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A hazard of immunosuppression: Aspergillus niger infection of abdominal aortic aneurysm
Eur J VascSurg 8, 369-371 (1994)
CASE REPORT A Hazard of Immunosuppression" A pergillus Abdominal Aortic Aneurysm
niger Infection of
F. C. T. Smith 1, E. Rees 2, T. S. J. Elliott 2 and C. P. Shearman I
University Departments of 1Surgery and 2Clinical Microbiology, Queen Elizabeth Hospital, Edgbaston, Birmingham, U.K.
Introduction We report the case of a female patient taking oral steroids who was found to have a true mycotic abdominal aortic aneurysm infected with Aspergillus niger. This illustrates a further hazard of steroid therapy and underlines the importance of establishing a diagnosis prior to their long term use. Aetiology and management of the case are discussed, and the importance of routine culture and microscopy of aneurysm contents in potentially immunosuppressed patients is emphasised.
Case Report A 74-year-old female was referred by her GP for surgical assessment of an asymptomatic abdominal aortic aneurysm found on routine clinical examination. She had chronic obstructive airways disease which had been treated with inhaled salbutamol and terbutaline for 5 years. One year previously she had been commenced on 4mg prednisolone daily for a presumptive diagnosis of temporal arteritis, which was not confirmed by biopsy. The only significant clinical finding was a large abdominal aortic aneurysm. The 7 cm diameter and infrarenal origin of the aneurysm were confirmed by ultrasound and CT scans. Pulmonary function tests demonstrated reversible obstructive airways disease and a chest radiograph revealed a few small dense nodular regions in the left apical zone which had the appearances of inactive tubercle. A mantoux test and sputum examination for acid-fast bacilli were negative. Other haematological and biochemical investigations were normal. The patient's steroids were stopped and she
underwent uneventful repair of an infrarenal aortic aneurysm with an albumin-impregnated knitted Dacron ® tube graft. At operation the aneurysm was noted to have a saccular appearance but there was no evidence of periaortic inflammation. Intravenous antibiotic prophylaxis with three doses of flucloxacillin, cefuroxime and metronidazole was commenced at induction of anaesthesia. Thrombus with a normal appearance was obtained from the aneurysm sac and sent for routine microbiological culture. On microscopy Aspergillus niger was detected throughout the thrombus specimen and the organism was subsequently isolated from serial cultures on Sabouraud's agar. Treatment with intravenous amphotericin, building up within 5 days to 1 mg/kg body weight/day, was started at 48 h postoperatively. This was continued for 1 month at which time antifungal maintenance therapy was converted to oral itraconazote (an enterally absorbed triazole agent with less nephrotoxicity than amphotericin), 200 mg daily. Postoperatively the patient made an uneventful recovery and was discharged at 4 weeks. Prior to discharge an echocardiogram was obtained to exclude endocarditis as a source for mycotic emboli. Graft surveillance has since been carried out by serial CT scans and repeated Aspergillus complement fixation tests. An 111Indium-labelled leucocyte scan at 1 month revealed no evidence of increased uptake in the region of the graft, and there has been no change in the left apical opacities on chest radiography. At 12 months the patient is well and remains on oral itraconazole, with normal hepatic and renal function. CT scans reveal no evidence of graft infection. Discussion Fungi of the genus Aspergillus are widely distributed
0950-821X/94/030369+03 $08.00/0© 1994W. B. SaundersCompanyLtd.
370
F . C . T . Smith et al.
organisms of low pathogenicity to healthy humans.
characteristic saccular nature of this aneurysm, in the
Aspergillus fumigatus is the most common species to absence of predisposing factors such as smoking, perinfect the human, 1-5 although a case of aortic pseudoaneurysm infection by Aspergillus terreus has been reported. 6 To our knowledge no previous cases of aortic aneurysm infection by Aspergillus niger have been recorded and in routine microbiological examination of thrombus from over 500 aortic aneurysm repairs carried out by this department, no other case of Aspergillus has been detected. Aspergillus is a common contaminant, but that was unlikely in this case since repeated examination of thrombus from the aneurysm consistently revealed the hyphae and terminal conidiophores of A. niger throughout the specimen (Fig. 1).
Fig. 1. Aspergillusnigergrown from aneurysm thrombus. Hyphae (h) and terminal conidiophores (c) are indicated. Most cases of systemic Aspergitlus infection occur in patients with abnormal immune function, and immunosuppressive therapy is the most common predisposing factor in adults. It is likely that this patient developed a fungal mycotic aneurysm following prolonged treatment with steroids. The left apical lung lesion was probably the primary focus. Two similar cases have been reported in a renal transplant patient taking prednisolone, 1 who died following rupture of her aneurysm, and a patient treated with inhaled steroids. 4 Aortic aneurysm development as a direct consequence of Aspergillus infection is extremely rare although may occur secondary to embolic endocarditis, 2'5 and has followed coronary artery bypass surgery. 7 Whether, in this case, the organism infected thrombus in a pre-existing aneurysm, or was implicated in the primary development of the aneurysm remains unanswered. Direct invasion of the aortic wall by Aspergillus has been described, ~ and the Eur J VascSurg Vol 8, May 1994
ipheral vascular disease or hypertension, suggests the latter course. 1'3 Secondary Aspergillus infections of aortic grafts have been reported in several instances. 4'6'8 In these cases it is likely that the graft or aneurysm bed was infected by airborne spores at the time of operation. Manifestations of such infection have included late dehiscence of graft anastomoses with pseudoaneurysm formation and contiguous vertebral osteomyelitis. 4"6'8 Difficulty in diagnosis is due to non-specific systemic manifestations such as pyrexia, malaise and polymorphonuclear leucocytosis, compounded by the fact that Aspergillus is rarely cultured from blood. 3 Microscopy of infected tissue remains the mainstay of diagnosis. Where graft infection is established, the prognosis is poor 6 and successful management depends on early graft excision with debridement of the infected bed, extra-anatomic bypass and prolonged antifungal therapy.4' s H o w long should antifungal maintenance therapy be continued? Lack of specific serological tests for A. niger means that this question must be determined on an individual basis for each patient. Risk of infection recurrence has to be balanced against toxicity of treatment. In view of the reported disastrous consequences of graft infection, 4'6'8 treatment of our patient with itraconazole has been continued as long as hepatic and renal function tests have remained normal. Specific immunological tests for components of the organism wall are under development and may help resolve this question. The merits of routine microbial culture of aneurysm contents remain controversial. Several large series have documented positive cultures in 10-27% of patients undergoing aneurysm repair. 9-13 However, a five to ten-fold increase in late graft infections in patients with positive cultures, reported by some authors, 9"1° has not been confirmed in other studies. 11-13 Staphylococci, Streptococci and gram negative enteric bacteria are prevalent organisms in positive cultures but fungal growth was not reported in any of these studies. 9-13 Development of graft infection is a multifactorial process dependent on host immune status, organism virulence, type of prosthesis and use of antibiotics.lO, 12 On the basis of this case it is suggested that when a patient has potentially depressed immune function, culture and microscopy of aneurysm thrombus should be undertaken routinely. Appropriate therapy according to culture and sensitivity data, together with scrupulous long-term graft surveillance, may help avert the potentially cata-
Aspergillus niger Infection of Abdominal Aortic Aneurysm
strophic consequences of late prosthetic graft infection. References 1 MYEROWITZRL, FRIEDMANR, GROSSMANWL. Mycotic "mycotic aneurysm" of the aorta due to Aspergillusfumigatus. Am J Clin Path 1971; 55: 241-246. 2 DOSHI R. Aspergillusfumigatus endocarditis of an aortic homograft with aneurysm of the ascending aorta. J Pathol 1971; 103: 263-265. 3 Rose HD, STUARTJL. Mycotic aneurysm of the thoracic aorta caused by Aspergillusfumigatus. Chest 1976; 70: 81-84. 4 BRANDT SJ, THOMPSON RL, WENZEL RP. Mycotic pseudoaneurysm of an aortic bypass graft and contiguous vertebral osteomyelitis due to Aspergillus fumigatus. Am J Med 1985; 79: 259262. 5 CORRIGANC, HORNER SM. Aspergillus endocarditis in association with a false aortic aneurysm. Clin Cardiol 1988; 11: 430-432. 6 GLOTZBACHRE. Aspergillus terreus infection of pseudoaneurysm of aortofemoral vascular graft with contiguous vertebral osteomyelitis. Am J Clin Path 1982; 77: 224-227.
371
7 GRAY R, KAPLAN L, MATLOTTJ, UMAN S, SHACHTMANJ. Aortic pseudoaneurysm with Aspergillus aortitis. Chest 1986; 89: 306308. 8 ANDERSON J, KRON IL. Treatment of Aspergillus infection of the proximal aortic prosthetic graft with associated vertebral osteomyelitis. J Vasc Surg 1984; 1: 579-581. 9 ERNST CB, CAMPBELL HC, DAUGHERTY ME, SACHATELLO CR, GRIFTEN WO. Incidence and significance of intra-operative bacterial cultures during abdominal aneurysmectomy. Ann Surg 1977; 185: 626-633. 10 MACBETHGA, RUBIN JR, MCINTYRE KE, GOLDSTONEJ, MALONE JM. The relevance of arterial wall microbiology to the treatment of prosthetic graft infections: graft infection vs. arterial infection. J Vasc Surg 1984; 1: 750-756. 11 McAULEY CE, STEED DL, WEBSTER MW. Bacterial presence in aortic thrombus at elective aneurysm resection: Is it clinically significant? Am J Surg 1984; 147: 322-324. 12 SCHWARTZJA, POWELLTW, BURNHAMSJ, JOHNSON G. Culture of abdominal aortic aneurysm contents. Arch Surg 1987; 122: 777780. 13 STONEBRIDGE PA, MUTIRANGURAP, CLASON AE, RUCKLEYCV, JENKINSA McL. Bacteriology of aortic sac contents. J R Coll Surg Edinb 1990; 35: 42-43.
Eur J Vasc Surg Vol 8, May 1994
CASE REPORT A Hazard of Immunosuppression" A pergillus Abdominal Aortic Aneurysm
niger Infection of
F. C. T. Smith 1, E. Rees 2, T. S. J. Elliott 2 and C. P. Shearman I
University Departments of 1Surgery and 2Clinical Microbiology, Queen Elizabeth Hospital, Edgbaston, Birmingham, U.K.
Introduction We report the case of a female patient taking oral steroids who was found to have a true mycotic abdominal aortic aneurysm infected with Aspergillus niger. This illustrates a further hazard of steroid therapy and underlines the importance of establishing a diagnosis prior to their long term use. Aetiology and management of the case are discussed, and the importance of routine culture and microscopy of aneurysm contents in potentially immunosuppressed patients is emphasised.
Case Report A 74-year-old female was referred by her GP for surgical assessment of an asymptomatic abdominal aortic aneurysm found on routine clinical examination. She had chronic obstructive airways disease which had been treated with inhaled salbutamol and terbutaline for 5 years. One year previously she had been commenced on 4mg prednisolone daily for a presumptive diagnosis of temporal arteritis, which was not confirmed by biopsy. The only significant clinical finding was a large abdominal aortic aneurysm. The 7 cm diameter and infrarenal origin of the aneurysm were confirmed by ultrasound and CT scans. Pulmonary function tests demonstrated reversible obstructive airways disease and a chest radiograph revealed a few small dense nodular regions in the left apical zone which had the appearances of inactive tubercle. A mantoux test and sputum examination for acid-fast bacilli were negative. Other haematological and biochemical investigations were normal. The patient's steroids were stopped and she
underwent uneventful repair of an infrarenal aortic aneurysm with an albumin-impregnated knitted Dacron ® tube graft. At operation the aneurysm was noted to have a saccular appearance but there was no evidence of periaortic inflammation. Intravenous antibiotic prophylaxis with three doses of flucloxacillin, cefuroxime and metronidazole was commenced at induction of anaesthesia. Thrombus with a normal appearance was obtained from the aneurysm sac and sent for routine microbiological culture. On microscopy Aspergillus niger was detected throughout the thrombus specimen and the organism was subsequently isolated from serial cultures on Sabouraud's agar. Treatment with intravenous amphotericin, building up within 5 days to 1 mg/kg body weight/day, was started at 48 h postoperatively. This was continued for 1 month at which time antifungal maintenance therapy was converted to oral itraconazote (an enterally absorbed triazole agent with less nephrotoxicity than amphotericin), 200 mg daily. Postoperatively the patient made an uneventful recovery and was discharged at 4 weeks. Prior to discharge an echocardiogram was obtained to exclude endocarditis as a source for mycotic emboli. Graft surveillance has since been carried out by serial CT scans and repeated Aspergillus complement fixation tests. An 111Indium-labelled leucocyte scan at 1 month revealed no evidence of increased uptake in the region of the graft, and there has been no change in the left apical opacities on chest radiography. At 12 months the patient is well and remains on oral itraconazole, with normal hepatic and renal function. CT scans reveal no evidence of graft infection. Discussion Fungi of the genus Aspergillus are widely distributed
0950-821X/94/030369+03 $08.00/0© 1994W. B. SaundersCompanyLtd.
370
F . C . T . Smith et al.
organisms of low pathogenicity to healthy humans.
characteristic saccular nature of this aneurysm, in the
Aspergillus fumigatus is the most common species to absence of predisposing factors such as smoking, perinfect the human, 1-5 although a case of aortic pseudoaneurysm infection by Aspergillus terreus has been reported. 6 To our knowledge no previous cases of aortic aneurysm infection by Aspergillus niger have been recorded and in routine microbiological examination of thrombus from over 500 aortic aneurysm repairs carried out by this department, no other case of Aspergillus has been detected. Aspergillus is a common contaminant, but that was unlikely in this case since repeated examination of thrombus from the aneurysm consistently revealed the hyphae and terminal conidiophores of A. niger throughout the specimen (Fig. 1).
Fig. 1. Aspergillusnigergrown from aneurysm thrombus. Hyphae (h) and terminal conidiophores (c) are indicated. Most cases of systemic Aspergitlus infection occur in patients with abnormal immune function, and immunosuppressive therapy is the most common predisposing factor in adults. It is likely that this patient developed a fungal mycotic aneurysm following prolonged treatment with steroids. The left apical lung lesion was probably the primary focus. Two similar cases have been reported in a renal transplant patient taking prednisolone, 1 who died following rupture of her aneurysm, and a patient treated with inhaled steroids. 4 Aortic aneurysm development as a direct consequence of Aspergillus infection is extremely rare although may occur secondary to embolic endocarditis, 2'5 and has followed coronary artery bypass surgery. 7 Whether, in this case, the organism infected thrombus in a pre-existing aneurysm, or was implicated in the primary development of the aneurysm remains unanswered. Direct invasion of the aortic wall by Aspergillus has been described, ~ and the Eur J VascSurg Vol 8, May 1994
ipheral vascular disease or hypertension, suggests the latter course. 1'3 Secondary Aspergillus infections of aortic grafts have been reported in several instances. 4'6'8 In these cases it is likely that the graft or aneurysm bed was infected by airborne spores at the time of operation. Manifestations of such infection have included late dehiscence of graft anastomoses with pseudoaneurysm formation and contiguous vertebral osteomyelitis. 4"6'8 Difficulty in diagnosis is due to non-specific systemic manifestations such as pyrexia, malaise and polymorphonuclear leucocytosis, compounded by the fact that Aspergillus is rarely cultured from blood. 3 Microscopy of infected tissue remains the mainstay of diagnosis. Where graft infection is established, the prognosis is poor 6 and successful management depends on early graft excision with debridement of the infected bed, extra-anatomic bypass and prolonged antifungal therapy.4' s H o w long should antifungal maintenance therapy be continued? Lack of specific serological tests for A. niger means that this question must be determined on an individual basis for each patient. Risk of infection recurrence has to be balanced against toxicity of treatment. In view of the reported disastrous consequences of graft infection, 4'6'8 treatment of our patient with itraconazole has been continued as long as hepatic and renal function tests have remained normal. Specific immunological tests for components of the organism wall are under development and may help resolve this question. The merits of routine microbial culture of aneurysm contents remain controversial. Several large series have documented positive cultures in 10-27% of patients undergoing aneurysm repair. 9-13 However, a five to ten-fold increase in late graft infections in patients with positive cultures, reported by some authors, 9"1° has not been confirmed in other studies. 11-13 Staphylococci, Streptococci and gram negative enteric bacteria are prevalent organisms in positive cultures but fungal growth was not reported in any of these studies. 9-13 Development of graft infection is a multifactorial process dependent on host immune status, organism virulence, type of prosthesis and use of antibiotics.lO, 12 On the basis of this case it is suggested that when a patient has potentially depressed immune function, culture and microscopy of aneurysm thrombus should be undertaken routinely. Appropriate therapy according to culture and sensitivity data, together with scrupulous long-term graft surveillance, may help avert the potentially cata-
Aspergillus niger Infection of Abdominal Aortic Aneurysm
strophic consequences of late prosthetic graft infection. References 1 MYEROWITZRL, FRIEDMANR, GROSSMANWL. Mycotic "mycotic aneurysm" of the aorta due to Aspergillusfumigatus. Am J Clin Path 1971; 55: 241-246. 2 DOSHI R. Aspergillusfumigatus endocarditis of an aortic homograft with aneurysm of the ascending aorta. J Pathol 1971; 103: 263-265. 3 Rose HD, STUARTJL. Mycotic aneurysm of the thoracic aorta caused by Aspergillusfumigatus. Chest 1976; 70: 81-84. 4 BRANDT SJ, THOMPSON RL, WENZEL RP. Mycotic pseudoaneurysm of an aortic bypass graft and contiguous vertebral osteomyelitis due to Aspergillus fumigatus. Am J Med 1985; 79: 259262. 5 CORRIGANC, HORNER SM. Aspergillus endocarditis in association with a false aortic aneurysm. Clin Cardiol 1988; 11: 430-432. 6 GLOTZBACHRE. Aspergillus terreus infection of pseudoaneurysm of aortofemoral vascular graft with contiguous vertebral osteomyelitis. Am J Clin Path 1982; 77: 224-227.
371
7 GRAY R, KAPLAN L, MATLOTTJ, UMAN S, SHACHTMANJ. Aortic pseudoaneurysm with Aspergillus aortitis. Chest 1986; 89: 306308. 8 ANDERSON J, KRON IL. Treatment of Aspergillus infection of the proximal aortic prosthetic graft with associated vertebral osteomyelitis. J Vasc Surg 1984; 1: 579-581. 9 ERNST CB, CAMPBELL HC, DAUGHERTY ME, SACHATELLO CR, GRIFTEN WO. Incidence and significance of intra-operative bacterial cultures during abdominal aneurysmectomy. Ann Surg 1977; 185: 626-633. 10 MACBETHGA, RUBIN JR, MCINTYRE KE, GOLDSTONEJ, MALONE JM. The relevance of arterial wall microbiology to the treatment of prosthetic graft infections: graft infection vs. arterial infection. J Vasc Surg 1984; 1: 750-756. 11 McAULEY CE, STEED DL, WEBSTER MW. Bacterial presence in aortic thrombus at elective aneurysm resection: Is it clinically significant? Am J Surg 1984; 147: 322-324. 12 SCHWARTZJA, POWELLTW, BURNHAMSJ, JOHNSON G. Culture of abdominal aortic aneurysm contents. Arch Surg 1987; 122: 777780. 13 STONEBRIDGE PA, MUTIRANGURAP, CLASON AE, RUCKLEYCV, JENKINSA McL. Bacteriology of aortic sac contents. J R Coll Surg Edinb 1990; 35: 42-43.
Eur J Vasc Surg Vol 8, May 1994