Mycotic Iliac Artery Aneurysm Caused by Clostridium difficile in a Patient with Axillobifemoral Bypass for Leriche Syndrome

Abstract

A 74-year old man on hemodialysis developed a mycotic aneurysm caused by Clostridium difficile. To the best of our knowledge, this is only the second case of such an aneurysm reported in the literature. He had previously undergone axillobifemoral bypass grafting because of symptomatic infrarenal aortic stenosis. Although no blood flow was detected in his occluded right common iliac artery, it expanded rapidly despite intensive antibiotic therapy. As the blood supply to the lower limbs was already secured, only resection of the infected arteries was performed.

Introduction

Extra-intestinal Clostridium difficile infection is rare. Although Clostridium septicum aortitis has occasionally been reported in patients with gastrointestinal malignancy,^1,2) to the best of our knowledge there is only one previously reported case of mycotic aneurysm caused by C. difficile.³⁾ We present a patient with C. difficile aortitis who developed a rapidly expanding mycotic aneurysm of the right common iliac artery, which was occluded and had previously been bypassed with an axillobifemoral graft because of symptomatic Leriche syndrome. The mycotic aneurysm was surgically resected.

Case Report

A 74-year-old man with dialysis-dependent chronic renal failure was admitted to our hospital with dyspnea and septic shock due to pneumonia. He had undergone axillobifemoral bypass grafting because of symptomatic occlusion of the infrarenal abdominal aorta (Leriche syndrome) 3 years previously. Twenty-two days before admission, he had undergone surgery for appendicitis with peritonitis. He had an uneventful recovery and had been discharged 7 days later.

Examination at the time of admission showed blood pressure 90/50 mmHg, pulse rate 74 beats/min, and temperature 39.0°C. Laboratory testing showed a decreased neutrophil count of 2830/mm³ and an elevated C-reactive protein (CRP) level of 25.0 mg/dL (normal range ≤0.3 mg/dL). He was treated with intravenous meropenem (0.5 g/day for 2 weeks) and his sepsis resolved. Pseudomonas aeruginosa was grown from blood and sputum cultures. He developed persistent diarrhea, and colonoscopy on day 15 after admission showed pseudomembranous colitis. Stool immunoassay for C. difficile toxin was negative. He was discharged on day 45 after admission.

Twenty-eight days later, he was readmitted because of general fatigue. He had a temperature of 39.1 °C but no abdominal or back pain. His blood pressure was 160/80 mmHg and his pulse rate was 63 beats/min. Laboratory testing showed a normal neutrophil count of 7100/mm³ and an elevated CRP level of 8.8 mg/dL. Computed tomography (CT) revealed expansion of his occluded right common iliac artery to 22 mm in diameter, with surrounding edema (Fig. 1a). As these findings were consistent with a diagnosis of mycotic aneurysm, empirical antibiotic therapy was started with intravenous meropenem (1 g/day) and vancomycin (0.5 g/day). Blood cultures grew no pathogens, but his mild fever continued and his CRP level remained slightly elevated at 4.8 mg/dL on day 6 after readmission. Repeat CT on day 6 after readmission showed an increase in the diameter of the right common iliac artery to 26 mm. Repeat CT on day 18 after readmission showed further expansion of the right common iliac artery to 29 mm (Fig. 1b). We considered that antibiotic therapy would not resolve his infection, and planned surgical resection the following day.

Fig. 1.

(a) Enhanced computed tomography (CT) images at the time of readmission showing an occluded right iliac artery, expanded to 22 mm in diameter, with surrounding edema (white arrow). (b) CT image on day 18 after readmission, showing further expansion of the right iliac artery to 29 mm in diameter, with surrounding edema (black arrow).

Laparotomy through a midline incision revealed a thickened retroperitoneum with inflammatory changes, but no pus, and an aneurysm of the right common iliac artery. Extensive debridement was performed, with excision of the infrarenal abdominal aorta and both common iliac arteries. The resected arteries had thickened walls and were filled with fragile thrombi (Fig. 2). The aortic stump was reinforced with pieces of resected parietal peritoneum and covered with an omental pedicle. Pathological examination of the surgical specimen showed granulation tissue with inflammatory cell infiltration and Gram-positive rods (Fig. 3). Culture of the surgical specimen grew C. difficile.

Fig. 2.

Surgical view showing the aneurysmal right common iliac artery. The resected arteries had thickened walls and were filled with fragile thrombi (open arrow). The aortic stump was reinforced with pieces of resected parietal peritoneum (black arrow).

Fig. 3.

Histological examination showing granulation tissue with inflammatory cell infiltration and Gram-positive rods (white arrows) (hematoxylin and eosin stain, × 200).

On day 5 after aortic surgery, we performed reoperation because of a gradually expanding retroperitoneal hematoma in the left lateral abdominal wall caused by bleeding of the left inferior epigastric artery, which had been injured during resection of the parietal peritoneum. The patient then recovered slowly but uneventfully and was discharged to another hospital for rehabilitation on day 38 after aortic surgery. The cultured C. difficile was sensitive to ampicillin/sulbactam, vancomycin, and minomycin. He was treated with intravenous ampicillin/sulbactam for 3 weeks, followed by oral metronidazole.

Discussion

Mycotic aneurysms have been reported to account for 1.3% of aortic and iliac artery aneurysms.⁴⁾ Such aneurysms are most commonly caused by Staphylococcus and Salmonella spp but may also be caused by anaerobic bacteria.⁵⁾ Mycotic aneurysms caused by Clostridium spp are rare, and to the best of our knowledge, only one mycotic aneurysm caused by C. difficile has previously been reported, although C. septicum aortitis has occasionally been reported.³⁾ A review by Seder et al.¹⁾ found that 91% of patients with C. septicum arteritis also had colonic adenocarcinoma or polyps. They suggested that an anaerobic environment in such rapidly growing tumors is suitable for growth of Clostridium spp and bacteria then disseminate into the systemic circulation and infect atherosclerotic lesions, causing mycotic aneurysms.¹⁾ Although little is known about the pathophysiological mechanisms associated with C. difficile arteritis because of its infrequent occurrence, similarities can be expected with C. septicum arteritis. C. difficile toxins might, therefore, cause mucosal damage resulting in bacteremia.³⁾ A review by Libby et al.⁶⁾ found that all adult patients with C. difficile bacteremia had concomitant gastrointestinal pathology such as diarrhea, small bowel obstruction, or ischemic colitis, which may compromise the integrity of the gastrointestinal tract. They reported that C. difficile bacteremia was strongly associated with prior antibiotic exposure but that there was no significant association between C. difficile arteritis and colonic tumors.⁶⁾ Jacobs et al.⁷⁾ reviewed reported extracolonic C. difficile infections such as osteomyelitis, visceral abscesses, and prosthetic joint infections, and found that transitory C. difficile bacteremia was implicated as a cause of these infections. In our patient, colonoscopy performed after intensive antibiotic therapy for septic shock showed pseudomembranous colitis, which is well known to be caused by C. difficile infection, but stool toxin testing and blood cultures were negative. García-Lechuz et al.⁸⁾ reported that extracolonic C. difficile infection does not always produce toxins, and that blood cultures are rarely positive. In our patient, the atherosclerotic lesions in the occluded arteries, where oxygen delivery and pH were reduced, provided an environment where C. difficile was able to grow and form a mycotic aneurysm. Libby et al.⁶⁾ reported that compromised immunological status was associated with extracolonic C. difficile infection. In our patient, chronic renal failure may have contributed to providing suitable conditions for C. difficile to infect the atherosclerotic lesions.

The 6-month overall mortality rate in patients with mycotic aneurysms caused by C. septicum has been reported to be 64% and 100% in those who did not undergo surgery.¹⁾ In our patient, the mycotic aneurysm formed in a chronically occluded common iliac artery where blood flow was minimal. Contrary to our expectation that expansion of the aneurysm would be controlled by broad-spectrum antibiotics because the intra-arterial pressure was low, the artery increased rapidly in diameter. Postoperative mortality after mycotic aneurysm repair is 33%–63% if the aneurysm has ruptured, compared with 0%–13% if the aneurysm has not ruptured.^4,9) It has, therefore, been suggested that antibiotic therapy alone is insufficient, and surgical treatment is indicated to avoid rupture.

The C. difficile isolated from our patient’s mycotic aneurysm was sensitive to metronidazole and ampicillin/sulbactam. The optimal duration of intensive antibiotic therapy in cases of C. difficile bacteremia or C. septicum aortitis has not been established. As infection may occasionally recur, postoperative antibiotic therapy in patients with C. septicum aortitis should be administered for at least 6–8 weeks as recommended for other mycotic aneurysms, should probably be continued for at least 3 months, and not be discontinued until no further signs of infection are detected.⁴⁾

Conclusion

Mycotic aneurysms caused by C. difficile are rare but may be encountered after gastrointestinal inflammation in patients with atherosclerotic lesions. In our case, bacteremia secondary to pseudomembranous colitis might have caused infection of the occluded arteries, which subsequently developed unexpected expansion in spite of intensive antibiotic therapy.

Disclosure Statement

The authors have no conflicts of interest to declare.