Anne Coste

Mélanie Poinot

Sophie Panaget

Bénédicte Albert

Adrien Kaladji

Hervé Le Bars

Nasr Bahaa

Badra Ali

Caroline Piau

Matthieu Revest
email: matthieu.revest@chu-rennes.fr

Rozenn Le Berre
email: rozenn.leberre@chu-brest.fr

Use of rifampicin and graft removal are associated with better outcomes in prosthetic vascular graft infection

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction: 66

With a frequency estimated from 1% to 9% [START_REF] O'connor | A systematic review and meta-analysis of 291 treatments for aortic graft infection[END_REF][START_REF] Seeger | Management of patients with prosthetic vascular graft infection[END_REF][START_REF] Darouiche | Treatment of Infections Associated with Surgical Implants[END_REF][START_REF] Anagnostopoulos | Inadequate Perioperative Prophylaxis and Postsurgical Complications After Graft Implantation 298 Are Important Risk Factors for Subsequent Vascular Graft Infections: Prospective Results 299 From the Vascular Graft Infection Cohort Study[END_REF], prosthetic vascular graft infection (PVGI) is 67 a rare complication of vascular surgery associated with severe consequences: the one-year 68 mortality rate ranges from 19.0% to 34.4% [START_REF] Erb | Surgical and antimicrobial 301 treatment of prosthetic vascular graft infections at different surgical sites: a retrospective study 302 of treatment outcomes[END_REF][START_REF] Elens | Management 304 and Outcome of Prosthetic Vascular Graft Infections: A Single Center Experience[END_REF][START_REF] Saleem | Conservative treatment of vascular prosthetic graft infection is associated with high 308 mortality[END_REF][START_REF] Chiesa | Vascular 310 prosthetic graft infection: epidemiology, bacteriology, pathogenesis and treatment[END_REF], and limb amputation can exceed 40% of 69 patients [START_REF] O'hara | Surgical management of infected 313 abdominal aortic grafts: review of a 25-year experience[END_REF]. Despite this heavy clinical burden, many uncertainties still exist regarding the 70 optimal management of this infection. PVGI diagnosis is sometimes hard to ascertain, as no 71 well-defined diagnostic criteria exist. Hence, the conclusions of clinical studies can be biased 72 if rigorous diagnostic criteria are not applied to include real PVGI patients. In addition, the 73 available recommendations on PVGI therapy are only based on small case series and expert 74 opinions [START_REF] Darouiche | Treatment of Infections Associated with Surgical Implants[END_REF][START_REF] Leroy | Vascular graft infections[END_REF][START_REF] Revest | Medical treatment 317 of prosthetic vascular graft infections: Review of the literature and proposals of a Working 318 Group[END_REF][START_REF] Fitzgerald | Diagnosis and treatment of prosthetic aortic graft 320 infections: confusion and inconsistency in the absence of evidence or consensus[END_REF]. Medical and surgical treatments should be combined guided by a 75 multidisciplinary team, but little is known about the specific therapeutic modalities to apply. In 76 situ reconstruction with or without graft removal is now thought to be the best surgical option 77 and is the most frequently performed technique [START_REF] Erb | Surgical and antimicrobial 301 treatment of prosthetic vascular graft infections at different surgical sites: a retrospective study 302 of treatment outcomes[END_REF][START_REF] Batt | A Meta-Analysis of 323 Outcomes After In Situ Reconstructions for Aortic Graft Infection[END_REF]. Proposals on the medical treatment of 78

PVGIs have recently been published, highlighting the need of using molecules active against 79 bacteria embedded inside the biofilm, but the authors regret the lack of solid evidence 80 regarding antimicrobial therapy [START_REF] Revest | Medical treatment 317 of prosthetic vascular graft infections: Review of the literature and proposals of a Working 318 Group[END_REF]. 81 Thus, our study aimed to determine the occurrence of treatment failure in patients with PVGI 82 in a large bicentric retrospective study by using a systematic diagnostic method. Secondarily, 83 we searched for factors associated with treatment failure in multivariate analysis. The two main comorbidities were coronary artery disease (42.0%) and chronic obstructive 121 pulmonary disease (28.6%). 122

The site of infection was a peripheral (n=69), an aorto-thoracic (n=15), an aorto-abdominal 123 (n=24) or an axillo-femoral (n=4) graft. Groin incision was performed at the time of graft 124 implantation in 92 cases (81.4%). Thirty-one patients (27.7%) needed a second surgery for a 125 postoperative non-infectious complication. 126

Diagnosis was made after a median time of 51

Treatment: 146

All patients received antimicrobial therapy. Empirical treatment was given to 76 patients 147 (67.9%), usually a beta-lactam, with an adjunct of an anti-MRSA agent in 46 patients (60.5%). 148

Twenty-seven patients received antibacterial therapy before intraoperative bacterial sampling 149 for a median duration of 6 [START_REF] Darouiche | Treatment of Infections Associated with Surgical Implants[END_REF][START_REF] Anagnostopoulos | Inadequate Perioperative Prophylaxis and Postsurgical Complications After Graft Implantation 298 Are Important Risk Factors for Subsequent Vascular Graft Infections: Prospective Results 299 From the Vascular Graft Infection Cohort Study[END_REF][START_REF] Erb | Surgical and antimicrobial 301 treatment of prosthetic vascular graft infections at different surgical sites: a retrospective study 302 of treatment outcomes[END_REF][START_REF] Elens | Management 304 and Outcome of Prosthetic Vascular Graft Infections: A Single Center Experience[END_REF][START_REF] Saleem | Conservative treatment of vascular prosthetic graft infection is associated with high 308 mortality[END_REF][START_REF] Chiesa | Vascular 310 prosthetic graft infection: epidemiology, bacteriology, pathogenesis and treatment[END_REF][START_REF] O'hara | Surgical management of infected 313 abdominal aortic grafts: review of a 25-year experience[END_REF][START_REF] Leroy | Vascular graft infections[END_REF][START_REF] Revest | Medical treatment 317 of prosthetic vascular graft infections: Review of the literature and proposals of a Working 318 Group[END_REF][START_REF] Fitzgerald | Diagnosis and treatment of prosthetic aortic graft 320 infections: confusion and inconsistency in the absence of evidence or consensus[END_REF][START_REF] Batt | A Meta-Analysis of 323 Outcomes After In Situ Reconstructions for Aortic Graft Infection[END_REF][START_REF] Senneville | Diagnostic des infections sur prothèses vasculaires[END_REF] days. Receiving more than 7 days of antimicrobial treatment 150 before surgery was associated with negative bacterial culture of intraoperative sampling 151 (OR=2.44, p=0.02). This effect was not observed for shorter preoperative treatment durations. 152

The remaining 36 patients were given culture-guided antibiotic therapy directly. 153 A rifampicin combination was used for definite therapy in 31 patients (27.7%), among whom 154 21 were infected with S. aureus, 7 with coagulase negative staphylococci, 1 with 155 Mycobacterium bovis and 2 with a non-documented infection. The median treatment duration 156 was 6 [START_REF] Elens | Management 304 and Outcome of Prosthetic Vascular Graft Infections: A Single Center Experience[END_REF][START_REF] Saleem | Conservative treatment of vascular prosthetic graft infection is associated with high 308 mortality[END_REF][START_REF] Chiesa | Vascular 310 prosthetic graft infection: epidemiology, bacteriology, pathogenesis and treatment[END_REF][START_REF] O'hara | Surgical management of infected 313 abdominal aortic grafts: review of a 25-year experience[END_REF] weeks. Antibiotics were administered for at least 4 weeks in 84 patients (82.6%). 157 Forty patients (40.8%) received antibiotic therapy for more than 6 weeks, including 8 patients 158 (7.1%) receiving suppressive lifelong antimicrobial therapy. 159 Surgical treatment was performed in 96 patients (85.7%). Thirty-eight (33.9%) and ten patients 160 (8.9%) required a second and a third surgery, respectively. The median time between the 161 diagnosis of PVGI and the first surgery was 1 [0-6] day. Microbiological optimal surgery (i.e., 162 total removal of the infected prosthesis) was performed in 48 patients (42.9%). Reconstruction 163 was needed in 60 patients and was performed with an allograft in 20 cases (20/60, 33.3%), an 164 autologous vein in 22 cases (22/60, 36.7%) and prosthetic material in the remaining 18 165 patients. Five patients were treated initially with an endoprosthesis; two of those patients 166 The factors associated with optimal surgery in univariate analysis were peripheral-arterial 169 PVGI vs abdomino-thoracic PVGI (47.9% vs 16.7%, p=0.02), age (63 vs 66 years old, p<0.01), 170 and year of diagnosis (p=0.01). Patients diagnosed with PVGI after 2013 were more likely to 171 undergo the optimal surgery than patients diagnosed in 2013 or before (56.4% vs 35.6%, 172 p=0.04). All-cause mortality did not differ significantly between patients with microbiological 173 optimal and microbiological non-optimal surgery. 174 175

Outcome: 176

All patients but one were followed for more than one year. Three patients (2.7%) and 25 177 patients (22.3%) died during the first 30 days and the first year after PVGI diagnosis, 178 respectively. There were no intraoperative deaths. 179

Treatment failure occurred in 30 patients (27.5%) at one year of follow-up. Death due to PVGI 180 occurred in 12 patients (10.7%), including 3 patients with infection recurrence. Twenty-two 181 patients (19.6%) presented with infection recurrence that occurred before treatment 182 completion in 13 cases. For 6 patients (5.4%), infection recurrence was due to another 183 microorganism and for 15 patients (13.4%) to the same pathogen. The remaining patient 184 successively presented with these two events. The all-cause mortality rate at one year was 185 higher in patients with treatment failure (53.3% vs 10.1%, p<0.01). 186

According to univariate analysis, the factors significantly associated with a lower risk of 187 treatment failure were microbiological optimal surgery (Figure ), rifampicin administration and 188 PVGI diagnostic probability as possible vs certain or probable according to the GRIP criteria 189 (Table 4). No microbiological data were associated with treatment failure. as the Duke criteria used for infective endocarditis [START_REF] Fitzgerald | Diagnosis and treatment of prosthetic aortic graft 320 infections: confusion and inconsistency in the absence of evidence or consensus[END_REF], and an English group of investigators 208 also recently advocated for this [START_REF] Lyons | 333 Diagnosis of Aortic Graft Infection: A Case Definition by the Management of Aortic Graft 334 Infection Collaboration (MAGIC)[END_REF]. However, to the best of our knowledge, no study on PVGI 209 using this kind of diagnostic method has been published so far, and the results of previous 210 studies can therefore be questioned. We based our work on the diagnostic criteria proposed 211 by a French multidisciplinary expert group (GRIP) [START_REF] Senneville | Diagnostic des infections sur prothèses vasculaires[END_REF] to improve the diagnostic accuracy. We 212 included all the patients considered to have a PVGI by their treating physicians and then, we 213 classified all the patients according to the GRIP criteria. PVGI diagnosis likelihood is very high 214 for patients classified as probable and proven PVGI, but quite low for patients with possible 215 PVGI. Besides, treatment failure occurred more frequently in patients diagnosed with proven 216 A c c e p t e d M a n u s c r i p t and probable PVGI than in patients with possible PVGI. Our study reflects the real life: due to 217 the severity of the disease, some patients are treated for PVGI even if the diagnosis is not 218 confirmed. However, our results corroborate the GRIP classification according to diagnostic 219 probability, and we hope that this systematic method could help physicians to manage this 220 hard-to-treat infection. 221

We confirmed that PVGI is a very severe infection, with more than 27% of patients with 222 treatment failure and an all-cause mortality rate of 22% at one year. Our treatment failure rate 223 is similar to that of previous reports [START_REF] Erb | Surgical and antimicrobial 301 treatment of prosthetic vascular graft infections at different surgical sites: a retrospective study 302 of treatment outcomes[END_REF][START_REF] Legout | Factors 337 predictive of treatment failure in staphylococcal prosthetic vascular graft infections: a 338 prospective observational cohort study: impact of rifampin[END_REF][START_REF] Legout | 340 Characteristics and prognosis in patients with prosthetic vascular graft infection: a prospective 341 observational cohort study[END_REF]. PVGI management relies on a multidisciplinary 224 approach and requires antibiotic therapy associated with surgical procedures. The best 225 antimicrobial agents and duration of antibiotic therapy for PVGI remain unknown. Most of our 226 patients were initially treated with a high dosage of intravenous beta-lactam agents as 227 recommended [START_REF] Revest | Medical treatment 317 of prosthetic vascular graft infections: Review of the literature and proposals of a Working 318 Group[END_REF]. It was impossible to capture the impact of the different initial therapeutic 228 options; surgical procedures probably had an initial greater impact than antibiotic treatment, 229 but we found that the use of rifampicin was associated with a better outcome. This has already 230 been demonstrated for joint-prosthesis infection [START_REF] Senneville | Outcome and 344 predictors of treatment failure in total hip/knee prosthetic joint infections due to Staphylococcus 345 aureus[END_REF] and for PVGI [START_REF] Erb | Surgical and antimicrobial 301 treatment of prosthetic vascular graft infections at different surgical sites: a retrospective study 302 of treatment outcomes[END_REF][START_REF] Legout | Factors 337 predictive of treatment failure in staphylococcal prosthetic vascular graft infections: a 338 prospective observational cohort study: impact of rifampin[END_REF]. Rifampicin offers 231 many advantages in difficult-to-treat infections: high biodisponibility, a large diffusion capacity, 232 a large spectrum on gram-positive cocci, intense bactericidal activity even on intracellular 233 bacteria [START_REF] Boudjemaa | Live 347 intramacrophagic Staphylococcus aureus as a potential cause of antibiotic therapy failure: 348 observations in an in vivo mouse model of prosthetic vascular material infections[END_REF], and on bacteria with altered metabolic state inside the biofilm [START_REF] Zheng | Penetration of Rifampin through Staphylococcus epidermidis 351 Biofilms[END_REF][START_REF] Boudjemaa | 353 New Insight into Daptomycin Bioavailability and Localization in Staphylococcus aureus 354 Biofilms by Dynamic Fluorescence Imaging[END_REF]. In our 234 work, the rifampicin effect was not differentiated according to the causative pathogen because 235 of the small sample size. However, rifampicin was essentially used for S. aureus PVGI, and 236 our results add another building block for its importance in material-related S. aureus 237

infections. 238

One other question regarding the treatment of PVGI refers to the duration of antibiotic therapy. 239

Available data only come from non-comparative studies whose objectives were not the 240 evaluation of treatment duration. Most of those publications report 6 or 12 weeks of treatment, 241 but others report shorter or longer antibiotic therapy. In our study, most patients received 242 antibiotics for 6 weeks, regardless of whether the surgical treatment was optimal. The survival 243 A c c e p t e d M a n u s c r i p t and treatment failure rates were similar to those of other cohorts, and we did not find any 244 impact of treatment duration on treatment failure. Thus, 6-week-long treatment seem to be 245 long enough for PVGI. 246 A negative effect of more than 7 days of preoperative antimicrobial therapy was found on the 247 bacterial growth of intraoperative samples. This effect was not observed for shorter treatments 248 but could be different according to the pathogens and antimicrobial drugs. To minimize the risk 249 of perioperative sample culture negativity, preoperative antibiotic therapy should be reserved 250 for patients with sepsis. 251 Several techniques have been proposed for the surgical treatment of PVGI. Similar to osteo-252 articular infection, total removal of the entire infected graft is encouraged [START_REF] Darouiche | Treatment of Infections Associated with Surgical Implants[END_REF][START_REF] Legout | 356 Diagnosis and management of prosthetic vascular graft infections[END_REF]. This statement 253 is supported by little proof [START_REF] Saleem | Conservative treatment of vascular prosthetic graft infection is associated with high 308 mortality[END_REF][START_REF] Maze | Outcomes of 359 infected abdominal aortic grafts managed with antimicrobial therapy and graft retention in an 360 unselected cohort[END_REF], and some studies have not found this positive impact [START_REF] Erb | Surgical and antimicrobial 301 treatment of prosthetic vascular graft infections at different surgical sites: a retrospective study 302 of treatment outcomes[END_REF], 254 sometimes even demonstrating a negative effect [START_REF] Calligaro | 362 Selective preservation of infected prosthetic arterial grafts. Analysis of a 20-year experience 363 with 120 extracavitary-infected grafts[END_REF]. Our study supports the need for this 255 microbiological optimal surgical treatment in multivariate analysis. However, complete graft 256 excision is not always possible or can be associated with poor functional results. The choice 257 of surgical treatment may be guided by the operability of the patient and therefore may be 258 correlated with the risk of mortality and induced morbidity. In our study, 85.7% of patients 259 underwent surgery, and 42.9% of patients underwent microbiological optimal surgery with total 260 removal of the infected vascular prosthesis. Most recent studies reported complete excision of 261 the infected prosthetic vascular graft in 22.9% to 85.5% of cases [START_REF] Erb | Surgical and antimicrobial 301 treatment of prosthetic vascular graft infections at different surgical sites: a retrospective study 302 of treatment outcomes[END_REF][START_REF] Elens | Management 304 and Outcome of Prosthetic Vascular Graft Infections: A Single Center Experience[END_REF][START_REF] Saleem | Conservative treatment of vascular prosthetic graft infection is associated with high 308 mortality[END_REF][START_REF] Legout | 340 Characteristics and prognosis in patients with prosthetic vascular graft infection: a prospective 341 observational cohort study[END_REF]. In our study, 262 microbiological optimal surgery was more frequently performed in young patients with 263 peripheral-arterial surgery but did not depend on one specific comorbidity. The surgical rates 264 increased every year. One explanation for this increasing rate is the recent improvements in 265 surgical techniques and in anaesthesiology. Performing optimal surgery is now an option in 266 patients who would have been previously recused. Second, in both participating centres, a 267 multidisciplinary team that included infectious disease clinicians, surgeons and bacteriologists 268 was established during the study period.

M a n u s c r i p t

There were several limitations in this study. First, this was a retrospective study with all the 270 associated limitations. However, we used a recognized definition of PVGI using criteria 271 systematically recorded when taking care of patients with PVGI. Thus, we only included 272 patients with a high probability of PVGI. In addition, missing data were very rare, and we were 273 able to collect one-year follow-up data for all the patients except one. Moreover, due to the 274 scarcity of the disease and the vast heterogeneity of patients, it is very difficult to conduct 275 prospective multicentre studies in this field. Retrospective cohort studies such as ours are 276 probably the least incorrect option to improve our knowledge about this very severe disease. 277

Second, this study included patients with various surgical and medical approaches, but this 278 reflects the vast heterogeneity of PVGI patient management. We aimed to describe the classic 279 care of patients with PVGI in real life to draw interesting conclusions in daily practice.

  all authors, the corresponding author states that there is no conflict of interest 31

  A c c e p t e d M a n u s c r i p t required another surgery for total replacement with an allograft. Limb amputation was 167 performed in 18 cases (16.8%). 168

  190

A c c e

  p t e d M a n u s c r i p t All three factors remained independently associated with a lower risk of treatment failure in the 191 multivariate analysis: microbiological optimal surgery (OR=0.22 [0.07-0.57], p<0.01), possible 192 PVGI according to the GRIP criteria compared to probable and proven PVGI (OR=0.27 [0.07-193 0.85], p=0.04), and rifampicin administration (OR=0.30 [0.09-0.87], p=0.04). As the diagnosis 194 of PVGI for the patients classified in the "possible" group could be uncertain, we performed 195 another multivariate analysis including only the patients with probable or proven PVGI: 196 microbiological optimal surgery and rifampicin administration remained significantly associated 197 with a better outcome. 198 199 Discussion: 200 Important information comes from this large bicentric retrospective study: i) treatment failure 201 occurred in 27.5% of 112 patients and was associated with a high mortality rate of 53.3% at 202 one year; ii) use of a rifampicin-combined regimen was associated with a better outcome; and 203 iii) removal of the entire infected material also. 204 The lack of clear validated diagnostic criteria to define PVGI represents one of the most 205 problematic issues for improving patient management and literature analysis. In a pioneering 206 study published in 2005, Fitzgerald et al argued for a provisional set of diagnostic criteria, such 207

  269

A c c e p t e d

  In conclusion, PVGI, a biofilm-associated infection, is associated with a high risk of treatment 283 failure. In this retrospective study, complete excision of the infected graft and rifampicin 284 administration were associated with favourable outcomes. As complete excision of the graft 285 constitutes a major surgery, PVGI diagnosis should be based on a recognized definition. Our 286 study demonstrated the reliability of the GRIP criteria for diagnosis. Prospective studies using 287 such a definition of PVGI are needed to clarify the best PVGI management choices. 288 289 A c c e p t e d M a n u s c r i p t

Figure

  Figure

  Inclusion All the patients treated for PVGI in the Brest University Hospital, France, between 89 January 2011 and June 2016 or in the Rennes University Hospital, France, between January 90 December 2014 were included in this retrospective cohort study. Patients were 91 identified using the French hospital discharge database. Patients with infection of a biological 92 graft, a coronary graft or stent, a vascular patch, or a vascular endoprosthesis were excluded. 93 Definition of PVGI PVGI was defined according to the Groupe de Réflexion sur les Infections 94 de Prothèses Vasculaires (GRIP) criteria[START_REF] Senneville | Diagnostic des infections sur prothèses vasculaires[END_REF], displayed in Table1. Patients were classified 95 according to the likelihood of PVGI: possible, probable or proven. 96 Outcome definition Treatment failure was a composite clinical criterion defined as the 97 occurrence of one of the following events within the first year after PVGI diagnosis: death due 98 to PVGI and infection recurrence due to the same or another pathogen during antimicrobial 99 treatment or after treatment completion. Mortality due to PVGI was assessed by two 100 independent physicians (MP, SP); in the case of disagreement, the opinion of a third physician 101 was sought (RLB or MR). Treatment failure was diagnosed according to the GRIP criteria of 102 PVGI at least 7 days after the initial PVGI diagnosis. Descriptive data were expressed as medians [25 th -75 th percentiles] for 104 continuous variables and as numbers (percentages) for categorical variables. Factors were 105 tested for association with treatment failure with non-parametric tests. Fisher's exact test was 106 used for categorical variables, and the Wilcoxon rank sum test was used for continuous 107 variables. Factors associated with treatment failure in univariate analysis (p≤0.2) were entered 108 into a multivariate logistic regression model. Variable selection was performed using backward 109 and forward selection (p≤0.05). Adjusted odds ratios were obtained with their 95% confidence 110

	84 85 86 87 88 A c c e p t e d Methods: Ethics The Brest and Rennes ethics committees approved this observational study under reference numbers 2018CE.21 and 1585, respectively. M a n u s c r i p t 111 112 Results: 113 A c c e p t e d One hundred and twelve patients (81.3% men) were diagnosed with possible, probable and 115 proven PVGI in 26 (23.2%), 22 (19.6%) and 64 cases (57.1%), respectively. Clinical 116 characteristics and prognosis of patients according to the likelihood of PVGI are displayed in 117 the supplementary table. Forty patients (35.7%) were treated at the Brest University Hospital, 118 and 72 patients (64.3%) in Rennes. The median age was 66 [60-75] years (Table 2). The main 119 2005 and interval [OR (95% CI)]. Analysis was performed using R statistical software, version 3.4.4 [15]. M a n u s c r i p t cardiovascular risk factors were active smoking (84.3%) and arterial hypertension (60.7%). 120
	114	Population:

103

Statistical analysis

and contributed to the diagnosis in 89.7% of cases, whereas Doppler was performed 131 in 15 patients (13.4%) and contributed to diagnosis in 80.0% of cases. Patients with aortic 132 PVGI presented more frequently with fever than patients with peripheral PVGI (78.6% vs 133

  days after graft implantation. At the 127 Coxiella burnetti was documented with positive serology. The most frequent 139 pathogens are displayed in Table 3 and were gram-positive cocci (62.5%), including 140 Staphylococcus aureus (27.3%) and Enterococcus sp. (14.6%); gram-negative bacilli (26.4%); 141and anaerobes (7.7%). The anatomical site of the PVGI did not influence the spectrum of 142 infecting agents and patients with polymicrobial infections did not suffer more frequently from 143 postoperative wound healing disorders than patients with monomicrobial infections.

	144
	128 129 145	time of diagnosis, all patients but three (97.3%) presented with a clinical sign, mainly pain (65.9%) and fever (62.0%). The C-reactive protein level was >10 mg/L for 92.3% of patients. M a n u s c r i p t
	Leucocytes were >10 G/L for 67.1% of patients. A CT scan was performed in 58 patients (51.8%) 51.5%, p<0.01) and less frequently with local erythema (34.3% vs 65.0%, p<0.01). Infections were microbiologically documented in 91 patients (81.3%), including 37 patients with polymicrobial infection (40.7%). Among patients undergoing surgery with intraoperative bacterial sampling (n=92), 71 (77.2%) had a positive bacterial culture. Blood culture was performed in 53 patients (47.3%), and 33 (62.3%) cultures yielded a positive result. One infection due to A c c e p t e d 130 134 135 136 137 138

Table 1 . Groupe de Réflexion sur les Infections de Prothèses Vasculaires (GRIP) diagnostic criteria

 1

	Table
	2
	3
	Proven PVGI:
	Two criteria among the following are required:
	 positive smear or culture of intra-operative samples of the vascular prosthesis or periprosthetic tissues  periprosthetic suppuration  presence of collections or periprosthetic air bubbles after eight postoperative weeks  vascular prosthesis exposition through wound or gut Probable PVGI: Two clinical criteria among the following are required:  fever, shaking chills, septic shock, or haemorrhagic shock due to aorto-digestive fistula or anastomotic rupture of the bypass  local pain  erythema  local tumefaction  suppurative fistula  abscess or lack of vascular material integration (except PTFE implant) And a microbiological criterion:  one positive blood culture M a n u s c r i p t
	 if commensal flora bacteria are isolated, two positive haemocultures are required Or a radiological criterion:  presence or persistence of collection and/or periprosthetic air bubbles after 8 postoperative weeks  abscess  false aneurysm Possible PVGI: One criterion among the following is required  a clinical criterion (as listed above)  a biological criterion: C-reactive protein level more than 10 mg/L and/or hyperleukocytosis more than 10 g/L  a radiological criterion (as listed above) A c c e p t e d

Table 2 . Population characteristics

 2

		Treatment success	Treatment
	Characteristics	(n=82)	failure (n=30)	Total (n=112)
	Men, n (%)	68 (82.9)	23 (77.7)	91 (81.3)
	Age (years), median [IQ1-IQ2) Diabetes mellitus, n (%) Chronic obstructive pulmonary disease, n (%) Arterial hypertension, n (%) Coronary artery disease, n (%) Solid cancer, n (%) Stroke, n (%) Severe renal insufficiency, n (%) Immunosuppression, n (%) Active smoking, n (%) Presentation at time of diagnosis Fever, n (%) Local pain, n (%) Local erythema, n (%) Fistula or swelling, n (%) Scar disunion, n (%) M 65 [59-73] 18 (22.0) 23 (28.1) 49 (60.5) 33 (40.2) 20 (24.4) 13 (15.9) 15 (18.3) 10 (12.2) 56 (86.2) 50/79 (63.3) 41/60 (68.3) 37/70 (52.9) 40/76 (52.6) 35/76 (46.1) a n u s c r i p t 67 [61-78] 66 [60-75] 10 (33.3) 28 (25.0) 9 (30.0) 32 (28.6) 19 (63.3) 68 (60.7) 14 (47.7) 47 (42.0) 5 (17.7) 25 (22.3) 2 (6.7) 15 (13.4) 7 (24.1) 22 (19.6) 5 (16.7) 15 (13.4) 19 (79) 75 (84.3) 17/29 (58.6) 67/108 (62.1) 13/24 (59.1) 54/82 (65.9) 14/25 (56.0) 51/95 (53.7) 17/28 (60.7) 57/104 (54.8) 9/25 (36.0) 44/101 (43.6)
	White blood count > 10 G/L, n (%) C-reactive protein > 10 mg/L, n (%) A c c e p t e d	47/73 (64.4) 38/42 (90.5)	18/24 (75.0) 15/15 (100)	65/97 (67.0) 53/59 (93.0)

Table 3 . Microbiological data

 3

	Bacterial documentation per	N (%)
	patient Bacterial documentation	91/112
	Polymicrobial PVGI	(81.3)
	Positive preoperative samples	37/112
	Positive blood samples	(33.0) 71/96
		(74.0) 33/52
	Microorganisms isolated	(63.5) 144 (100)
	(n=144) Aerobic Gram-positive	90 (62.5)
	bacteria Methicillin-sensitive Staphylococcus	36 (25.0)
	aureus Methicillin-resistant	3 (2.1)
	Staphylococcus aureus Coagulase-	17 (11.8)
	negative staphylococci Enterococcus sp.	21 (14.6)
	Streptococcus sp.	13 (9.0)
	Aerobic Gram-negative bacilli	38 (26.4)
	Escherichia coli	12 (8.3)
	Pseudomonas	7 (4.9)
	aeruginosa Various	19 (13.2)
	Anaerobes	11 (7.7)
	Candida	1 (0.7)
	sp. Others	4 (2.8)

Table 4 . Factors associated with poor outcome in univariate and multivariate analyses p-value OR [95% CI] p-value

 4

	0.018 0.22 [0.07-0.57]	p<0.01
	0.1	0.30 [0.09-0.87]	0.04

Supplementary table. Population characteristics according to GRIP definition of PVGI Characteristics Total (n=112)

			Proven or probable	Possible
			PVGI (n=86)	PVGI (n=26) P-value
	Men, n (%)	91 (81.3)	73 (84.9)	18 (69.2)	NS
	Age (years), median [IQ1-IQ2]	66 [60-75]	66 [60-75]	61 [59-73]	<0.05
	Diabetes mellitus, n (%)	28 (25.0)	24 (27.9)	4 (15.4)	NS
	Chronic obstructive pulmonary disease,
	n (%) Arterial hypertension, n (%) Coronary artery disease, n (%) Solid cancer, n (%) Stroke, n (%) Severe renal insufficiency, n (%) Immunosuppression, n (%) Active smoking, n (%) Initial surgery Peripheral PVGI, n (%) Groin incision Presentation at time of diagnosis Fever, n (%) Local pain, n (%) Local erythema, n (%) Fistula or swelling, n (%)	32 (28.6) 68 (60.7) 47 (42.0) 25 (22.3) 15 (13.4) 22 (19.6) 15 (13.4) 75 (84.3) 69 (61.6) 92 (81.4) 67/108 (62.1) 54/82 (65.9) 51/95 (53.7) 57/104 (54.8) M a n u s c r i p t 23 (26.7) 9 (34.6) NS 51 (60.0) 17 (65.4) NS 38 (44.2) 9 (34.6) NS 19 (22.1) 6 (23.1) NS 14 (16.3) 1 (3.8) NS 17 (20.0) 5 (19.2) NS 12 (14.0) 3 (11.5) NS 59 (83.1) 16 (88.9) NS 54 (62.8) 15 (57.7) NS 70 (82.6) 21 (80.8) NS 54 (65.1) 13 (52.0) NS 44 (65.7) 10 (66.7) NS 40 (54.1) 11 (52.4) NS 47 (58.0) 10 (43.5) NS
	Scar disunion, n (%) White blood count > 10 G/L, n (%) C-reactive protein > 10 mg/L, n (%) Microbiological documentation, n (%) Polymicrobial infection, n (%) Treatment and outcome Rifampicin-based regimen, n (%) Antimicrobial therapy for 6 weeks or more, n (%) Optimal surgery, n (%) Death at one year, n (%) Treatment failure, n (%) A c c e p t e d 44/101 (43.6) 65/97 (67.0) 53/59 (93.0) 91 (81.3) 37 (33.0) 31 (27.7) 40 (40.8) 48 (42.9) 25 (22.3) 30 (27.5) 17	33 (42.3) 51 (68.0) 41 (93.2) 78 (90.7) 30 (34.9) 25 (29.1) 32 (41.6) 41 (47.7) 20 (23.5) 26 (31.3)	11 (47.8) 14 (63.6) 12 (92.3) 13 (50) 7 (26.9) 6 (23.1) 8 (38.1) 7 (26.9) 5 (19.2) 4 (15.4)	NS NS NS <0.05 NS NS NS NS NS NS