as this may offer a better outcome than either one used alone. A 6-week course of antimicrobial therapy has generally been administered in prior cases of vascular infection.16,20,21 Following the thrombectomy, our patient successfully completed a 42-day course of vancomycin (for coverage of coagulase negative staphylococci) plus ampicillin while in a long-term facility. At 6 weeks post-treatment, blood cultures were negative, and the patient and his vascular implants were clinically stable with no evidence of a recurrent thrombosis or infection. However, within 4 months of the original diagnosis, the pseudoaneurysm began to enlarge in size (Fig. 2), and the patient developed an obstructed left main stem bronchus due to compression from the aneurysm. Although no evidence of recurrent Listeria infection was found, he ultimately succumbed to a postobstructive pneumonia.

FIGURE 2

FIGURE 2

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