4
Listeria monocytogenes as a rare cause of mycotic aortic aneurysm Ahmet Bal, MD, a Frank Schönleben, MD, a Abbas Agaimy, MD, b André Gessner, MD, PhD, c and Werner Lang, MD, a Erlangen, Germany Mycotic aneurysms represent a diagnostic and therapeutic challenge still lacking general recommendations for optimal therapy. So far, Listeria monocytogenes (L. monocytogenes) is very rarely reported to be the causative organism of mycotic aortic aneurysms. We report 2 cases of mycotic abdominal aortic aneurysms due to L. monocytogenes infection being treated by radical debridement, open in situ reconstruction with aorto-bi-iliac Dacron grafts, and long-term antibiotic therapy. Both patients recovered well from surgery. Interestingly, the long-time follow-up for the first patient 9 years after surgery was entirely uneventful. Open debridement in an in situ reconstruction with Dacron grafts followed by antibiotic therapy seems to be a suitable therapeutic regime for mycotic aneurysms due to L. monocytogenes. ( J Vasc Surg 2010;52:456-9.) Mycotic aneurysms of the aorta are rare complica- tions of systemic or metastatic infection and carry a high morbidity and mortality. Typical micro-organisms asso- ciated with mycotic aneurysms are Salmonella, Strepto- cocci, and Staphylococcus aureus. The main principles of treatment are antibiotic therapy, debridement, and res- toration of the circulatory system. Closure of the aortic stump and reconstruction by extra-anatomic axillo- bifemoral bypass is a conventional option, however, replacement by in situ repair with prosthetic or venous grafts and human homograft has been successful. A newer possible treatment option represents the aortic endograft, which, however, might be associated with a higher rate of necessary reintervention, since the infected aortic sac and surrounding tissue remain in situ. 1 There- fore, aortic endografts should be considered exclusively for emergency repair as a “bridging procedure.” Listeria monocytogenes (L. monocytogenes) is a bacterial pathogen well adapted to both, life in the soil and life in the cytosol of eukaryotic host cells. 2 This gram-positive sapro- phytic bacterium is ubiquitous and emerged in the latter 20th century as a food-borne pathogen. 3 After ingestion by a susceptible human, the bacterium is capable of the tran- sition to a physiological state that promotes bacterial sur- vival and replication in host cells. 4 In healthy individuals, L. monocytogenes is restricted to a self-limiting gastroen- teritis. However, in immunocompromised individuals and pregnant women, the bacterium may cause systemic infec- tions leading to encephalitis, meningitis and, in the case of pregnancy, to fetal infections, which can lead to abortion, stillbirth, or neonatal infections. 5 L. monocytogenes is rarely reported to be the causative organism of infected abdominal aortic aneurysms (AAAs). Accordingly, little is known about the pathogenesis and natural history of L. monocytogenes-induced mycotic aneu- rysms. We herein report 2 cases of mycotic AAAs due to infection with L. monocytogenes. Both were successfully treated by open in situ repair with implantation of aorto- bi-iliac Dacron grafts and additional antibiotic therapy. Of interest, we demonstrate the uneventful 9-year follow-up after surgical treatment for one of our patients. PATIENTS AND METHODS A 68-year-old man was referred to our hospital 9 years ago with acute pain in the left lower abdominal quadrant. At the time of admission, the patient was hypotensive and could be stabilized by volume substitution. Laboratory results showed signs of inflammation with C-reactive pro- tein (CRP) 179 mg /L (normal 12) and a white blood cell count of 24.8 10 9 /L (normal 3.5-11 10 9 /L). The hemoglobin was 8.2 g/dL (normal 12-16 g/dL) and the hematocrit value was 25% (normal 37% to 47%). Because of his medical history with diverticulosis and rectal cancer, the patient underwent a computed tomography (CT) imaging of the abdomen. This study revealed aortic rupture with retroperitoneal hematoma (Fig 1). Two years earlier, a CT scan revealed the presence of an ectatic aorta. The aneurysm was excised immediately and replaced by an aorto-bi-iliac Dacron graft (Albograft, Edwards Lifescience, Irvine, Calif). Since the aortic wall looked suspicious intraopera- tively, full thickness specimens were sent for culture and histopathological evaluation. An antibiotic therapy was started with piperacillin and tazobactam for the following 6 postoperative weeks. A 79-year-old man was referred to our hospital with fever and acute pain in the left lower abdominal quadrant. His recent medical history was remarkable for coronary heart disease, post-aortocoronary vein bypass, and perma- From the Department of Vascular Surgery, a Institute of Pathology, b Micro- biology Institute, Clinical Microbiology, Immunology and Hygiene, c University of Erlangen-Nuremberg. Competition of interest: none. Reprint requests: Frank Schönleben, MD, Department of Vascular Surgery, Krankenhausstraße 12, D-91052 Erlangen (e-mail: frank.schoenleben@ uk-erlangen.de). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a competition of interest. 0741-5214/$36.00 Copyright © 2010 by the Society for Vascular Surgery. doi:10.1016/j.jvs.2010.03.033 456

Listeria monocytogenes as a rare cause of mycotic aortic aneurysm

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Listeria monocytogenes as a rare cause of mycoticaortic aneurysmAhmet Bal, MD,a Frank Schönleben, MD,a Abbas Agaimy, MD,b André Gessner, MD, PhD,c andWerner Lang, MD,a Erlangen, Germany

Mycotic aneurysms represent a diagnostic and therapeutic challenge still lacking general recommendations for optimaltherapy. So far, Listeria monocytogenes (L. monocytogenes) is very rarely reported to be the causative organism of mycoticaortic aneurysms. We report 2 cases of mycotic abdominal aortic aneurysms due to L. monocytogenes infection beingtreated by radical debridement, open in situ reconstruction with aorto-bi-iliac Dacron grafts, and long-term antibiotictherapy. Both patients recovered well from surgery. Interestingly, the long-time follow-up for the first patient 9 yearsafter surgery was entirely uneventful. Open debridement in an in situ reconstruction with Dacron grafts followed byantibiotic therapy seems to be a suitable therapeutic regime for mycotic aneurysms due to L. monocytogenes. ( J Vasc Surg

2010;52:456-9.)

Mycotic aneurysms of the aorta are rare complica-tions of systemic or metastatic infection and carry a highmorbidity and mortality. Typical micro-organisms asso-ciated with mycotic aneurysms are Salmonella, Strepto-cocci, and Staphylococcus aureus. The main principles oftreatment are antibiotic therapy, debridement, and res-toration of the circulatory system. Closure of the aorticstump and reconstruction by extra-anatomic axillo-bifemoral bypass is a conventional option, however,replacement by in situ repair with prosthetic or venousgrafts and human homograft has been successful. Anewer possible treatment option represents the aorticendograft, which, however, might be associated with ahigher rate of necessary reintervention, since the infectedaortic sac and surrounding tissue remain in situ.1 There-fore, aortic endografts should be considered exclusivelyfor emergency repair as a “bridging procedure.”

Listeria monocytogenes (L. monocytogenes) is a bacterialpathogen well adapted to both, life in the soil and life in thecytosol of eukaryotic host cells.2 This gram-positive sapro-phytic bacterium is ubiquitous and emerged in the latter20th century as a food-borne pathogen.3 After ingestion bya susceptible human, the bacterium is capable of the tran-sition to a physiological state that promotes bacterial sur-vival and replication in host cells.4 In healthy individuals,L. monocytogenes is restricted to a self-limiting gastroen-teritis. However, in immunocompromised individuals andpregnant women, the bacterium may cause systemic infec-tions leading to encephalitis, meningitis and, in the case of

From the Department of Vascular Surgery,a Institute of Pathology,b Micro-biology Institute, Clinical Microbiology, Immunology and Hygiene,c

University of Erlangen-Nuremberg.Competition of interest: none.Reprint requests: Frank Schönleben, MD, Department of Vascular Surgery,

Krankenhausstraße 12, D-91052 Erlangen (e-mail: [email protected]).

The editors and reviewers of this article have no relevant financial relationshipsto disclose per the JVS policy that requires reviewers to decline review of anymanuscript for which they may have a competition of interest.

0741-5214/$36.00Copyright © 2010 by the Society for Vascular Surgery.

doi:10.1016/j.jvs.2010.03.033

456

pregnancy, to fetal infections, which can lead to abortion,stillbirth, or neonatal infections.5

L. monocytogenes is rarely reported to be the causativeorganism of infected abdominal aortic aneurysms (AAAs).Accordingly, little is known about the pathogenesis andnatural history of L. monocytogenes-induced mycotic aneu-rysms.

We herein report 2 cases of mycotic AAAs due toinfection with L. monocytogenes. Both were successfullytreated by open in situ repair with implantation of aorto-bi-iliac Dacron grafts and additional antibiotic therapy. Ofinterest, we demonstrate the uneventful 9-year follow-upafter surgical treatment for one of our patients.

PATIENTS AND METHODS

A 68-year-old man was referred to our hospital 9 yearsago with acute pain in the left lower abdominal quadrant.At the time of admission, the patient was hypotensive andcould be stabilized by volume substitution. Laboratoryresults showed signs of inflammation with C-reactive pro-tein (CRP) 179 mg /L (normal �12) and a white bloodcell count of 24.8 � 109/L (normal 3.5-11 � 109/L). Thehemoglobin was 8.2 g/dL (normal 12-16 g/dL) and thehematocrit value was 25% (normal 37% to 47%). Because ofhis medical history with diverticulosis and rectal cancer, thepatient underwent a computed tomography (CT) imagingof the abdomen. This study revealed aortic rupture withretroperitoneal hematoma (Fig 1). Two years earlier, a CTscan revealed the presence of an ectatic aorta. The aneurysmwas excised immediately and replaced by an aorto-bi-iliacDacron graft (Albograft, Edwards Lifescience, Irvine,Calif). Since the aortic wall looked suspicious intraopera-tively, full thickness specimens were sent for culture andhistopathological evaluation. An antibiotic therapy wasstarted with piperacillin and tazobactam for the following 6postoperative weeks.

A 79-year-old man was referred to our hospital withfever and acute pain in the left lower abdominal quadrant.His recent medical history was remarkable for coronary

heart disease, post-aortocoronary vein bypass, and perma-

JOURNAL OF VASCULAR SURGERYVolume 52, Number 2 Bal et al 457

nent atrial fibrillation under coumarin therapy. Laboratoryresults revealed an elevated CRP of 82 mg/L, a whiteblood count of 8.75 � 109/L, and a hematocrit value of39%. A CT of the abdomen showed an infrarenal AAA witha maximum diameter of 3.7 cm. CT-morphologically strik-ing was the aneurysm’s saccular shape and periaortic soft-tissue mass (Fig 2). Based on the radiological appearance, amycotic aneurysm was suspected and the decision for opensurgical repair by debridement and implantation of anaorto-bi-iliac Dacron graft (Gelsoft, Vascutek Ltd, Glas-gow, Scotland) was made. Subsequently, the graft wascovered by a trunculated omentum flap. Resected aorticwall and thrombus were sent in for further histopatho-logical and microbiological evaluation.

RESULTS

In the first patient, the gross specimen histopathologi-cally was composed of multiple irregular tan-yellow orgrayish tissue fragments that were gritty on sectioningowing to extensive calcifications. These showed hyalinefibrous tissue corresponding to aneurysmal wall with exces-sively calcified atherosclerotic plaques and fragments offresh thrombotic material, focally adherent to the vesselwall. Prominent aggregates of polymorphonuclear granu-locytes were evident within the inner wall and within thethrombotic material, occasionally showing phlegmonousextension through deep layers. The surrounding throm-botic material contained deeply violet-stained dense clumpsof bacterial micro-organisms (Fig 3, A-D). Microbiologicalevaluations of the resected material and the hematomayielded growth of L. monocytogenes (serotype 1/2a). Nineyears after surgery, we contacted the patient for follow-upand further analysis of his medical history. No remarkableinformation could be achieved about the disease-specific

Fig 1. Computed tomography (CT) scan of the first patientshowing the ruptured mycotic aneurysm and retroperitoneal he-matoma (see arrow).

history. A contrast enhanced control CT of the abdomen

showed a “lege artis” aortic reconstruction without anysigns of inflammation or reinfection. The patient has com-pletely recovered and is currently doing well.

In the second patient, histopathology showed a vari-able subacute inflammation within adventitial fibro-fattytissue with early granulation tissue formation and variableamounts of hemosiderin pigment as evidence of recurrenthemorrhages (Fig 2, E-F). Cultures of the aortic wall spec-imen yielded high numbers of L. monocytogenes (serotype4b) within 24 hours. According to the antibiogram, animmediate treatment with amoxicillin and clavulanate(875/125 mg) was started for 6 weeks. Postoperatively, theCRP was continuously declining and was back to normalafter 9 weeks. The patient has recovered from surgery andcurrently shows no clinical signs of infection 9 months aftersurgery.

DISCUSSION

Infected aortic aneurysms have been reported previouslyby several authors.6,7 The spectrum of causative micro-organisms consisted mainly of Staphylococcus aureus, Sal-monella species, and Streptococcus species.8 As a pathogen,L. monocytogenes infects a wide range of host species andhost cell types.9,10 The primary route of infection is acrossthe intestinal epithelium after ingestion of contaminatedfood. Infection models exist for both the intragastric andintravenous route as investigated in the past in severalanimal models.11 After transition into the bloodstream,most of the bacteria colonize in the liver and spleen. Unlesstheir replication is controlled by an effective host innateimmune response, L. monocytogenes may escape from im-mune clearance and continue to divide and replicate.12 Thesurvival of the host then depends on the development of aneffective adaptive immune response.

L. monocytogenes is able to replicate in the cytosol ofinfected host cells and to spread from cell to cell to avoidhumoral immune response.13

Aortic infections are believed to develop by pathogensoffending a vulnerable aortic wall. The focus of infectioncan develop in a normal caliber aorta or in a preexistinganeurysm. Arteriosclerosis is reported to be an additionalpredisposing factor for bacterial invasion, but it is notessential for infection, as shown previously in the literatureand by one of our cases.14 L. monocytogenes travel throughthe bloodstream and reach the vasa vasorum of the arterialwall or implant in damaged intima, ulcerated arterioscle-rotic plaques, or mural thrombus material.14 Alternatively,L. monocytogenes may invade the artery by contiguousspread from adjacent infectious processes.11

The optimal treatment strategy for patients with my-cotic aortic aneurysms still remains unknown. Here, thedecision for an open, anatomic repair was based on theknown rupture in our first patient, and on the episodes offever and imaging findings in the second patient to guar-antee adequate debridement of the infected aortic wall andsurrounding tissues. Endovascular repair appears to be anelegant alternative option, however, not in the presence of

rupture or fever.1 Furthermore, to date there is no general

JOURNAL OF VASCULAR SURGERYAugust 2010458 Bal et al

recommendation for the preferable type of graft, such asrifampicin- or silver-coated prosthesis, cryopreserved allo-grafts, or just plain Dacron grafts as used in our cases foranatomic reconstruction, since reported favorable resultsare mainly based on sporadic cases and not on evidencefrom controlled trials.15 With respect to the published dataand considering our 2 cases, a reasonable therapy for Listeria-

Fig 2. A and B, Computed tomography (CT) scan ofsurrounding inflammatory soft tissue mass (see arrows).

Fig 3. Histopathological findings (H&E stain) of infectA, Extensive atherosclerosis with calcifications (note thaggregates at higher magnification bordering calcified pclefts (lower midfield) and fibrin clots with dense bactebacterial organisms (seen as violet clumps). E, Overview otissue. F, Higher magnification of E.

induced aortic aneurysms seems to be surgical repair and

suitable antibiotic therapy. The optimal duration of antibi-otic therapy has not been evaluated in larger clinical studiesbut therapy for at least 6 weeks is recommended.8 How-ever, if there would have been strong macroscopic evidencefor the presence of bacterial colonization intraoperatively inboth cases, the operative strategy would have been changedto rifampicin- or silver-coated grafts, or even homograft, if

cond patient showing typical saccular morphology and

rtic aneurysms from patient 1 (A-D) and patient 2 (E-F).otic material in upper right field). B, Dense neutrophils. C, Inflamed mural thrombus containing cholesterolgregates (upper midfield). D, Higher magnification of2 showing inflammation within fibroadipose adventitial

the se

ed aoromblaque

rial agf case

available. Our first case represents, to our knowledge, the

JOURNAL OF VASCULAR SURGERYVolume 52, Number 2 Bal et al 459

longest follow-up after surgical repair and oral antibioticadministration for aortic aneurysm infected with L. mono-cytogenes. The aorto-bi-iliac graft still functions well anddoes not show any signs of inflammation on recent CTimaging.

In summary, open surgical repair and antibiotic therapyseems to be a suitable approach to L. monocytogenes-inducedmycotic aneurysms. Saccular and lobulated shaped aneu-rysms, adjacent soft-tissue mass, stranding, and/or fluid inan unusual location are imaging findings that are highlysuspicious of a mycotic aneurysm. Microbiological culturesfrom blood and, even more important, native aortic walltissue are essential to identify and confirm the causativemicro-organism, perform reliable antibiotic resistance test-ing, and start differentiated antibiotic therapy. A high sus-picion index and careful interpretation of image findingsare critical for early diagnosis and immediate appropriatetreatment of these aneurysms with a good chance for anuncomplicated long-term outcome.

REFERENCES

1. Kan CD, Lee HL, Yang YJ. Outcome after endovascular stent grafttreatment for mycotic aortic aneurysm: a systematic review. J Vasc Surg2007;46:906-12.

2. Gray ML, Killinger AH. Listeria monocytogenes and listeric infections.Bacteriol Rev 1966;30:309-82.

3. Fleming DW, Cochi SL, MacDonald KL, Brondum J, Hayes PS,Plikaytis BD, et al. Pasteurized milk as a vehicle of infection in an

outbreak of listeriosis. N Engl J Med 1985;312:404-7.

4. Freitag NE. From hot dogs to host cells: how the bacterial pathogenListeria monocytogenes regulates virulence gene expression. FutureMicrobiol 2006;1:89-101.

5. Drevets DA, Bronze MS. Listeria monocytogenes: epidemiology, hu-man disease, and mechanisms of brain invasion. FEMS Immunol MedMicrobiol 2008;53:151-65.

6. Patel S, Johnston KW. Classification and management of mycoticaneurysms. Surg Gynecol Obstet 1977;144:691-4.

7. Nakata Y, Shionoya S, Kamiya K. Pathogenesis of mycotic aneurysm.Angiology 1968;19:593-601.

8. Goddeeris K, Daenens K, Moulin-Romsee G, Blockmans D. Chronic-contained rupture of an infected aneurysm of the abdominal aorta dueto Listeria monocytogenes. Neth J Med 2006;64:85-7.

9. Lecuit M. Human listeriosis and animal models. Microbes Infect 2007;9:1216-25.

10. Seveau S, Pizarro-Cerda J, Cossart P. Molecular mechanisms exploitedby Listeria monocytogenes during host cell invasion. Microbes Infect2007;9:1167-75.

11. Freitag NE, Port GC, Miner MD. Listeria monocytogenes - fromsaprophyte to intracellular pathogen. Nat Rev Microbiol 2009;7:623-8.

12. Zenewicz LA, Shen H. Innate and adaptive immune responses toListeria monocytogenes: a short overview. Microbes Infect 2007;9:1208-15.

13. Pamer EG. Immune responses to Listeria monocytogenes. Nat RevImmunol 2004;4:812-23.

14. Macedo TA, Stanson AW, Oderich GS, Johnson CM, Panneton JM,Tie ML. Infected aortic aneurysms: imaging findings. Radiology 2004;231:250-7.

15. Zhou W, Lin PH, Bush RL, Terramani TT, Matsuura JH, Cox M, et al.In situ reconstruction with cryopreserved arterial allografts for manage-ment of mycotic aneurysms or aortic prosthetic graft infections: amulti-institutional experience. Tex Heart Inst J 2006;33:14-8.

Submitted Jan 12, 2010; accepted Mar 20, 2010.