Selective medical treatment of infected aneurysms of the aorta in high risk patients
Article Outline
Background
Infected aneurysm of the aorta is almost always fatal without undergoing aortic resection. Medical treatment was attempted selectively in patients who were considered too high risk for surgery. We review our experience with 22 patients treated without undergoing aortic resection over 12 years.
Methods
Retrospective chart review.
Results
Between 1995 and 2007, 22 cases of infected aortic aneurysms treated without undergoing aortic resection during the first admission were included. There were 17 men with a median age of 76 years (range, 35 to 88 years). Of 18 pathogens isolated, the most common responsible microorganism was nontyphoid Salmonella in 11 followed by Staphylococcus aureus in five. The site of infection was thoracic in eight and abdominal in 14. The hospital mortality rate was 50%, and the aneurysm-related mortality rate after long-term follow-up was 59%. The event-free survival rate at one year was 32%. Of 11 patients with Salmonella infection, eight patients have lived beyond 30 days and six were event-free after one year. Of 11 patients with non-Salmonella, four patients have lived beyond 30 days and only one was event-free after one year. The overall aneurysm-related mortality rate was 36% in Salmonella infected patients and 82% in non-Salmonella infected patients.
Conclusion
Clinical results of medical treatment using current antibiotics in patients with infected aortic aneurysm were poor. Traditional surgical excision of infected aortic aneurysms with revascularization remains the gold standard and should be attempted except in high risk patients.
An infected aneurysm of the aorta and adjacent arteries is a rare but life-threatening condition.1, 2, 3, 4, 5, 6, 7 Early diagnosis, more potent antibiotics, and timely surgical intervention have resulted in improved outcome over the last two decades.1, 2, 3, 4, 5, 6, 7 The hospital mortality rates of combined medical and surgical treatment ranged from 16% to 44%.1, 2, 3, 4, 5, 6, 7 The clinical outcome is especially poor in patients with infection caused by nontyphoid Salmonella.8, 9, 10, 11 There were almost no hospital survivors if such patients were treated medically without undergoing aortic resection.11, 12, 13 Infected aortic aneurysm is common in Taiwan and Hong Kong.14, 15, 16, 17, 18, 19 We have reported that death from rupture in patients treated medically without undergoing aortic resection is likely but not inevitable.17 However, only 11 cases were reported then. Here, we review our experience in 22 patients treated without undergoing aortic resection over 12 years. This current report includes the previously reported 11cases.
Patients and methods
Setting
National Taiwan University Hospital (Taipei, Taiwan) is a 2200-bed tertiary care hospital. It serves an urban population of two million persons as both a first-line and tertiary care facility. It serves also as a referral center for other hospitals in the country with a population of 22 million persons.
Patients
The study patients were obtained from a retrospective analysis of the clinical data for patients with infected aneurysms of the aorta from September 1995 to September 2007. Patients treated without undergoing aortic resection during the first admission were included in this study. In the same time period, 64 patients were treated conventionally with surgical resection as well as antibiotics.
Diagnosis
Clinically, an infected aortic aneurysm was usually preceded by infected aorta or aortitis. Infected aorta was diagnosed with clinical evidence of infection (fever and leukocytosis) and periaortic soft tissue infiltration demonstrated by imaging study with either computed tomography or magnetic resonance imaging.20 Blood culture was used to define the responsible micro-organism.
Medical treatment
As described previously,16, 17 intravenous antibiotic was given once the diagnosed was confirmed. For patients with Salmonella species infections, intravenous ceftriaxone (1000-2000 gm every 12 hours) was used. For patients with non-salmonella infections, antibiotic was based on culture result and sensitivity test. Antibiotics were administered intravenously in the hospital for at least six to eight weeks and until the clinical and laboratory parameters (fever, white cell count, and C-reactive protein) were normalized. Antibiotic was continued orally after discharge. Imaging studies were repeated three to six months after discharge.
Data collection
Data on age, sex, medical co-morbidities, location of infected aneurysms, and clinical outcome were collected retrospectively from the medical records. Aneurysm-related mortality was defined as mortality caused by persistent infection, aneurysm rupture, or unexplained death within one year after the diagnosis of infected aneurysm. The event-free survival was defined as patients who survived and were free from aneurysm-related operations.
Results
Patient characteristics
From 1995 to 2007, 22 patients with infected aortic aneurysms were treated without undergoing aortic resection during the first hospital admission. Patient demographics are shown in Table I. There were 17 men and five women with median age of 76 years (range, 35 to 88 years). The medical co-morbidities included hypertension in eight patients, diabetes mellitus in seven, coronary artery disease in three, end-stage renal disease with regular hemodialysis in four, liver cirrhosis in four, malignancy in two, and chronic obstructive pulmonary disease, pulmonary tuberculosis, human immunodeficiency virus infection, infective endocarditis, and rheumatoid arthritis in one each.
Table I. Patient data of infected aneurysm of the thoracic aorta treated without aortic resection
| No. | Gender | Age in years | Pathogen | Imaging finding | Type of antibiotic | Reason for no operation | Hospital outcome | Late outcome |
|---|---|---|---|---|---|---|---|---|
| 1 | M | 88 | Salmonella, typhimurium | Descending thoracic aorta, pseudoaneurysm 4.5 cm | Ceftriaxone | Old age | Died after 5 days, aneurysm rupture | |
| 7 | M | 70 | Salmonella choleraesuis | Distal aortic arch, infected aorta | Ciprofloxacin | Co-morbidity | Alive | Died after 22 months, bladder carcinoma |
| 8 | M | 80 | Mycobacterium tuberculosis | Descending thoracic aorta, pseudoaneurysm 6 cm | Isoniazid, ethambutol, plus rifampin | Old age | Alive | Died after 2 months, sudden death |
| 9 | M | 49 | Salmonella choleraesuis | Distal aortic arch, pseudoaneurysm 5 cm | Ceftriaxone then ciprofloxacin | Co-morbidity | Alive | Alive after 80 months |
| 15 | M | 83 | Staphylococcus aureus | Descending thoracic aorta, pseudoaneurysm 5 cm | Oxacillin | Old age, co-morbidity | Died after 11 days, aneurysm rupture | |
| 21 | M | 82 | Unknown | Distal aortic arch, pseudoaneurysm 2.3 cm | Ceftriaxone | Old age, co-morbidity | Died after 1 day, GI bleeding | |
| 22 | M | 75 | Unknown | Descending thoracic aorta, pseudoaneurysm 4.4 cm | Ceftriaxone | Co-morbidity | Died after 19 days, aneurysm rupture | |
| 23 | F | 84 | Staphylococcus aureus | Distal aortic arch, pseudoaneurysm 4.1 cm | Vancomycin | Old age, co-morbidity | Died after 44 days, sepsis |
Of the 22 patients, 19 patients were febrile at presentation and 10 patients had localized chest or back pain. None was in shock at the time of presentation. Hemoptysis was present in one patient with an infected aneurysm within the thoracic cavity, and a consciousness disturbance was present in two patients. The initial imaging findings were aortic pseudoaneurysm or saccular aneurysm in 20 patients, fusiform aneurysm in one, and infected aortitis in one. The size of pseudoaneurysm ranged from 2.2 to 12 cm in maximal diameter. The site of infection was the aortic arch in four patients, the descending thoracic aorta in four, the suprarenal abdominal aorta in six, the infrarenal abdominal aorta in six, and the iliac artery in two (Table I, Table II).
Table II. Patient data of infected aneurysm of the abdominal aorta and adjacent arteries treated without aortic resection
| No. | Gender | Age in years | Pathogen | Imaging finding | Type of antibiotic | Reason for no operation | Hospital outcome | Late outcome |
|---|---|---|---|---|---|---|---|---|
| 2 | M | 77 | Staphylococcus aureus | Infrarenal abdominal aorta, pseudoaneurysm 3 cm | Ticarcillin with clavulanic acid plus amikacin | Co-morbidity | Died after 1 day aneurysm rupture | |
| 3 | M | 69 | Unknown | Infrarenal abdominal aorta, fusiform aneurysm 8 cm | Ceftriaxone | Patient preference | Alive | Died after 15 days, aneurysm rupture |
| 4 | F | 35 | Salmonella choleraesuis | Suprarenal abdominal aorta, pseudoaneurysm 4.5 cm | Ceftriaxone then ciprofloxacin | Co-morbidity | Alive | Aneurysm rupture and grafting after 8 years |
| 5 | F | 82 | Escherichia coli | Infrarenal abdominal aorta, pseudoaneurysm 4 cm | Cefazolin | Old age, co-morbidity | Died after 4 days, aneurysm rupture | |
| 6 | F | 55 | Salmonella | Infrarenal abdominal aorta, pseudoaneurysm 3 cm | Ceftriaxone then ciprofloxacin | Patient preference | Alive | Alive after 8 years |
| 10 | M | 83 | Salmonella choleraesuis | Infrarenal abdominal aorta, pseudoaneurysm 4 cm | Ceftriaxone | Old age | Died after 17 days, aneurysm rupture | |
| 11 | M | 86 | Salmonella enteritidis | Suprarenal abdominal aorta, pseudoaneurysm 5.5 cm | Ceftriaxone | Old age | Died after 11 days, aneurysm rupture | |
| 12 | M | 88 | Staphylococcus aureus | Suprarenal abdominal aorta, pseudoaneurysm 6 cm | Teicoplanin plus flomoxef | Old age | Died after 40 days, aneurysm rupture | |
| 14 | M | 76 | Salmonella, typhimurium | Suprarenal abdominal aorta, pseudoaneurysm 4 cm | Cefotaxime then ciprofloxacin | Co-morbidity | Alive | Died after 21 months, heart failure |
| 16 | M | 75 | Salmonella choleraesuis | Iliac artery, pseudoaneurysm 2.2 cm | Ceftriaxone then ciprofloxacin | Co-morbidity | Alive | Alive after 35 months |
| 17 | M | 59 | Salmonella enteritidis | Suprarenal abdominal aorta, pseudoaneurysm 5.6 cm | Ceftriaxone then Co-trimoxazole | Patient preference | Alive | Aneurysm expansion and grafting after 6 months |
| 18 | M | 83 | Unknown | Suprarenal abdominal aorta, pseudoaneurysm 3 cm | Ceftriaxone then ciprofloxacin | Old age | Alive | Died after 17 months, organ failure |
| 19 | M | 38 | Salmonella enteritidis | Iliac artery, pseudoaneurysm 12 cm | Ceftriaxone then ciprofloxacin | Co-morbidity | Died after 8 months GI bleeding | |
| 20 | F | 55 | Staphylococcus aureus | Infrarenal abdominal aorta, pseudoaneurysm 2 cm | Vancomycin | Co-morbidity | Alive | Aneurysm expansion and grafting after 3 months |
Microbiology
All but four patients had a positive blood culture. Of the 18 isolates, the 11 most common responsible microorganism was nontyphoid Salmonella in 11 patients (61%), followed by Staphylococcus aureus in five (28%), Escherichia coli in one, and Mycobacterium tuberculosis in one. The serotypes of isolated nontyphoid Salmonellas were Salmonella cholerasuis in five patients, Salmonella enteritidis in five, Salmonella typhimurium in two, and unknown serotype in one (Table I, Table II). All isolates of nontyphoid Salmonella were sensitive to ceftriaxone and ciprofloxacin.
Management
Once the diagnosis was confirmed, open surgical repair was advised in all patients. However, operation was refused by the patients because of old age in 10 patients, severe medical co-morbidities in 13, or simply patient's preference in three (Table I, Table II). Furthermore, most of these patients were deemed to be unlikely to survive resection surgery and to be at risk for a high rate of postoperative complications because of old age and medical co-morbidity.
Aneurysm location and clinical outcome were summarized in the Fig. There were eight patients with infection within the thoracic cavity: the aortic arch in four patients and the descending thoracic aorta in four (Table I). Of the four patients with infected aortic arch aneurysms, two patients died of aneurysm rupture. There was one late death after 22 months because of an advanced bladder carcinoma. Of the four patients with infected descending thoracic aortic aneurysms, three patients died of aneurysm rupture, and one patient died suddenly at home. There were 14 patients with aortic infection within the abdominal cavity; six infections of the suprarenal abdominal aorta, six of the infrarenal abdominal aorta, and two of an iliac artery (Table II). Of the six patients with infected suprarenal abdominal aortic aneurysms, two patients died of aneurysm rupture. One patient with systemic lupus erythematosus and thrombocytopenia underwent a successful emergency aortic grafting after eight years because of aneurysm rupture. One patient underwent a successful aortic grafting after six months because of aneurysm expansion. There were two late deaths. Of the six patients with infected infrarenal abdominal aortic aneurysms, four patients died of aneurysm rupture. Of the two patients with infected iliac artery aneurysms, one patient with human immunodeficiency virus infection died after eight months of aneurysm rupture and massive gastrointestinal bleeding.
Fig.
Infected aneurysm of the aorta and adjacent arteries: aneurysm location and clinical outcome in 22 patients treated without undergoing aortic resection during the first admission.
Overall, in the 22 patients treated medically without undergoing aortic resection, the in-hospital mortality rate was 50% (11 of 22), and the aneurysm-related mortality rate after long-term follow-up was 59% (13 of 22). The event-free survival rate at one year was 32% (seven of 22). Of seven patients who were event-free after one year, six patients had infection caused by nontyphoid Salmonella. Of the seven patients having a successful medical treatment, the antibiotic regimen was intravenous ceftriaxone followed by oral ciprofloxacin in four patients, intravenous cefotaxime followed by ciprofloxacin in one, ciprofloxacin alone in one and intravenous ceftriaxone followed by oral co-trimoxazole in 1 (Table I, Table II).
Salmonella infection
Of the 22 patients in this series, 11 patients (50%) had infection caused by nontyphoid Salmonella and the impact of Salmonella infection on clinical outcomes is shown in Table III. Of 11 patients with Salmonella infection, eight patients had abdominal infection, while six of 11 patients with infection caused by organisms other than Salmonella had abdominal infection. Eight patients with Salmonella infection (73%) have lived beyond 30 days and six (55%) were event-free after one year. In contrast, of 11 patients with non-Salmonella infections, four patients have lived beyond 30 days and only one (9%) was event-free after one year. Thus, the overall aneurysm-related mortality rate was 36% in Salmonella infected patients and 82% in non-Salmonella infected patients.
Table III. Salmonella infection and clinical outcomes in infected aneurysm of the aorta and adjacent arteries treated without undergoing aortic resection
| Variables | Salmonella | Non-Salmonella |
|---|---|---|
| Abdominal infection | 73% (8/11) | 55%(6/11) |
| Event-free survival at one year | 55%(6/11) | 9%(1/11) |
| Aneurysm-related mortality | 36%(4/11) | 82%(9/11) |
Discussion
Infected aneurysm of the aorta and adjacent arteries is historically a deadly disease with high mortality and morbidity and the anatomic location of the aortic sepsis, the virulence of the infecting organism, and the severity of infection are the important factors affecting prognosis.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 The successful resolution of these uncommon but not rare aortic lesions relates directly to early diagnosis, administration of specific systemic antibiotics, and timely surgical intervention. The surgical intervention includes extensive aortic resection and vascular reconstruction. Previous studies have focused mainly on the results of combined medical and open surgical treatment,1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 and there have been almost no hospital survivors if patients were treated medically without undergoing aortic resection.11, 12, 13 In this current series of 22 patients treated medically without undergoing aortic resection, the prognosis was not uniformly fatal but the results did not match our reported survival after open surgical repair.16, 17
Salmonella infection
In western countries, the most common responsible organisms for infected aortic aneurysms are Staphylococcus aureus and Streptococcus species.1, 2, 3, 4, 5, 6, 7, 8, 9, 10 In contrast, in Taiwan, nontyphoid Salmonella is the most common pathogen.14, 15, 16, 17, 18, 19 It has been reported that aneurysms infected with Gram negative organisms exhibit a greater tendency toward early rupture than those with gram positive organisms and are thus associated with a higher mortality.11 Delay in making the diagnosis adversely affects the death rate. Treated with antibiotics alone, infected aneurysms due to salmonella have been reported to be almost uniformly fatal and until 1976, only four survivors were known in the literature.10, 21, 22, 23 Use of medical therapy alone was also fatal in three patients described in a previous Taiwanese series of 16 patients with pathologically documented Salmonella aortitis.15 Although data from previous studies are limited, the prognosis with medical therapy alone is grim, even with use of third generation cephalosporin.
However, the prognosis of infected aneurysm caused by nontyphoid Salmonella has significantly improved in the last two decades. In this current series, there were 11 patients with infected aortic aneurysms caused by nontyphoid Salmonella and the prognosis of infection caused by nontyphoid Salmonella was not dismal. Furthermore, the prognosis of infected aneurysms caused by nontyphoid Salmonella was much better than that of non-Salmonella infected cases with none of them being event-free beyond one year. Therefore, it is recommended that patients with infected aortic aneurysm caused by micro-organisms other than nontyphoid Salmonella should undergo open surgical repair regardless of the surgical risks. In contrast, in Salmonella-infected patients who refuse operation because of high surgical risks, we recommend the use of intravenous ceftriaxone for four to six weeks followed by life-long oral ciprofloxacin, as about half of them will survive after one year. However, the emergence of ciprofloxacin resistance could be a threat,24, 25 and further studies are needed on the choice of life-long oral antibiotic in ciprofloxacin-resistant nontyphoid Salmonella infection.
Study limitation
The major limitations of this study are a retrospective study design and a long time span. Because of retrospective study design, there was no consistent approach to these patients and the decision for open surgical repair was also variable. However, this study is the largest case series of infected aortic aneurysm treated medically without undergoing aortic resection and provides useful information in management of high-risk patients.
In conclusion, clinical results of medical treatment using current antibiotics in patients with infected aortic aneurysm are still poor. However, the prognosis is not dismal in nontyphoid Salmonella infected patients. In contrast, patients with infection caused by micro-organisms other than nontyphoid Salmonella should undergo early surgical repair.
Author contributions
References
- . Mycotic aneurysms of the thoracic and abdominal aorta and iliac arteries: experience with anatomic and extra-anatomic repair in 33 cases. J Vasc Surg. 2001;33:106–113
- . Surgical outcome of infectious aneurysm of the abdominal aorta with or without SIRS. Cardiovasc Surg. 2001;9:436–440
- Surgical treatment of infected aortic aneurysm. Am J Surg. 1998;175:396–399
- . Mycotic aneurysm of the abdominal aorta: extra-anatomic versus in situ reconstruction. Cardiovasc Surg. 1993;1:48–52
- . Surgical mortality in patients with infected aortic aneurysms. J Am Coll Surg. 2003;196:435–441
- Infected aortic aneurysms: aggressive presentation, complicated early outcome, but durable results. J Vasc Surg. 2001;34:900–908
- Surgical treatment of infected thoracic and abdominal aortic aneurysms. Cardiovasc Surg. 1996;4:476–479
- . Experience with infected aneurysms of the abdominal aorta. Arch Surg. 1975;110:1281–1286
- . Infected aneurysms of the infrarenal abdominal aorta: diagnostic criteria and therapeutic strategy. Ann Vasc Surg. 1997;11:453–463
- . Aortitis due to Salmonella: report of 10 cases and comprehensive review of the literature. Clin Infect Dis. 1999;29:862–868
- . Bacteriologic and surgical determinants of survival in patients with mycotic aneurysms. J Vasc Surg. 1984;1:541–547
- . Salmonella infections of the abdominal aorta. Surg Gynecol Obstet. 1992;175:102–106
- . Salmonella mycotic aneurysm of the aortic arch: case report and review. Clin Infect Dis. 1995;21:523–528
- . Salmonellosis and mycotic aneurysm of the aorta (A report of 10 cases). J Infect. 1995;30:129–133
- Mycotic aneurysm due to non-typhi salmonella: report of 16 cases. Clin Infect Dis. 1996;23:743–747
- . Surgical treatment for primary infected aneurysm of descending thoracic aorta, abdominal aorta and iliac arteries. J Vasc Surg. 2002;36:746–750
- . Infected aortic aneurysms: clinical outcome and risk factor analysis. J Vasc Surg. 2004;40:30–35
- . In situ reconstruction of septic aortic 16 pseudoaneurysm due to Salmonella or Streptococcus microbial aortitis: long-term follow-up. J Vasc Surg. 2003;38:975–982
- . Surgical treatment of infected aneurysms and pseudoaneurysms of the thoracic and abdominal aorta. Am J Surg. 2005;189:150–154
- . Infected aortic aneurysms: imaging findings. Radiology. 2004;231:250–257
- . Nontyphoidal salmonellosis. Clin Infect Dis. 2001;32:263–269
- . The spectrum of cardiovascular infections due to Salmonella enterica: a review of clinical features and factors determining outcome. Medicine. 2004;83:123–138
- Extraintestinal infection by group C Salmonella: a case report and review of the literature. Hepatogastroenterology. 2001;48:471–474
- . Antimicrobial drug resistance in salmonella-infected aortic aneurysms. Ann Thorac Surg. 2005;80:530–536
- The emergence in Taiwan of fluoroquinolone resistance in Salmonella enterica serotype choleraesuis. N Engl J Med. 2002;346:413–419
Competition of interest: none.
PII: S0741-5214(08)01332-3
doi:10.1016/j.jvs.2008.08.004
© 2009 The Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
