Graft infection after a Bentall procedure: A case series and systematic review of the literature

    Graft Infection after A Bentall Procedure: A Case Series And Systematic Review Of The Literature I Machelart, C Greib, G Wirth, F Camou, N Issa, J.F Viallard, JL Pellegrin, E Lazaro PII: DOI: Reference:

S0732-8893(17)30078-0 doi: 10.1016/j.diagmicrobio.2017.03.002 DMB 14314

To appear in:

Diagnostic Microbiology and Infectious Disease

Received date: Revised date: Accepted date:

27 November 2016 24 February 2017 3 March 2017

Please cite this article as: Machelart I, Greib C, Wirth G, Camou F, Issa N, Viallard JF, Pellegrin JL, Lazaro E, Graft Infection after A Bentall Procedure: A Case Series And Systematic Review Of The Literature, Diagnostic Microbiology and Infectious Disease (2017), doi: 10.1016/j.diagmicrobio.2017.03.002

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ACCEPTED MANUSCRIPT GRAFT INFECTION AFTER A BENTALL PROCEDURE: A CASE SERIES AND SYSTEMATIC REVIEW OF THE LITERATURE Machelart I1, Greib C1, Wirth G2, Camou F3, Issa N3, Viallard J.F1, Pellegrin JL1, Lazaro E1. Department of Internal Medicine and Infectious Diseases, Haut-Lévêque Hospital, Pessac, France

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Department of Infectious Diseases, Pellegrin Hospital, Bordeaux, France

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Medical Intensive Care Unit, Saint André Hospital, Bordeaux, France

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ACKNOWLEDGEMENTS We thank JetPub Scientific Editing Services for English language editing and helpful comments.

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ACCEPTED MANUSCRIPT ABSTRACT Introduction: The Bentall procedure is a cardiac surgery involving graft replacement of the aortic valve, aortic root and ascending aorta. Graft infection after Bentall’s procedure (BGI) is infrequent but

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severe, and often difficult to diagnose and treat.

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Patients and Methods: A retrospective cohort study was performed using the Bordeaux endocarditis database of adult patients admitted to the Bordeaux University Medical Hospital for BGI between 2008 and 2014. Published case reports were identified in the literature.

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Results: We identified 10 BGI patients in the database and 13 in the literature. The majority of infections were late-onset (20/23) and occurred as a result of gram positive cocci bacterial infection

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(16/22). Detailed diagnoses of the described BGI were determined using echocardiography, computed tomography (CT) and positron emission tomography/CT (PET/CT). Labeled-leukocyte scintigraphy was not reported in any case. Prolonged antibiotic therapy and surgery were found to be the treatment of choice for BGI, however it was not always possible to perform a surgical intervention. Clinical relapses occurred even with a negative PET/CT, while PET/CT consistenly positive for BGI occurred in the absence of clinical relapse. This suggests that the use of PET/CT for follow-up is questionable.

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Conclusion: Diagnosis of BGI is difficult, due to the combination of clinical, biological, and radiological observations obtained through transoesophageal echocardiography and CT. PET/CT is an

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alternative method to diagnosis BGI, but its impact on clinical management remains unclear. Current data suggests that if surgical replacement of the prosthesis is not possible, patients should be treated

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with prolonged antibiotic therapy.

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ACCEPTED MANUSCRIPT INTRODUCTION A Bentall procedure is a cardiac surgery involving composite graft replacement of the aortic valve, aortic root and ascending aorta, and a re-implantation of the coronary arteries into the graft (1). This

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surgery is indicated for a large spectrum of pathological conditions involving aortic regurgitation,

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Marfan’s syndrome, aortic dissection, and aortic aneurysm. This procedure is complicated by infection in 1.4% of cases (2).

Data are lacking regarding the diagnostic strategy and treatment of graft infection after a Bentall

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procedure (BGI). In this article, we consider 23 cases including a case series of 10 patients managed in our institution and 13 published cases, to determine an improved process of diagnosis and treatment

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for BGI.

METHODS Patients

A retrospective study was performed using all adult patients admitted to the Bordeaux University

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Medical Hospital for BGI between 2008 and 2014 as recorded in the Bordeaux endocarditis database accredited by the French national data protection commission (CNIL number: 2009020).

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Epidemiological, and clinical characteristics, as well as outcomes, were recorded for each patient. Literature analysis

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Published case reports were identified in a Medline search of literature reported in the Englishlanguage from the years 1968 to 2016. The following keywords were used: vascular graft infection

Definitions

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(VGI), Bentall procedure, endocarditis.

BGI was defined by VGI and/or aortic endocarditis, according to specific criteria proposed by Fitzgerald et al. (3). VGI was diagnosed in a patient if at least two of the three following criteria were present: (i) clinical signs of infection (fever, chills, septic shock); (ii) positive bacterial culture or bacterial polymerase chain reaction (PCR) of intraoperative specimens or blood samples; (iii) biological signs of infection (C-reactive protein > 10 mg/L, white blood count > 10 G/L) or other radiological signs of infection diagnosed by computed tomography (CT), echocardiography or positron emission tomography/CT (PET/CT). A diagnosis of associated endocarditis was made according to the modified Duke criteria that include the confirmation of the presence of microorganisms and specific echocardiographic observations, as previously described (4). Each case of VGI was classified either as early-onset infection (occurring within 4 months after surgery) or lateonset infection (occurring more than 4 months after surgery). As four months is considered the gold standard for onset of VGI, and corresponds to the timeframe during which both VGI and IE are classified as early-onset, it was selected as the threshold between early and late infection. 3

ACCEPTED MANUSCRIPT RESULTS Characteristics of BGI cases Ten patients with BGI were identified over a seven-year period from our institutional database and

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included both early- (n=1) and late-onset (n=9) cases with a median follow-up time from diagnosis of

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30.5 months [interquartile range (IQR) 18-46 months]. The main clinical and biological characteristics are described in Table 1.

The median age at diagnosis of BGI was 74 years (IQR 69-76.5years) and 90% were male. The

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valvular prosthesis was a bioprosthesis in seven cases. Half of the patients had risk factors for infection: diabetes mellitus (n=2), neutropenia (n=1), immunodepression defined by steroid therapy >

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7.5 mg per day and/or immunosuppressive treatments (n=2). Most of the patients had numerous comorbidities: medical history of cardiovascular disease independent from the Bentall intervention (n=5), at least two risk factors for cardiovascular disease (n=3), and medical history of cancer (n=2). The mean values of white blood cell count and C-reactive protein were 8.9 3.3 G/L and 88.670.2 mg/L, respectively.

At admission, clinical signs suggesting an infectious process involving the prosthetic vascular graft

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were fever > 38°C (n=10) and general deterioration (n=4). Presentation of clinical complications were frequent: septic emboli (splenic (n=2), cerebral (n=1)), spondylodiscitis (n=2), abscess (n=2), left

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ventricular fistulae (n=2), rupture of a cerebral mycotic aneurysm (n=1), and transient ischemic attack (n=1). These complications were present at admission with the exception of one patient who presented

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spondylodiscitis and rupture of a cerebral mycotic aneurysm during follow-up. Relationship between radiological imaging and BGI diagnosis

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Of 10 patients, nine underwent both transthoracic echocardiography (TTE) and transoesophageal echocardiography (TEE). TTE was normal in all cases with the exception of two, in which a potential abscess was visualized. TEE was abnormal in seven cases, with isolated signs of aortic endocarditis in five cases. The specific details included vegetations (n=3), abscesses on the valvular prosthesis (n=2) and both signs of endocarditis and vascular prosthesis infection (n=2). Of the eight cases that used CT, only three showed radiological signs of infection. PET combined with CT (PET/CT) was performed in seven cases and showed signs for BGI in each patient. Presentation of endocarditis in these seven patients was the following: only endocarditis (n=2) or endocarditis and VGI (n=5). From the same seven cases, results of TEE or CT suggested BGI except for one patient. PET/CT showed an abnormal uptake on the valvular prosthesis and/or on the vascular prosthesis with a mean standardized uptake value (SUV) maximum of 4.5 (IQR 4-6.6). Labeled-leukocyte scintigraphy was not performed in any of the patients. Taken together, TTE, TEE, CT and/or PET/CT are able to diagnose BGI to varying degrees, since analysis of the scans showed positive signs of endocarditis (n=2), VGI (n=1), or both endocarditis and VGI (n=7) (Table 2).

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ACCEPTED MANUSCRIPT Analysis of microbiological data, treatment, and outcomes As summarized in Table 3, microbiological data was obtained for nine patients, and a total of 12 causative microorganisms were isolated from blood culture (n=7) or by PCR (n=2): Methicillinresistant Staphylococcus epidermidis (MRSE, n=2), Methicillin-sensitive Staphylococcus epidermidis

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(MSSE, n=2), Streptococcus agalactiae (n=1), Enterococcus faecalis (n=1), Streptococcus sanguinis

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(n=1), Candida parapsilosis (n=1), Achromobacter species (n=1), Serratia marcescens (n=1), Bartonella quintana (n=1) and Coxiella burnetii (n=1). Seven patients had concomitant bacteriemia, while one patient had a polymicrobial infection involving MRSE, Candida parapsilosis,

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Achromobacter species, and Serratia marcescens. In three cases, the bacterial port-of-entry was identified: the Streptococcus agalactiae infection was of dental origin; the polymicrobial infection

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occurred at the surgical site; and the Enterococcus faecalis infection was of digestive origin. All patients were treated with antibiotics, according to the causative organism and antibiotic sensitivity. The median duration of treatment was 7 months (IQR 5-13.5 months), including a median intravenous therapy duration of 2 weeks (IQR 0.7-7 weeks). Two patients underwent surgery two days and 28 days after BGI diagnosis to complete the Bentall procedure and valvular bioprosthesis

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replacement, and drainage of an abscess, respectively. Among the six patients who received complete antibiotic therapy, the mean duration was 10.5 months. Over the course of the entire follow-up period, two patients died. One death was a result of hemorrhagic stroke after six weeks of treatment while

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magnetic resonance angiography did not show evidence of mycotic aneurysm. The other death was a result of an uncontrolled systemic polymicrobial infection with septic emboli and mycotic aneurysms

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after 18 months of antibiotic treatment. Neither patient underwent surgical intervention. Contact with one patient who started antibiotic treatment was lost during follow-up. One patient has received

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antibiotic treatment for six months for Coxiella burnetii BGI, and continues to receive treatment. Of the six patients with a mean post-treatment follow up >2 years, remission of infection was observed in four patients. This occurred after a median duration of antibiotic treatment of 7 (5.4-8.6) months, during which time one patient underwent surgery. The patients that went into remission showed positive PET/CT at diagnosis, while two patients still showed positive PET/CT at the end of the treatment (mean 9.25 months). No patients relapsed with a mean follow-up of 32 months after antibiotic treatment. Relapse of BGI following antibiotic treatment occurred in two patients. In the first, at the end of a sixmonth antibiotic treatment for a MSSE-BGI, including three weeks of intravenous therapy, the blood culture and PET/CT analysis diagnosed spondylodiscitis with no evidence of BGI relapse. However, the relapse occurred one month after the antibiotic treatment was completed, and after 24 months of antibiotic treatment, the patient went into remission (post-treatment follow up: 12 months). The other patient who developed a Streptococcus sanguinis BGI, underwent surgery with abscess drainage, complete prosthesis replacement, and eight weeks of antibiotic therapy after surgery without control 5

ACCEPTED MANUSCRIPT TEE and CT (that led to diagnosis) at the end of treatment. The relapse occurred one month after discontinuing the antibiotic therapy related to a vegetation with a periprosthetic false-aneurysm. Remission was obtained after six weeks of antibiotics (post-treatment follow-up: 18 months).

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Review of published BGI infections

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To date, 13 cases of BGI have been published (5–9), and the results are summarized in Table 4. Microbial documentation was available in 12 cases, and revealed that the majority of infections were late-onset and due to gram-positive cocci bacteria (n=10). Radiologic findings were not described for

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nearly half of the patients. Interestingly, 12 patients benefited from surgical intervention, the majority of which were a prosthesis replacement. In one case, a staged graft-sparing surgical approach was performed. The range of duration of antibiotic therapy to individual cases included several weeks (9),

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several months (8), or eight months (7), The patient with a BGI that did not undergo further surgery was treated with antibiotics for three years (9). In the series reported by Coselli et al., heterogeneous antibiotic therapy was prescribed, with the duration of treatment ranging from several weeks to lifelong.

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DISCUSSION

Infectious complications after a Bentall procedure are rare (1.4%) (2) but severe, and not well-

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documented. Most published studies focus on VGI in general, but only a few studies report specific outcomes of the Bentall procedure (2), (10–13). VGI is a rare but severe complication in vascular

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surgery, and has a low prevalence (< 5%) (14). Contamination of the graft may spread through the blood or lymphatic system, or result from faulty sterile surgical technique (15). From a microbial

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perspective, there is a predominance of Staphylococcus aureus infections (35%), with a recent 20% increase in Methicillin-resistant Staphylococcus aureus infections (16) associated with VGI. In our study, Staphylococcus epidermidis (SE) (Methicillin-resistant in half of the cases) was the most frequent cause of infection.

The management of BGI is difficult due to the variability of diagnosis and treatment. A diagnosis of BGI utilizes a variety of tests to demonstrate the presence of an aortic prosthetic valve infective endocarditis (IE) with a VGI. TEE plays a key role in the assessment of IE, but is not always conclusive due to the numerous artifacts related to the presence of the prosthesis. Furthermore, since IE can be diagnosed by CT (15),(17) with a sensitivity and specificity rate close to 100% for acute infections, TEE is less valuable to assess the presence of aortic infection. In most of the published reports (Table 4), the diagnosis of BGI used a combination of TTE, TEE, CT and PET/CT. In our study, TEE performed in nine cases demonstrated signs of BGI (n=7), of which five cases showed signs of endocarditis, but not vascular infection, whereas CT contributed to the diagnosis of BGI in only three cases of the eight performed. 6

ACCEPTED MANUSCRIPT More recently, PET/CT has been indicated in order to diagnose prosthetic valve endocarditis in patients with difficult echocardiographic or CT diagnosis (small vegetations, prosthetic valves, or indwelling pacemakers) (18,19). Two recent studies showed that PET/CT increased sensitivity of the modified Duke criteria when results were combined with clinical, microbial, and echocardiographic

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parameters (20),(21). Several published case series have presented preliminary data on the role of PET

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and PET/CT in VGI (18,19) with a sensitivity range of 70 to 93%, and specificity range of 91 to 93% in VGI. Although the lack of specificity is a major limitation of the PET/CT scan, for each of our patients for which PET/CT scans were available (n=7), we were able to make a conclusive diagnosis.

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While a negative result virtually eliminates the diagnosis, a positive result should be interpreted with caution, and made in combination with clinical, microbial, and echocardiographic or CT parameters.

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As a result of this lack of specificity, a positive PET at the end of antibiotic treatment is due to a chronic aseptic inflammation in synthetic graft material, and is not a good predictor of relapse (22). Scintigraphy with tagged leukocytes has been described to be superior to CT to diagnose late VGI, and is also considered a functional imaging gold standard (23,24). Its sensitivity and specificity are close to 100% (25), but there are numerous limitations, such as a lack of postoperative sensitivity.

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Scintigraphy was not processed in our study. Similarly, none of the published cases were diagnosed through leukocyte-labeled scintigraphy. Only one study has compared PET/CT and labeled leukocyte scintigraphy in VGI, showing the same sensitivity (100%), but an improved specificity for

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scintigraphy (100% versus 92%, n=22) (26).

Although these data do not place PET/CT or leukocyte-labeled scintigraphy as the premiere tool to

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diagnose BGI, it suggests that these methods can be helpful for patients with a clinical suspicion of BGI, and inconclusive or negative results on initial echocardiography or CT.

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Regarding medical and surgical treatment, only two of the patients followed in our institution underwent surgery, unlike the published cases in which the majority underwent surgical intervention. This was most likely due to the fact that most of our patients had significant comorbidities (50% had an immunodepression or were diabetics). In VGI, prosthesis replacement is considered as the gold standard of treatment. Surgery is not indicated when it is not possible to replace the vascular prosthesis due to the advanced age or fragility of the patients since there is a high rate of re-infection and death in these populations (16),(27,28). There are no general surgical guidelines for the treatment of ascending aorta and aortic arch prosthetic graft infection (29). Traditionally, it is thought that removal and in situ replacement of the prosthetic material is mandatory. However, surgical morbidity and mortality are still a major concern with traditional replacement due to the invasive and complex procedure, the state of emergency, potential for field contamination, and the difficulties of exposure of the prosthesis (30). In addition to surgery, antibiotic therapy is a key treatment of BGI. Each therapy must be adapted to the type of bacteria, and should be conservative with respect to duration based on clinical and

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ACCEPTED MANUSCRIPT radiological evaluation. The majority of the published case-reports follow a long-term antibiotic therapy. In our database study, four patients did not finish the treatment due to death (n=2), loss on follow-up (n=1), or ongoing treatment (n=1). Among the six patients who received complete antibiotic therapy, the mean duration was 10.5 months. Without prosthesis replacement, each of these patients

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healed, with two healing after relapse. In this context, it is difficult to determine when antibiotic

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treatment should be discontinued and if PET/CT will benefit the outcome.

In our series, the PET/CT was negative in the majority of cases when antibiotic treatment was stopped.

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In two cases, PET/CT was positive at the end of the treatment and relapse did not occur. One patient who relapsed had a negative PET/CT at the end of treatment. These data suggest that although PET/CT can be useful in diagnosing BGI, it lacks sensitivity and specificity in follow up of BGI, and

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should therefore be interpreted in combination with clinical, biological and radiological parameters.

CONCLUSION

BGI is a rare but severe complication of the Bentall procedure. Treatment of BGI was previously

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based on surgical removal of the infected graft followed by prolonged antibiotic therapy. However, a large number of patients cannot have a prosthesis replacement because of surgical risks, and therefore conservative treatment would benefit those cases. In our series of 10 patients, 60% of patients were

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definitively healed, 20% healed following relapse, and 20% died. Clinical, microbial, and radiological arguments make the diagnosis of BGI difficult. If BGI diagnosis is negative by TEE and CT, PET/CT

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or leukocyte-labeled scintigraphy can play key roles in diagnosing this infection. However, whether PET/CT is beneficial during follow-up remains to be confirmed. Therefore, further research is

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warranted to determine improved diagnosis and treatment for BGI.

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ACCEPTED MANUSCRIPT Table 1 : Clinical characteristics of the BGI patients Definite endocar -ditis

79 59 57 74 72 74 68 80 77 75

F M M M M M M M M M

bioprothesis mechanical mechanical bioprothesis mechanical bioprothesis bioprothesis bioprothesis bioprothesis bioprothesis

yes yes yes yes yes no yes yes yes no

yes yes no yes yes yes yes yes yes yes

White blood cell count (G/L) 13.1 2.2 8.46 5.03 9.8 9.35 7.9 11.2 12.31 9.84

CRP (mg/L)

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Definite VGI

204 11 13 29 130 167 110 80 129 13

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Type of valvular prothesis

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Gender

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Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 Patient 9 Patient 10

Age

Time to infection

3 years 6 years 5 days 2 years 9 years 3 years 1 years 3 years 8 years 2 years

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F: Female; M: Male; G/L: Giga/Liter; CRP: C-reactive-protein; mg/mL: milligram/milliliter

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Followup (months)

48 30.5 18 1.5 46 Lost 39 68 22 4

ACCEPTED MANUSCRIPT Table 2 : Radiological data leading to BGI diagnosis CT Valvular and aortic root reorganization neg

PET/CT Valvular and vascular graft root uptake Valvular and vascular graft uptake NA

Diagnosis CT + PET/CT

Patient 2

neg

Valvular vegetation

Patient 3

neg

NA

Patient 4

neg

Valvular vegetation

Valvular and vascular graft root uptake Perivascular and perivalvular graft uptake NA

TEE + PET/CT

Patient 5

neg

Valvular abcess

Patient 6

neg

neg

Patient 7

neg

Valvular vegetation neg

Valvular and vascular graft uptake Valvular uptake

PET/CT

Patient 8

neg

neg

Patient 9

Abcess (suspiscion)

Patient 10

Abcess (suspiscion)

Valvular vegetation + 10mm hyperechoic image on vascular graft Vascular periprosthetic abcess Valvular leak Aortic annulus abcess

Periprosthetic abcess

NA

TEE + CT

NA

Valvular uptake

TEE + PET/CT

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TEE neg

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Patient 1

TTE neg

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Vascular periprosthetic collection neg

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NA

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neg

TEE + PET/CT CT

TEE + PET/CT TEE

TEE + PET/CT

Neg: negative; TTE: Transthoracic echocardiography; TEE: Transoesophageal Echocardiography; CT: Computed Tomography; PET/CT: Positron Emission Tomography/Computed tomography; NA: Not Applicable

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ACCEPTED MANUSCRIPT Table 3: Microbial characteristics, treatment, and outcome of patients Surgery

Lenght of IV ATB

no no no

7.5 months 7 weeks 6 weeks

Patient 4

MRSE Streptococcus agalactiae Candida parapsilosis Achromobacter species Serratia marcescens MRSE Bartonella quintana

Total duration of ATB 7.5 months 6.5 months 1.5 years

no

3 days

1.5 months

Patient 5

MSSE

no

5 days

6 months

Patient 6

MSSE

NA

NA

Patient 7 Patient 8 Patient 9

NA Enterococcus faecalis Streptococcus sanguinis

1 year 2 weeks 2 weeks

1 year 2.4 years 2 months

Patient 10

Coxiella burnetii

Bioprothesis replacement no no Bentall graft replacement no

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Presently ongoing

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Patient 1 Patient 2 Patient 3

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Microorganisms

Follow-up

Remission Remission Death related to BGI

Death not related to BGI Remission after relapse Lost to follow-up Remission Remission Remission after relapse Treatment ongoing

NA: not applicable; IV: intraveinous; ATB: antibiotherapy; MRSE: Methicillin-Resistant Staphylococcus Epidermidis; MSSE: Methicillin-Sensitive Staphylococcus Epidermidis; BGI: Bentall

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Graft Infection

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ACCEPTED MANUSCRIPT

Table 4: Summary of published findings for BGI patients

Case 1

Late

CT

Methicillin-resistant Staphylococcus epidermidis

Case 2

Late

CT

Methicillin-sensitive Staphylococcus aureus

Case 3

Late

PET/CT

Alpha streptococcus

BG replacement

ATB duration

Outcome

Yes

NA

Remission

Yes

NA

Remission

No

3 years

Remission

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Microbiology

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Diagnosis

Case 4

Late

TEE

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Takano et al. (5)

Time

Staphylococcus hominis

Yes

NA

Remission

Case 5

Late

NA

Staphylococcus epidermidis

Yes

« lifelong »

Remission

Case 6

Late

NA

Staphylococcus aureus

Yes

« lifelong »

Remission

Case 7

Late

NA

Streptococcus, Enterococcus

Yes

« lifelong »

Remission

Case 8

Early

NA

Stapylococcus coagulase negative

Yes

« lifelong »

Case 9

Late

NA

Gram-negative bacilli, Candida

Yes

« lifelong »

Case 10

Late

NA

Staphylococcus aureus

Yes

« lifelong »

Remission Died 5 months later due to myocardial infarction Death related to infection Death due to infection

Sharifkazemi (8) Hussein (7)

Case 11

Late

TEE

Brucella melitensis

Yes

Several months

Remission

Case 12

Early

TTE

Finegoldia magna

Yes

8 months

Remission

Tossios et al. (9)

Case 13

Late

TTE+CT

NA

No (conservative surgery)

Several weeks

Remission

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Coselli et al. (6)

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Enterococcus faecalis

BG: Bentall Graft; CT: Computed Tomography: TTE: Trans-Thoracic echocardiography; TEE: Trans Oesophageal Echocardiography; PET/CT: Positron Emission Tomography/Computed tomography; NA: Not Applicable; ATB: antibiotic therapy

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ACCEPTED MANUSCRIPT COMPLIANCE WITH ETHICAL STANDARDS: Informed consent was obtained from all individual participants included in the database, accredited by the French national data protection commission (CNIL number 2009020).

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The protocol was not submitted to the Ethics Committees as the collected data were derived from

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routine clinical practice, no additional testing was requested of the patients, and analysis was

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performed as aggregate data.

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ACCEPTED MANUSCRIPT REFERENCES 1. Bentall H, De Bono A. A technique for complete replacement of the ascending aorta. Thorax. juill 1968;23(4):338‑9.

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2. Joo H-C, Chang B-C, Youn Y-N, Yoo K-J, Lee S. Clinical experience with the Bentall procedure: 28 years. Yonsei Med J. sept 2012;53(5):915‑23. 3. FitzGerald SF, Kelly C, Humphreys H. Diagnosis and treatment of prosthetic aortic graft infections: confusion and inconsistency in the absence of evidence or consensus. J Antimicrob Chemother. déc 2005;56(6):996‑9.

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10. Schachner T, Vertacnik K, Nagiller J, Laufer G, Bonatti J. Factors associated with mortality and long time survival in patients undergoing modified Bentall operations. J Cardiovasc Surg (Torino). oct 2005;46(5):449‑55. 11. Prifti E, Bonacchi M, Frati G, Proietti P, Giunti G, Babatasi G, et al. Early and long-term outcome in patients undergoing aortic root replacement with composite graft according to the Bentall’s technique. Eur J Cardio-Thorac Surg Off J Eur Assoc Cardio-Thorac Surg. janv 2002;21(1):15‑21. 12. Varrica A, Satriano A, de Vincentiis C, Biondi A, Trimarchi S, Ranucci M, et al. Bentall operation in 375 patients: long-term results and predictors of death. J Heart Valve Dis. janv 2014;23(1):127‑34. 13. Nishida T, Sonoda H, Oishi Y, Ushijima T, Tanoue Y, Nakashima A, et al. More than 20-year experience of Bentall operation with mechanical prostheses for chronic aortic root aneurysm. Gen Thorac Cardiovasc Surg. févr 2015;63(2):78‑85. 14. Cavalcanti Filho JLG, de Souza Leão Lima R, de Souza Machado Neto L, Kayat Bittencourt L, Domingues RC, da Fonseca LMB. PET/CT and vascular disease: current concepts. Eur J Radiol. oct 2011;80(1):60‑7.

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ACCEPTED MANUSCRIPT 15. Keidar Z, Nitecki S. FDG-PET for the detection of infected vascular grafts. Q J Nucl Med Mol Imaging Off Publ Ital Assoc Nucl Med AIMN Int Assoc Radiopharmacol IAR Sect Soc Radiopharm Chem Biol. févr 2009;53(1):35‑40.

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19. Spacek M, Belohlavek O, Votrubova J, Sebesta P, Stadler P. Diagnostics of « non-acute » vascular prosthesis infection using 18F-FDG PET/CT: our experience with 96 prostheses. Eur J Nucl Med Mol Imaging. mai 2009;36(5):850‑8. 20. Graziosi M, Nanni C, Lorenzini M, Diemberger I, Bonfiglioli R, Pasquale F, et al. Role of 18FFDG PET/CT in the diagnosis of infective endocarditis in patients with an implanted cardiac device: a prospective study. Eur J Nucl Med Mol Imaging. août 2014;41(8):1617‑23.

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21. Saby L, Laas O, Habib G, Cammilleri S, Mancini J, Tessonnier L, et al. Positron emission tomography/computed tomography for diagnosis of prosthetic valve endocarditis: increased valvular 18F-fluorodeoxyglucose uptake as a novel major criterion. J Am Coll Cardiol. 11 juin 2013;61(23):2374‑82.

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22. Wassélius J, Malmstedt J, Kalin B, Larsson S, Sundin A, Hedin U, et al. High 18F-FDG Uptake in synthetic aortic vascular grafts on PET/CT in symptomatic and asymptomatic patients. J Nucl Med Off Publ Soc Nucl Med. oct 2008;49(10):1601‑5.

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23. Prats E, Banzo J, Abós MD, Garcia-Lopez F, Escalera T, Garcia-Miralles M, et al. Diagnosis of prosthetic vascular graft infection by technetium-99m-HMPAO-labeled leukocytes. J Nucl Med Off Publ Soc Nucl Med. août 1994;35(8):1303‑7.

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24. Liberatore M, Iurilli AP, Ponzo F, Prosperi D, Santini C, Baiocchi P, et al. Clinical usefulness of technetium-99m-HMPAO-labeled leukocyte scan in prosthetic vascular graft infection. J Nucl Med Off Publ Soc Nucl Med. mai 1998;39(5):875‑9. 25. Delgado M, Prats E, Benito JL, Abós MD, García-López F, Tomás A, et al. [Scintigraphy with 99MTc-HMPAO labeled leukocytes and computed tomography in the diagnosis of vascular graft infection. A comparative study]. Rev Esp Med Nucl. 1999;18(2):77‑83. 26. Agius C, Rakotonirina H, Lacoeuille F, Bouchet F, Vervueren L, Le Jeune J-J, et al. Infection de prothèse vasculaire : 18TEP-FDG vs scintigraphie aux leucocytes marqués (planaires et TEMP/TDM). Médecine Nucl. déc 2011;35(12):628‑40. 27. O’Connor S, Andrew P, Batt M, Becquemin JP. A systematic review and meta-analysis of treatments for aortic graft infection. J Vasc Surg. juill 2006;44(1):38‑45. 28. Saleem BR, Meerwaldt R, Tielliu IFJ, Verhoeven ELG, van den Dungen JJAM, Zeebregts CJ. Conservative treatment of vascular prosthetic graft infection is associated with high mortality. Am J Surg. juill 2010;200(1):47‑52.

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ACCEPTED MANUSCRIPT 29. Teebken OE, Bisdas T, Assadian O, Ricco J-B. Recommendations for Reporting Treatment of Aortic Graft Infections. Eur J Vasc Endovasc Surg. févr 2012;43(2):174‑81.

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30. Czerny M, von Allmen R, Opfermann P, Sodeck G, Dick F, Stellmes A, et al. Self-made pericardial tube graft: a new surgical concept for treatment of graft infections after thoracic and abdominal aortic procedures. Ann Thorac Surg. nov 2011;92(5):1657‑62.

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ACCEPTED MANUSCRIPT HIGHLIGHTS

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Ms. Ref. No.: DMID-16-968

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Title: Graft Infection after a Bentall procedure: a case series and systematic review of the literature.

PET/CT is useful to diagnose BGI but lacks sensitivity and specificity in follow up PET/CT should be interpreted with clinical, biological and radiological parameters If surgery is not possible for BGI, prolonged antibiotic therapy should be followed

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Corresponding Author: Dr. Irene Machelart

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