- Email: [email protected]
Salmonella Mycotic Thoracoabdominal Aortic Aneurysm Associated With Chronic Lymphocytic Leukemia
Salmonella Mycotic Thoracoabdominal Aortic Aneurysm Associated With Chronic Lymphocytic Leukemia Michal Tomek,1 Nicholas J.W. Cheshire,1,2 Nung Rudarakanchana,1,2 Dunisha Samarasinghe,3 and Colin D. Bicknell,1,2 London, United Kingdom
Non-typhoidal Salmonella infections typically cause self-limiting gastroenteritis. However, extraintestinal focal infections, including mycotic aneurysms of the aorta, can also occur. We present the case of a 71-year-old man with chronic lymphocytic leukemia (CLL) and a large type V thoracoabdominal mycotic aneurysm infected with Salmonella enteritidis, complicated by thoracolumbar spondylodiscitis, paravertebral collections, and epidural abscess. This is the first report of Salmonella aortitis in the setting of CLL, and the unusual extent of local infective invasion seen here with Salmonella enteritidis infection raises a suspicion of CLL-related immunosuppression as a direct predisposing factor. This case illustrates the need to consider the possibility of an immune defect, even in CLL patients with normal leukocyte counts. The underlying mechanisms are unclear, but are likely to involve defects in cell-mediated immunity, thought to be of particular importance in invasive infections with intracellular pathogens such as Salmonella spp.
INTRODUCTION Infections with non-typhoidal Salmonella organisms are common worldwide. Although most cases remain limited to the gastrointestinal tract, transient bacteremia is present in 2e8% of patients.1 Extraintestinal focal infections also occur, most commonly affecting bones, joints, and arteries2; the risk of endothelial infection is estimated at 9e25% in patients >50 years of age with Salmonella bacteremia.3 This report was part funded by the NIHR through the Comprehensive Biomedical Research Centre. 1 Imperial Vascular Unit, St. Mary’s Hospital, Imperial College London, London, UK.
Extraintestinal salmonellosis is more likely to occur in immunocompromised individuals.4 We describe the presentation and treatment of an unusual case of a patient with chronic lymphocytic leukemia (CLL) and a large type V saccular thoracoabdominal aortic aneurysm infected with Salmonella enteritidis, complicated by thoracolumbar spondylodiscitis, paravertebral collections, and epidural abscess. To our knowledge, this is the first documented case of a Salmonella-infected aortic aneurysm with these extensive complications in the setting of CLL.
CASE REPORT
2
Department of Surgery and Cancer, Imperial College London, London, UK. 3
Department of Microbiology, St. Mary’s Hospital, Imperial College London, London, UK. Correspondence to: Nung Rudarakanchana, PhD, Department of Surgery and Cancer, Imperial College London, St. Mary’s Hospital, 1003, 10th Floor QEQM, South Wharf Road, London W2 1NY, UK; E-mail: [email protected] Ann Vasc Surg 2013; 27: 1186.e17e1186.e21 http://dx.doi.org/10.1016/j.avsg.2012.11.013 Ó 2013 Elsevier Inc. All rights reserved. Manuscript received: August 24, 2012; manuscript accepted: November 16, 2012; published online: August 26, 2013.
A 71-year-old man with CLL presented with a 6-week history of constitutional symptoms and low back pain. Two months previously, while on a trip to Bahrain, he suffered a bout of gastroenteritis that resolved within a few days. Subsequently, he developed low-grade fever and generalized fatigue. He also noticed worsening night sweats, as well as deterioration of his chronic low back pain. Three weeks prior to presentation at our center he had been briefly admitted to another hospital, where his blood cultures grew Salmonella. He was discharged home on oral 1186.e17
1186.e18 Case reports
Annals of Vascular Surgery
Fig. 1. (A) Axial contrast-enhanced computerized tomography of the abdomen. (B) Three-dimensional volume-rendered reconstruction of the aortogram. A lobulated suprarenal aortic lesion is demonstrated, suggestive of a mycotic aneurysm.
amoxicillin and erythromycin after resolution of his fever, although repeat blood cultures were not done at this time. His past medical history included prostate cancer (stage T2a), successfully treated with radical radiotherapy, 8 years earlier, and CLL (Binet classification stage A), diagnosed 10 months before presentation. Regarding the CLL, the patient had occasional night sweats and at the time of presentation had persistent lymphadenopathy involving <3 lymph node areas (1e2-cm lymph nodes in the supraclavicular and axillary areas bilaterally), but no hepatomegaly or splenomegaly and no other complications of CLL. He was otherwise fit with well-controlled hypertension, and had no long-term intravenous access ports or lines. On admission the patient was clinically septic. His white cell count was 9.5 109/L (neutrophil count 5.7 109/L, lymphocyte count 3.7 109/L), and Creactive protein 110 mg/L. Admission blood cultures grew Salmonella enteritidis and this was confirmed on repeated blood cultures on days 3, 8, and 10. He was started on intravenous ceftriaxone for Salmonella bacteremia. He tested negative for human immunodeficiency virus (HIV). Echocardiography did not show evidence of infective endocarditis, but computerized tomography (CT) scan revealed the presence of a type V thoracoabdominal aortic aneurysm (Fig. 1). This extended from the distal thoracic aorta to the level of the renal arteries and measured 7.6 cm in maximum diameter, with appearances typical of a mycotic aneurysm. Retroperitoneal and mesenteric lymphadenopathy was also present, presumed secondary to CLL. There was no prior imaging for comparison, and we were unable to ascertain whether the aortic lesion had arisen de novo or represented a superinfected aneurysm. Given his history of back pain, magnetic resonance imaging (MRI) of the spine was subsequently performed; this demonstrated vertebral body osteomyelitis and discitis extending from T11 to L2, contiguous with the aneurysmal aorta (Fig. 2). There were small abscesses noted within the left psoas muscle, and a small
ventral epidural abscess at the L1e2 level, with thecal compression. There was, however, no clinical indication of spinal cord compression. After 2 weeks of intravenous antibiotic administration, to reduce the systemic bacteremia and risk of immediate graft colonization, as well as to allow for adequate preoperative planning and preparation, the patient underwent an open aneurysm repair through a thoracolaparotomy incision. The proximal clamp was placed in the midthoracic aortic segment and repair with a rifampicin-soaked Dacron graft was undertaken from the lower thoracic to infrarenal aorta with side-branch grafts to the superior mesenteric and renal arteries. The aortic wall was very thin and friable throughout the aneurysmal segment. The thrombus within the aneurysm sac was removed and the anterior and lateral walls of the aortic sac debrided and irrigated thoroughly. A spinal drain was placed as standard. The risk of infection was thought to be low, as the drain was placed in the lower lumbar spinal canal, significantly lower than the epidural abscess. The drain was placed at 10e15 cm above the spinal cord with the patient flat and left in situ for 3 days. The presence of Salmonella genus DNA was detected from biopsies of the aneurysm wall by polymerase chain reaction (PCR) analysis. Regarding management of the spinal disease, the possibility of surgical management was also considered; however, given the absence of any neurologic compromise and no evidence of spinal instability, in discussion with the spinal surgeons we elected to continue with conservative management. The patient recovered well postoperatively. He remained on a combination of intravenous ceftriaxone and azithromycin for 6 weeks after the surgery, and was discharged with a plan for life-long azithromycin therapy. In terms of follow-up, the presence of recurrent infection is being monitored by a combination of clinical review, regular leukocyte counts, and C-reactive protein blood analysis. The patient remains well without sign of overt infection or complications from discitis/epidural abscess at 6 months. Follow-up MRI scans of the spine
Vol. 27, No. 8, November 2013
Case reports 1186.e19
Fig. 2. (A) T1-weighted contrast-enhanced and (B) T2-weighted sagittal magnetic resonance imaging showing the lobulated aortic aneurysm with contiguous abnormal signal and enhancement within vertebral bodies extending from T11 to L2. The intervening disks
at these levels also show signal change. At L1e2 there is a ventral epidural abscess (arrow), which results in compression of the thecal sac. The changes are consistent with a mycotic aneurysm of the aorta with associated spondylodiscitis and infective paravertebral involvement.
have revealed gradual resolution of abscess cavity, and CT examination is scheduled for 1 year postoperatively.
aneurysms arise in the infrarenal aorta, and suprarenal mycotic aneurysms are extremely rare; just over a dozen cases of thoracoabdominal aneurysms associated with Salmonella have been documented prior to this report. Although the reason for the predominance of infrarenal location among cases of Salmonella aortitis is not entirely clear, it may reflect the commonly involved mechanism of infective seeding to a preexisting abdominal aortic aneurysm, as the latter is most frequently found in the infrarenal aorta. The extent of contiguous spread of the infection seen here was also unusual. Although spondylodiscitis and psoas muscle involvement in the setting of Salmonella enteritidis aneurysm have been reported in a few cases,12e14 the association with an epidural abscess has not been described previously. The extensiveness of the infective process observed in this case, unusual for Salmonella enteritidis infections, as well as the absence of any of the classical risk factors, were suggestive of underlying immunosuppression. We postulate that the CLL, with associated immunosuppression, was the primary predisposing condition for this patient’s extensive infective disease. Two other reports of Salmonella aortitis associated with a hematologic malignancy have been published to date: One such case involved a patient with an aneurysm of the ascending thoracic aorta infected with Salmonella typhimurium in the setting of myelodysplastic syndrome4; the other involved a patient with abdominal aortic aneurysm due to non-typhoidal
DISCUSSION One to 2% of abdominal aortic aneurysms are associated with infection, of which about a third are due to Salmonella spp5; the majority of these involve Salmonella typhimurium or Salmonella enteritidis.4 The most common etiology of mycotic aneurysm formation is hematogenous seeding of the aortic wall. Occasionally, infection of the aorta can arise through contiguous spread from an adjacent septic focus, or by direct inoculation during surgery or trauma.6 Mycotic aneurysms typically occur in the setting of significant underlying comorbidities; given that atherosclerotic disease of the aorta predisposes to infective seeding of the endothelium, common risk factors include advanced age, diabetes mellitus, and hypertension.7,8 Immunosuppression increases the risk of both Salmonella bacteremia and focal arterial infection,9,10 and non-typhoidal Salmonella aneurysms have been associated with human immunodeficiency virus (HIV), liver disease, autoimmune disorders, malignancy, renal transplant, and long-term corticosteroid treatment.4,11 Herein we have presented a case of a large thoracoabdominal mycotic aneurysm infected with Salmonella enteritidis in a patient with CLL, complicated by spondylodiscitis, paravertebral collections, and epidural abscess. Most Salmonella-infected
1186.e20 Case reports
Salmonella in association with multiple myeloma.15 The case presented here is the first described in the setting of CLL. Although the etiology of immunosuppression in CLL is commonly therapy-related, inherent defects in both humoral and cell-mediated immunity also occur. The patient described herein received no treatment for the CLL and his immunoglobulin levels were normal. Consequently, it may be that a disorder of cell-mediated immunity resulted in an increased susceptibility to bacteremia and invasive Salmonella infection. Cell-mediated immunity is known to be of particular importance in infections with Salmonella spp, which are facultative intracellular pathogens. Mechanisms underlying the immune defect are unclear but may involve helper T-cell dysfunction, abnormalities in neutrophil chemotaxis, or phagocytic enzyme deficiencies.16e18 Management of mycotic aortic aneurysms consists of a combination of surgical and antimicrobial treatment. Although antibiotic therapy does improve survival, mycotic aneurysms managed with medical treatment alone are almost invariably fatal.4 Surgical intervention typically involves resection of the aneurysmal segment and debridement of the infected periaortic tissue with subsequent revascularization, classically with extra-anatomical bypass. In aortic aneurysms involving the visceral segment, direct open repair may be necessary, with bypasses from the main aortic graft to the visceral vessels, making thorough debridement and continued antibiotic therapy of utmost importance.19 The most appropriate choice of graft material in mycotic aneurysm repair remains a matter of debate; rifampicin-soaked grafts, silverimpregnated grafts, and arterial and venous homografts have all been successfully used in this setting. Although in situ replacement with homografts has been shown to be highly effective,20 their limited availability can pose a problem in emergency situations. The rifampicin-soaked Dacron grafts represent an effective alternative and are used frequently; whereas rifampicin targets gram-positive staphylococci as its primary antimicrobial mode of action, the high concentrations of the eluted drug are also thought to be effective in protecting the graft from gram-negative bacilli.21 Where visceral vessels are included in the thoracoabdominal aortic aneurysm (TAAA), open surgical repair options include using a multibranched graft with anastomoses to each viscera, taking multiple visceral branches on an aortic patch and anastomosing this to the main graft, or debranching with bypasses to native vessels, such as iliacs. Successful endoluminal stenting has also been reported for aortic and peripheral infected
Annals of Vascular Surgery
aneurysms,22e24 but data on the long-term outcomes of this approach are lacking; its use does not allow for a complete debridement of the infected arterial and perivascular tissues, thus increasing the risk of graft infection. In our case we considered direct anatomic repair as the best option, given the delays associated with custom-made graft design for endoluminal repair. Of note, a hybrid endoluminal/surgical repair was not possible due to the extensive retroperitoneal lymphadenopathy. In conclusion, we have presented the first report of aortic salmonellosis in the setting of CLL, complicated by severe local extension of the infective disease. This case suggests that CLL may act as a direct predisposing factor for focal invasive arterial infection with Salmonella, even in patients with normal leukocyte counts. Salmonella-infected aneurysms carry a poor prognosis and early diagnosis with prompt surgical intervention is essential. However, as reported here and in other cases, the commonly nonspecific presentation of mycotic aneurysms can pose a diagnostic challenge, leading to potentially catastrophic delays.25,26 Therefore, we urge clinicians to maintain a high index of suspicion in any patient with Salmonella bacteremia of unknown etiology, even in the absence of any history of vascular disease or classical vascular risk factors. The possibility of an underlying immunosuppressive disorder, including malignancy, should be considered in such patients, especially if florid manifestations of invasive Salmonella infection are found.
REFERENCES 1. Nielsen H, Gradel KO, Schønheyder HC. High incidence of intravascular focus in nontyphoid Salmonella bacteremia in the age group above 50 years: a population-based study. APMIS 2006;114:641e5. 2. Chen PL, Chang CM, Wu CJ, et al. Extraintestinal focal infections in adults with nontyphoid Salmonella bacteraemia: predisposing factors and clinical outcome. J Intern Med 2007;261:91e100. 3. Cohen PS, O’Brien TF, Schoenbaum SC, et al. The risk of endothelial infection in adults with salmonella bacteremia. Ann Intern Med 1978;89:931e2. 4. Soravia-Dunand VA, Loo VG, Salit IE. Aortitis due to Salmonella: report of 10 cases and comprehensive review of the literature. Clin Infect Dis 1999;29:862e8. 5. Sommerville RL, Allen EV, Edwards JE. Bland and infected arteriosclerotic abdominal aortic aneurysms: a clinicopathologic study. Medicine (Baltimore) 1959;38:207e21. 6. McHenry MC, Rehm SJ, Krajewski LP, et al. Vertebral osteomyelitis and aortic lesions: case report and review. Rev Infect Dis 1991;13:1184e94. 7. Wang JH, Liu YC, Yen MY, et al. Mycotic aneurysm due to non-typhy salmonella: report of 16 cases. Clin Infect Dis 1996;23:743e7.
Vol. 27, No. 8, November 2013
8. Fern andez Guerrero ML, Aguado JM, Arribas A, et al. The spectrum of cardiovascular infections due to Salmonella enterica: a review of clinical features and factors determining outcome. Medicine (Baltimore) 2004;83:123e38. 9. Samra Y, Shaked Y, Maier MK. Nontyphoid salmonellosis in renal transplant recipients: report of five cases and review of the literature. Rev Infect Dis 1986;8:431e40. 10. Ramos JM, Garcia-Corbeira P, Aguado JM, et al. Classifying extraintestinal non-typhoid Salmonella infections. Q J Med 1996;89:123e6. 11. Hsu RB, Tsay YG, Wang SS, et al. Management of aortic aneurysm infected with Salmonella. Br J Surg 2003;90: 1080e4. 12. Bowling TE, Baron JH. An unusual Salmonella infection. J R Soc Med 1992;85:106e7. 13. Carson BJ, McEwan AJ, Hoskinson ME, et al. Detection of an abdominal mycotic aneurysm on three-phase bone scan. A case report. Clin Nucl Med 1995;20:267e9. 14. Learch TJ, Sakamoto B, Ling AC, et al. Salmonella spondylodiscitis associated with a mycotic abdominal aortic aneurysm and paravertebral abscess. Emerg Radiol 2009;16: 147e50. 15. Munoz J, Namo S, Stoltenberg M, Chapman R. Salmonellarelated mycotic aortic aneurysm heralding a diagnosis of multiple myeloma. Am J Hematol 2012;87:820e1. 16. Chiorazzi N, Fu SM, Montazeri G, et al. T cell helper defect in patients with chronic lymphocytic leukemia. J Immunol 1979;122:1087e90. 17. Zeya HI, Keku E, Richards F 2nd, et al. Monocyte and granulocyte defect in chronic lymphocytic leukemia. Am J Pathol 1979;95:43e54.
Case reports 1186.e21
18. Itala M, Vainio O, Remes K. Functional abnormalities in granulocytes predict susceptibility to bacterial infections in chronic lymphocytic leukaemia. Eur J Haematol 1996;57: 46e53. 19. Pasic M, Carrel T, Tonz P, et al. Mycotic aneurysm of the abdominal aorta: extra-anatomic versus in situ reconstruction. Cardiovasc Surg 1993;1:48e52. 20. Knosalla C, Weng Y, Yankah AC, et al. Using aortic allograft material to treat mycotic aneurysms of the thoracic aorta. Ann Thorac Surg 1996;61:1146e52. 21. Lachapelle K, Graham AM, Symes JF. Antibacterial activity, antibiotic retention, and infection resistance of a rifampinimpregnated gelatin-sealed Dacron graft. J Vasc Surg 1994;19:675e82. 22. Stoica L, Chocron S, Falcoz PE, et al. Endovascular stent grafting for contained rupture of the descending thoracic aorta. Eur J Cardiothor Surg 2003;23:1068e70. 23. Koeppel TA, Gahlen J, Diehl S, et al. Mycotic aneurysm of the abdominal aorta with retroperitoneal abscess: successful endovascular repair. J Vasc Surg 2004;40:164e6. 24. Riga C, Bicknell C, Jindal R, et al. Endovascular stenting of peripheral infected aneurysms: a temporary measure or a definitive solution in high-risk patients. Cardiovasc Intervent Radiol 2008;31:1228e35. 25. Wong SP, Lai TK, Ng WL, et al. Non-typhoid Salmonella mycotic aneurysm of the aortic arch. Hong Kong Med J 2007;13:234e7. 26. Kaneko K, Nonomura Y, Watanabe K, et al. Infected abdominal aortic aneurysm caused by nontyphoid Salmonella in an immunocompromised patient with rheumatoid arthritis. J Infect Chemother 2009;15:312e5.
Non-typhoidal Salmonella infections typically cause self-limiting gastroenteritis. However, extraintestinal focal infections, including mycotic aneurysms of the aorta, can also occur. We present the case of a 71-year-old man with chronic lymphocytic leukemia (CLL) and a large type V thoracoabdominal mycotic aneurysm infected with Salmonella enteritidis, complicated by thoracolumbar spondylodiscitis, paravertebral collections, and epidural abscess. This is the first report of Salmonella aortitis in the setting of CLL, and the unusual extent of local infective invasion seen here with Salmonella enteritidis infection raises a suspicion of CLL-related immunosuppression as a direct predisposing factor. This case illustrates the need to consider the possibility of an immune defect, even in CLL patients with normal leukocyte counts. The underlying mechanisms are unclear, but are likely to involve defects in cell-mediated immunity, thought to be of particular importance in invasive infections with intracellular pathogens such as Salmonella spp.
INTRODUCTION Infections with non-typhoidal Salmonella organisms are common worldwide. Although most cases remain limited to the gastrointestinal tract, transient bacteremia is present in 2e8% of patients.1 Extraintestinal focal infections also occur, most commonly affecting bones, joints, and arteries2; the risk of endothelial infection is estimated at 9e25% in patients >50 years of age with Salmonella bacteremia.3 This report was part funded by the NIHR through the Comprehensive Biomedical Research Centre. 1 Imperial Vascular Unit, St. Mary’s Hospital, Imperial College London, London, UK.
Extraintestinal salmonellosis is more likely to occur in immunocompromised individuals.4 We describe the presentation and treatment of an unusual case of a patient with chronic lymphocytic leukemia (CLL) and a large type V saccular thoracoabdominal aortic aneurysm infected with Salmonella enteritidis, complicated by thoracolumbar spondylodiscitis, paravertebral collections, and epidural abscess. To our knowledge, this is the first documented case of a Salmonella-infected aortic aneurysm with these extensive complications in the setting of CLL.
CASE REPORT
2
Department of Surgery and Cancer, Imperial College London, London, UK. 3
Department of Microbiology, St. Mary’s Hospital, Imperial College London, London, UK. Correspondence to: Nung Rudarakanchana, PhD, Department of Surgery and Cancer, Imperial College London, St. Mary’s Hospital, 1003, 10th Floor QEQM, South Wharf Road, London W2 1NY, UK; E-mail: [email protected] Ann Vasc Surg 2013; 27: 1186.e17e1186.e21 http://dx.doi.org/10.1016/j.avsg.2012.11.013 Ó 2013 Elsevier Inc. All rights reserved. Manuscript received: August 24, 2012; manuscript accepted: November 16, 2012; published online: August 26, 2013.
A 71-year-old man with CLL presented with a 6-week history of constitutional symptoms and low back pain. Two months previously, while on a trip to Bahrain, he suffered a bout of gastroenteritis that resolved within a few days. Subsequently, he developed low-grade fever and generalized fatigue. He also noticed worsening night sweats, as well as deterioration of his chronic low back pain. Three weeks prior to presentation at our center he had been briefly admitted to another hospital, where his blood cultures grew Salmonella. He was discharged home on oral 1186.e17
1186.e18 Case reports
Annals of Vascular Surgery
Fig. 1. (A) Axial contrast-enhanced computerized tomography of the abdomen. (B) Three-dimensional volume-rendered reconstruction of the aortogram. A lobulated suprarenal aortic lesion is demonstrated, suggestive of a mycotic aneurysm.
amoxicillin and erythromycin after resolution of his fever, although repeat blood cultures were not done at this time. His past medical history included prostate cancer (stage T2a), successfully treated with radical radiotherapy, 8 years earlier, and CLL (Binet classification stage A), diagnosed 10 months before presentation. Regarding the CLL, the patient had occasional night sweats and at the time of presentation had persistent lymphadenopathy involving <3 lymph node areas (1e2-cm lymph nodes in the supraclavicular and axillary areas bilaterally), but no hepatomegaly or splenomegaly and no other complications of CLL. He was otherwise fit with well-controlled hypertension, and had no long-term intravenous access ports or lines. On admission the patient was clinically septic. His white cell count was 9.5 109/L (neutrophil count 5.7 109/L, lymphocyte count 3.7 109/L), and Creactive protein 110 mg/L. Admission blood cultures grew Salmonella enteritidis and this was confirmed on repeated blood cultures on days 3, 8, and 10. He was started on intravenous ceftriaxone for Salmonella bacteremia. He tested negative for human immunodeficiency virus (HIV). Echocardiography did not show evidence of infective endocarditis, but computerized tomography (CT) scan revealed the presence of a type V thoracoabdominal aortic aneurysm (Fig. 1). This extended from the distal thoracic aorta to the level of the renal arteries and measured 7.6 cm in maximum diameter, with appearances typical of a mycotic aneurysm. Retroperitoneal and mesenteric lymphadenopathy was also present, presumed secondary to CLL. There was no prior imaging for comparison, and we were unable to ascertain whether the aortic lesion had arisen de novo or represented a superinfected aneurysm. Given his history of back pain, magnetic resonance imaging (MRI) of the spine was subsequently performed; this demonstrated vertebral body osteomyelitis and discitis extending from T11 to L2, contiguous with the aneurysmal aorta (Fig. 2). There were small abscesses noted within the left psoas muscle, and a small
ventral epidural abscess at the L1e2 level, with thecal compression. There was, however, no clinical indication of spinal cord compression. After 2 weeks of intravenous antibiotic administration, to reduce the systemic bacteremia and risk of immediate graft colonization, as well as to allow for adequate preoperative planning and preparation, the patient underwent an open aneurysm repair through a thoracolaparotomy incision. The proximal clamp was placed in the midthoracic aortic segment and repair with a rifampicin-soaked Dacron graft was undertaken from the lower thoracic to infrarenal aorta with side-branch grafts to the superior mesenteric and renal arteries. The aortic wall was very thin and friable throughout the aneurysmal segment. The thrombus within the aneurysm sac was removed and the anterior and lateral walls of the aortic sac debrided and irrigated thoroughly. A spinal drain was placed as standard. The risk of infection was thought to be low, as the drain was placed in the lower lumbar spinal canal, significantly lower than the epidural abscess. The drain was placed at 10e15 cm above the spinal cord with the patient flat and left in situ for 3 days. The presence of Salmonella genus DNA was detected from biopsies of the aneurysm wall by polymerase chain reaction (PCR) analysis. Regarding management of the spinal disease, the possibility of surgical management was also considered; however, given the absence of any neurologic compromise and no evidence of spinal instability, in discussion with the spinal surgeons we elected to continue with conservative management. The patient recovered well postoperatively. He remained on a combination of intravenous ceftriaxone and azithromycin for 6 weeks after the surgery, and was discharged with a plan for life-long azithromycin therapy. In terms of follow-up, the presence of recurrent infection is being monitored by a combination of clinical review, regular leukocyte counts, and C-reactive protein blood analysis. The patient remains well without sign of overt infection or complications from discitis/epidural abscess at 6 months. Follow-up MRI scans of the spine
Vol. 27, No. 8, November 2013
Case reports 1186.e19
Fig. 2. (A) T1-weighted contrast-enhanced and (B) T2-weighted sagittal magnetic resonance imaging showing the lobulated aortic aneurysm with contiguous abnormal signal and enhancement within vertebral bodies extending from T11 to L2. The intervening disks
at these levels also show signal change. At L1e2 there is a ventral epidural abscess (arrow), which results in compression of the thecal sac. The changes are consistent with a mycotic aneurysm of the aorta with associated spondylodiscitis and infective paravertebral involvement.
have revealed gradual resolution of abscess cavity, and CT examination is scheduled for 1 year postoperatively.
aneurysms arise in the infrarenal aorta, and suprarenal mycotic aneurysms are extremely rare; just over a dozen cases of thoracoabdominal aneurysms associated with Salmonella have been documented prior to this report. Although the reason for the predominance of infrarenal location among cases of Salmonella aortitis is not entirely clear, it may reflect the commonly involved mechanism of infective seeding to a preexisting abdominal aortic aneurysm, as the latter is most frequently found in the infrarenal aorta. The extent of contiguous spread of the infection seen here was also unusual. Although spondylodiscitis and psoas muscle involvement in the setting of Salmonella enteritidis aneurysm have been reported in a few cases,12e14 the association with an epidural abscess has not been described previously. The extensiveness of the infective process observed in this case, unusual for Salmonella enteritidis infections, as well as the absence of any of the classical risk factors, were suggestive of underlying immunosuppression. We postulate that the CLL, with associated immunosuppression, was the primary predisposing condition for this patient’s extensive infective disease. Two other reports of Salmonella aortitis associated with a hematologic malignancy have been published to date: One such case involved a patient with an aneurysm of the ascending thoracic aorta infected with Salmonella typhimurium in the setting of myelodysplastic syndrome4; the other involved a patient with abdominal aortic aneurysm due to non-typhoidal
DISCUSSION One to 2% of abdominal aortic aneurysms are associated with infection, of which about a third are due to Salmonella spp5; the majority of these involve Salmonella typhimurium or Salmonella enteritidis.4 The most common etiology of mycotic aneurysm formation is hematogenous seeding of the aortic wall. Occasionally, infection of the aorta can arise through contiguous spread from an adjacent septic focus, or by direct inoculation during surgery or trauma.6 Mycotic aneurysms typically occur in the setting of significant underlying comorbidities; given that atherosclerotic disease of the aorta predisposes to infective seeding of the endothelium, common risk factors include advanced age, diabetes mellitus, and hypertension.7,8 Immunosuppression increases the risk of both Salmonella bacteremia and focal arterial infection,9,10 and non-typhoidal Salmonella aneurysms have been associated with human immunodeficiency virus (HIV), liver disease, autoimmune disorders, malignancy, renal transplant, and long-term corticosteroid treatment.4,11 Herein we have presented a case of a large thoracoabdominal mycotic aneurysm infected with Salmonella enteritidis in a patient with CLL, complicated by spondylodiscitis, paravertebral collections, and epidural abscess. Most Salmonella-infected
1186.e20 Case reports
Salmonella in association with multiple myeloma.15 The case presented here is the first described in the setting of CLL. Although the etiology of immunosuppression in CLL is commonly therapy-related, inherent defects in both humoral and cell-mediated immunity also occur. The patient described herein received no treatment for the CLL and his immunoglobulin levels were normal. Consequently, it may be that a disorder of cell-mediated immunity resulted in an increased susceptibility to bacteremia and invasive Salmonella infection. Cell-mediated immunity is known to be of particular importance in infections with Salmonella spp, which are facultative intracellular pathogens. Mechanisms underlying the immune defect are unclear but may involve helper T-cell dysfunction, abnormalities in neutrophil chemotaxis, or phagocytic enzyme deficiencies.16e18 Management of mycotic aortic aneurysms consists of a combination of surgical and antimicrobial treatment. Although antibiotic therapy does improve survival, mycotic aneurysms managed with medical treatment alone are almost invariably fatal.4 Surgical intervention typically involves resection of the aneurysmal segment and debridement of the infected periaortic tissue with subsequent revascularization, classically with extra-anatomical bypass. In aortic aneurysms involving the visceral segment, direct open repair may be necessary, with bypasses from the main aortic graft to the visceral vessels, making thorough debridement and continued antibiotic therapy of utmost importance.19 The most appropriate choice of graft material in mycotic aneurysm repair remains a matter of debate; rifampicin-soaked grafts, silverimpregnated grafts, and arterial and venous homografts have all been successfully used in this setting. Although in situ replacement with homografts has been shown to be highly effective,20 their limited availability can pose a problem in emergency situations. The rifampicin-soaked Dacron grafts represent an effective alternative and are used frequently; whereas rifampicin targets gram-positive staphylococci as its primary antimicrobial mode of action, the high concentrations of the eluted drug are also thought to be effective in protecting the graft from gram-negative bacilli.21 Where visceral vessels are included in the thoracoabdominal aortic aneurysm (TAAA), open surgical repair options include using a multibranched graft with anastomoses to each viscera, taking multiple visceral branches on an aortic patch and anastomosing this to the main graft, or debranching with bypasses to native vessels, such as iliacs. Successful endoluminal stenting has also been reported for aortic and peripheral infected
Annals of Vascular Surgery
aneurysms,22e24 but data on the long-term outcomes of this approach are lacking; its use does not allow for a complete debridement of the infected arterial and perivascular tissues, thus increasing the risk of graft infection. In our case we considered direct anatomic repair as the best option, given the delays associated with custom-made graft design for endoluminal repair. Of note, a hybrid endoluminal/surgical repair was not possible due to the extensive retroperitoneal lymphadenopathy. In conclusion, we have presented the first report of aortic salmonellosis in the setting of CLL, complicated by severe local extension of the infective disease. This case suggests that CLL may act as a direct predisposing factor for focal invasive arterial infection with Salmonella, even in patients with normal leukocyte counts. Salmonella-infected aneurysms carry a poor prognosis and early diagnosis with prompt surgical intervention is essential. However, as reported here and in other cases, the commonly nonspecific presentation of mycotic aneurysms can pose a diagnostic challenge, leading to potentially catastrophic delays.25,26 Therefore, we urge clinicians to maintain a high index of suspicion in any patient with Salmonella bacteremia of unknown etiology, even in the absence of any history of vascular disease or classical vascular risk factors. The possibility of an underlying immunosuppressive disorder, including malignancy, should be considered in such patients, especially if florid manifestations of invasive Salmonella infection are found.
REFERENCES 1. Nielsen H, Gradel KO, Schønheyder HC. High incidence of intravascular focus in nontyphoid Salmonella bacteremia in the age group above 50 years: a population-based study. APMIS 2006;114:641e5. 2. Chen PL, Chang CM, Wu CJ, et al. Extraintestinal focal infections in adults with nontyphoid Salmonella bacteraemia: predisposing factors and clinical outcome. J Intern Med 2007;261:91e100. 3. Cohen PS, O’Brien TF, Schoenbaum SC, et al. The risk of endothelial infection in adults with salmonella bacteremia. Ann Intern Med 1978;89:931e2. 4. Soravia-Dunand VA, Loo VG, Salit IE. Aortitis due to Salmonella: report of 10 cases and comprehensive review of the literature. Clin Infect Dis 1999;29:862e8. 5. Sommerville RL, Allen EV, Edwards JE. Bland and infected arteriosclerotic abdominal aortic aneurysms: a clinicopathologic study. Medicine (Baltimore) 1959;38:207e21. 6. McHenry MC, Rehm SJ, Krajewski LP, et al. Vertebral osteomyelitis and aortic lesions: case report and review. Rev Infect Dis 1991;13:1184e94. 7. Wang JH, Liu YC, Yen MY, et al. Mycotic aneurysm due to non-typhy salmonella: report of 16 cases. Clin Infect Dis 1996;23:743e7.
Vol. 27, No. 8, November 2013
8. Fern andez Guerrero ML, Aguado JM, Arribas A, et al. The spectrum of cardiovascular infections due to Salmonella enterica: a review of clinical features and factors determining outcome. Medicine (Baltimore) 2004;83:123e38. 9. Samra Y, Shaked Y, Maier MK. Nontyphoid salmonellosis in renal transplant recipients: report of five cases and review of the literature. Rev Infect Dis 1986;8:431e40. 10. Ramos JM, Garcia-Corbeira P, Aguado JM, et al. Classifying extraintestinal non-typhoid Salmonella infections. Q J Med 1996;89:123e6. 11. Hsu RB, Tsay YG, Wang SS, et al. Management of aortic aneurysm infected with Salmonella. Br J Surg 2003;90: 1080e4. 12. Bowling TE, Baron JH. An unusual Salmonella infection. J R Soc Med 1992;85:106e7. 13. Carson BJ, McEwan AJ, Hoskinson ME, et al. Detection of an abdominal mycotic aneurysm on three-phase bone scan. A case report. Clin Nucl Med 1995;20:267e9. 14. Learch TJ, Sakamoto B, Ling AC, et al. Salmonella spondylodiscitis associated with a mycotic abdominal aortic aneurysm and paravertebral abscess. Emerg Radiol 2009;16: 147e50. 15. Munoz J, Namo S, Stoltenberg M, Chapman R. Salmonellarelated mycotic aortic aneurysm heralding a diagnosis of multiple myeloma. Am J Hematol 2012;87:820e1. 16. Chiorazzi N, Fu SM, Montazeri G, et al. T cell helper defect in patients with chronic lymphocytic leukemia. J Immunol 1979;122:1087e90. 17. Zeya HI, Keku E, Richards F 2nd, et al. Monocyte and granulocyte defect in chronic lymphocytic leukemia. Am J Pathol 1979;95:43e54.
Case reports 1186.e21
18. Itala M, Vainio O, Remes K. Functional abnormalities in granulocytes predict susceptibility to bacterial infections in chronic lymphocytic leukaemia. Eur J Haematol 1996;57: 46e53. 19. Pasic M, Carrel T, Tonz P, et al. Mycotic aneurysm of the abdominal aorta: extra-anatomic versus in situ reconstruction. Cardiovasc Surg 1993;1:48e52. 20. Knosalla C, Weng Y, Yankah AC, et al. Using aortic allograft material to treat mycotic aneurysms of the thoracic aorta. Ann Thorac Surg 1996;61:1146e52. 21. Lachapelle K, Graham AM, Symes JF. Antibacterial activity, antibiotic retention, and infection resistance of a rifampinimpregnated gelatin-sealed Dacron graft. J Vasc Surg 1994;19:675e82. 22. Stoica L, Chocron S, Falcoz PE, et al. Endovascular stent grafting for contained rupture of the descending thoracic aorta. Eur J Cardiothor Surg 2003;23:1068e70. 23. Koeppel TA, Gahlen J, Diehl S, et al. Mycotic aneurysm of the abdominal aorta with retroperitoneal abscess: successful endovascular repair. J Vasc Surg 2004;40:164e6. 24. Riga C, Bicknell C, Jindal R, et al. Endovascular stenting of peripheral infected aneurysms: a temporary measure or a definitive solution in high-risk patients. Cardiovasc Intervent Radiol 2008;31:1228e35. 25. Wong SP, Lai TK, Ng WL, et al. Non-typhoid Salmonella mycotic aneurysm of the aortic arch. Hong Kong Med J 2007;13:234e7. 26. Kaneko K, Nonomura Y, Watanabe K, et al. Infected abdominal aortic aneurysm caused by nontyphoid Salmonella in an immunocompromised patient with rheumatoid arthritis. J Infect Chemother 2009;15:312e5.