management of aortic graft infections & opat dr nick...
TRANSCRIPT
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Management ofAortic Graft Infections & OPAT
Dr Nick Price
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Management of Aortic Graft Infection & OPAT
Dr Nicholas PriceDirectorate of InfectionGuy’s & St Thomas’ NHS Foundation Trust
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Talk outline
1. BACKGROUND– What’s the evidence?– What’s a case?
2. INVESTIGATIONS– Microbiology– Imaging
3. MANAGEMENT– Surgical– Medical (OPAT)
4. CONCLUSIONS
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Background
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Current consensus
§ Rare condition: aortic graft insertion complicated by infection in 0.5-6%§ Serious: ≈100% mortality in 2-3 years§ Diagnosis made by a combination of clinical, surgical, radiological and
laboratory findings§ Complete surgical removal of the infected prosthesis is highly desirable§ Use infection resistant graft material/conduit§ Antimicrobial therapy is a vital adjunct to surgery
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Search terms:1. Vascular2. Aort*3. Endo*4. 1 OR 2 OR 35. Graft*6. Stent7. 5 AND 68. Infection*9. 4 AND 7 AND 810. Management11. Treatment12. Surg*13. 10 AND 11 AND 1214. 4 AND 9 AND 13
*Terms starting searched.
Databases searches:Medline, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library.
Types of studies included:• Randomised control trials (RCT)• Controlled clinical trials (CCTs)• Interrupted time series with ≥ 3 data points before & after
implementation of the intervention (ITS)• Controlled before & after studies (CBA).
Limiters:• Human studies• English language publications• 1/1/05 – 22/6/16
Diagnosis & management of vascular graft infectionJenkins A, Sandoe J, Price N, Bell R (2016)
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Diagnosis & management of vascular graft infectionPROSPERO International prospective register of systematic reviews 2016
http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016038759
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Complete removal of infected prostheses not easy…20-30% mortality
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The evidence
• No RCTs - better surgical studies are large case series• Animal studies• Radiological data descriptive• Microbiological brief and insufficient• No well-designed trials of optimum antimicrobial agents, method of
administration, duration of treatment• No reference to a diagnostic standard• No clinical guidelines
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Case definition
• Essential for entry into trials or case registries and evaluation of published data
• Management of Aortic Graft Infection Collaboration– Established 2012– Vascular surgeons, imaging & infection specialists – Birmingham Heartlands, Guy’s & St Thomas’, Leeds, Imperial, Royal
Free, University Hospital South Manchester– First ever case definition - derived by expert consensus/ modified
Delphi method– Definition used to determine entry to service evaluation database
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Aortic Graft Infection Diagnosis: A case Definition by theManagement of Aortic Graft Infection Collaboration (MAGIC)
OTA Lyons et al, European Journal of Vasc & Endovasc Surg 2016: 52, 758-763
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Microbiology
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Pathogenesis of aortic graft infection
Microorganisms colonise vascular grafts by:1. contamination at the time of surgery2. direct extension from an adjacent site3. haematogenous seeding (bacteraemia)
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Aortic Graft Infection Diagnosis: A case Definition by theManagement of Aortic Graft Infection Collaboration (MAGIC)
OTA Lyons et al, European Journal of Vasc & Endovasc Surg 2016: 52, 758-763
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Standardised intra-operative sampling methodology
Courtesy of Dr Stephanie Thomas, Univ. Hosp. South Manchester
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0
5
10
15
20
25
Candida s
pp.
Enterobacter c
loacae
Enterococcu
sE. co
li
Other gut o
rgs
Pseudomonas
Mycobacte
ria sp
p.
Staph. a
ureus
Coag neg.
Staph.
Strep. sp
p.
Misc. n
on-gut o
rgs
Aortic graft infection: causative organisms
41% polymicrobial
No.
of t
imes
isol
ated
75/85 patients (88%) had positive microbiology
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Courtesy of M Sallam
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Candida spp.2% Enterococcus
8%
E. coli17%
Other gut orgs6%
Pseudomonas6%
Staph. aureus15%
Coag neg. Staph.25%
Strep. spp.8%
Misc. non-gut orgs13%
Candida spp.17%
Enterobacter cloacae
11%
Enterococcus17%
E. coli8%
Other gut orgs15%
Staph. aureus6%
Coag neg. Staph.15%
Misc. not-gut orgs11%
Aorto-enteric/oesophageal fistulae
NO FISTULAPolymicrobial 33%
FISTULAPolymicrobial 65%
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Presentation vs Pathogen
Onset Organism Presentation
EARLY(<4/12) S. aureus
• Acute, fulminant, fever• Wound infection• Graft dysfunction e.g. bleeding, thrombosis• Positive BC
LATE(>4/12)
Skin flora (CNS)(polymicrobial)
• Indolent, no fever• Graft complications e.g. fistula, false aneurysm etc• Negative BC• Biofilm formation
Seabrook et al, 1990, J Vasc Surg
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Early vs Late infection
0
2
4
6
8
10
12
14
Candida sp E coli Enterococci Other GutFlora
S aureus CoNS Misc Negative
Early Graft Infection
Late Graft Infection
31 early: 28 late
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Pneumococcal mycotic aneurysms
Patient Sample type Culture result(Penicillin MIC) Molecular result
1 Blood Culture Strep. pneumoniae (<0.06 mg/L) -
2 Blood cultureStrep. pneumoniae
Serotype 23B(0.25 mg/L)
-
3
Aneurysm tissue Negative Strep. pneumoniae pbp-2b target NOT detected: penicillin RESISTANCE?
Aneurysm tissue Negative Strep. pneumoniae lytA gene detected: penicillin RESISTANCE?
Vertebral body/disc biopsy CNS only Strep. pneumoniae lytA gene
detected: penicillin RESISTANCE?
4 Pus (leg) Negative Strep. pneumoniae lytA gene detected: penicillin SUSCEPTIBILITY?
Seet et al, Ann Vasc Surg. 2019
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Q fever
SUVmax 8.2CRP 56Phase 1: IgG 1:5120; IgA 1:1280Phase 2: IgM negative
6 months: SUVmax 3.8CRP 1
4 months: Phase 1: IgG 1:5120; IgA 1:640Phase 2: IgM negative
Pre-treatment After doxy + HCQ
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Imaging
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Aortic Graft Infection Diagnosis: A case Definition by theManagement of Aortic Graft Infection Collaboration (MAGIC)
OTA Lyons et al, European Journal of Vasc & Endovasc Surg 2016: 52, 758-763
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Imaging: CT
• Sensitivity 55-100% /Specificity 85-100%• Depends on what diagnostic criteria and how advanced?• Peri-graft fluid at ≥3 months• Peri-graft gas (fistula or gas-forming organisms) at ≥4-7 weeks • Pseudoaneurysm in 25%• Local complications:
– Discitis– Hydronephrosis– Bowel wall thickening (fistula?)
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Peri-graft fluid
Orton DF, et al. Aortic Prosthetic Graft Infections RadioGraphics 2000; 20:977–993
Early post-op fluid and absorption at 1 year
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Peri-graft gas
Aorto-bronchial fistula
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Discitis/vertebral osteomyelitis
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FDG PET-CT
Dr Tara Barwick, Imperial College
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• 34 cases of suspected AGI• Combined functional &
morphological PET CT analysis:– Intensity of FDG uptake (SUVmax)– Uptake pattern along the graft i.e.
focal vs. diffuse– Suggestive CT findings e.g. fluid, gas
• Results– Sensitivity 100%; Specificity 86%– PPV 96%; NPV 100%; Accuracy 97%
5 point scale:1. Normal background activity2. Mildly increased BUT diffuse3. Focal BUT mild OR strong diffuse4. Focal AND intense (+/- diffuse)5. Focal intense AND fluid collection
Useful for monitoring response to antibiotic therapy?
Diagnostic Performance of 18F-FDG-PET/CT in Vascular Graft Infections
B.-R. Sah a,e, L. Husmann a,e, D. Mayer b, A. Scherrer c, Z. Rancic b, G. Puippe d, R. Weber c, B. Hasse c,*, the Vasgra Cohorta Department of Medical Radiology, Division of Nuclear Medicine, University Hospital of Zurich, Zurich, Switzerlandb Clinic for Cardiovascular Surgery, University Hospital and University of Zurich, Zurich, Switzerlandc Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Zurich, Switzerlandd Institute of Diagnostic and Interventional Radiology, Department Medical Radiology, University Hospital of Zurich, Zurich, Switzerland
WHAT THIS PAPER ADDSThis study introduces a new visual grading score that improves the accuracy of FDG-PET/CT in the detection ofprosthetic vascular graft infections (PVGIs). This will not only improve and speed up the diagnosis of PVGI butalso allow for the monitoring of medical and surgical therapy thereof. Morbidity, mortality, and costs oftreatment may signi!cantly decrease in the near future because of the enhanced diagnostic accuracy andimproved therapeutic management.
Objective: The aim of this study was to evaluate the diagnostic accuracy of positron emission tomography/computed tomography with 18F-"udeoxyglucose (FDG-PET/CT) in a population with suspected graft infection andto validate a new diagnostic imaging score for FDG-PET/CT.Methods: This was a prospective cohort study. FDG-PET/CT was performed prospectively in 34 patients withsuspected graft infection, in 12 of them before the start of antimicrobial treatment. Diagnostic accuracy wasassessed using a new !ve point visual grading score and by using a binary score. Maximum standardized uptakevalues (SUVmax) were calculated for quantitative measurements of metabolic activity, and cut off points werecalculated using the receiver operator curve (ROC). The standard of reference was a microbiological culture,obtained after open biopsy or graft explantation.Results: Using the new scale, FDG-PET/CT correctly recognized 27 patients with graft infection, one patient wasdiagnosed as false positive, six patients were correctly classi!ed as true negative, and no patients were ratedfalse negative. Hence, sensitivity, speci!city, positive predictive value (PPV), negative predictive value (NPV), andaccuracy of FDG-PET/CT for the diagnosis of graft infections were 100%, 86%, 96%, 100%, and 97%, respectively.Using a previously established binary score, sensitivity, speci!city, PPV, NPV, and accuracy were 96%, 86%, 96%,86%, and 94% respectively. ROC analysis suggested an SUVmax cut off value of !3.8 to differentiate betweeninfected and non-infected grafts (p < .001). Additionally, FDG-PET/CT provided a conclusive clinical diagnosis insix of seven patients without graft infection (i.e., other sites of infections).Conclusions: The diagnostic accuracy of FDG-PET/CT in the detection of aortic graft infection is high. A newlyintroduced !ve point visual grading score and early imaging prior to antimicrobial treatment may further improvethe diagnostic accuracy.! 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.Article history: Received 2 September 2014, Accepted 15 December 2014,Keywords: Positron emission tomography/computed tomography, Graft infection, Fludeoxy glucose
INTRODUCTION
Vascular graft infections, although relatively rare (incidencerate between 1% and 6%)1 require an immediate and de!nitediagnosis2 as they carry a high mortality and morbidity risk.3
In 2005, a !rst report on the diagnostic accuracy of positronemission tomography/computed tomography (PET/CT) with
18F-"udeoxyglucose (FDG) suggested an increased accuracyof FDG-PET/CT compared with the current standard contrastenhanced CT in the diagnostic assessment of patients withsuspected vascular graft infection.4 Since then other groupshave recon!rmed the higher sensitivity of PET/CT in thedetection of graft infections.4e7
Signs of graft infection on PET/CT imaging are "uid for-mations or fat stranding and/or FDG avid lesions adjacent tothe graft, as FDG accumulates in metabolically active cellsand thus detects infectious tissues.8 Increased glucosemetabolism may be detected earlier and/or in less severestages of infectious processes by PET/CT than graft thick-ening, perigraft soft tissue enhancement, pseudoaneurysmformation, or gas collection typically detected by CT imaging,
e These authors contributed equally.* Corresponding author. B. Hasse, Division of Infectious Diseases and
Hospital Epidemiology, University and University Hospital Zurich, Raemis-trasse 100, CH-8091 Zurich, Switzerland.E-mail address: [email protected] (B. Hasse).1078-5884/! 2014 European Society for Vascular Surgery. Published by
Elsevier Ltd. All rights reserved.http://dx.doi.org/10.1016/j.ejvs.2014.12.024
Eur J Vasc Endovasc Surg (2015) 49, 455e464
Diagnostic Performance of 18F-FDG-PET/CT in Vascular Graft Infections
B.-R. Sah a,e, L. Husmann a,e, D. Mayer b, A. Scherrer c, Z. Rancic b, G. Puippe d, R. Weber c, B. Hasse c,*, the Vasgra Cohorta Department of Medical Radiology, Division of Nuclear Medicine, University Hospital of Zurich, Zurich, Switzerlandb Clinic for Cardiovascular Surgery, University Hospital and University of Zurich, Zurich, Switzerlandc Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Zurich, Switzerlandd Institute of Diagnostic and Interventional Radiology, Department Medical Radiology, University Hospital of Zurich, Zurich, Switzerland
WHAT THIS PAPER ADDSThis study introduces a new visual grading score that improves the accuracy of FDG-PET/CT in the detection ofprosthetic vascular graft infections (PVGIs). This will not only improve and speed up the diagnosis of PVGI butalso allow for the monitoring of medical and surgical therapy thereof. Morbidity, mortality, and costs oftreatment may signi!cantly decrease in the near future because of the enhanced diagnostic accuracy andimproved therapeutic management.
Objective: The aim of this study was to evaluate the diagnostic accuracy of positron emission tomography/computed tomography with 18F-"udeoxyglucose (FDG-PET/CT) in a population with suspected graft infection andto validate a new diagnostic imaging score for FDG-PET/CT.Methods: This was a prospective cohort study. FDG-PET/CT was performed prospectively in 34 patients withsuspected graft infection, in 12 of them before the start of antimicrobial treatment. Diagnostic accuracy wasassessed using a new !ve point visual grading score and by using a binary score. Maximum standardized uptakevalues (SUVmax) were calculated for quantitative measurements of metabolic activity, and cut off points werecalculated using the receiver operator curve (ROC). The standard of reference was a microbiological culture,obtained after open biopsy or graft explantation.Results: Using the new scale, FDG-PET/CT correctly recognized 27 patients with graft infection, one patient wasdiagnosed as false positive, six patients were correctly classi!ed as true negative, and no patients were ratedfalse negative. Hence, sensitivity, speci!city, positive predictive value (PPV), negative predictive value (NPV), andaccuracy of FDG-PET/CT for the diagnosis of graft infections were 100%, 86%, 96%, 100%, and 97%, respectively.Using a previously established binary score, sensitivity, speci!city, PPV, NPV, and accuracy were 96%, 86%, 96%,86%, and 94% respectively. ROC analysis suggested an SUVmax cut off value of !3.8 to differentiate betweeninfected and non-infected grafts (p < .001). Additionally, FDG-PET/CT provided a conclusive clinical diagnosis insix of seven patients without graft infection (i.e., other sites of infections).Conclusions: The diagnostic accuracy of FDG-PET/CT in the detection of aortic graft infection is high. A newlyintroduced !ve point visual grading score and early imaging prior to antimicrobial treatment may further improvethe diagnostic accuracy.! 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.Article history: Received 2 September 2014, Accepted 15 December 2014,Keywords: Positron emission tomography/computed tomography, Graft infection, Fludeoxy glucose
INTRODUCTION
Vascular graft infections, although relatively rare (incidencerate between 1% and 6%)1 require an immediate and de!nitediagnosis2 as they carry a high mortality and morbidity risk.3
In 2005, a !rst report on the diagnostic accuracy of positronemission tomography/computed tomography (PET/CT) with
18F-"udeoxyglucose (FDG) suggested an increased accuracyof FDG-PET/CT compared with the current standard contrastenhanced CT in the diagnostic assessment of patients withsuspected vascular graft infection.4 Since then other groupshave recon!rmed the higher sensitivity of PET/CT in thedetection of graft infections.4e7
Signs of graft infection on PET/CT imaging are "uid for-mations or fat stranding and/or FDG avid lesions adjacent tothe graft, as FDG accumulates in metabolically active cellsand thus detects infectious tissues.8 Increased glucosemetabolism may be detected earlier and/or in less severestages of infectious processes by PET/CT than graft thick-ening, perigraft soft tissue enhancement, pseudoaneurysmformation, or gas collection typically detected by CT imaging,
e These authors contributed equally.* Corresponding author. B. Hasse, Division of Infectious Diseases and
Hospital Epidemiology, University and University Hospital Zurich, Raemis-trasse 100, CH-8091 Zurich, Switzerland.E-mail address: [email protected] (B. Hasse).1078-5884/! 2014 European Society for Vascular Surgery. Published by
Elsevier Ltd. All rights reserved.http://dx.doi.org/10.1016/j.ejvs.2014.12.024
Eur J Vasc Endovasc Surg (2015) 49, 455e464
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Surgical management
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Surgical strategies• Objectives of surgery
– Sepsis source control– Re-establish circulation
• Tube grafts– Extra-anatomical or in situ (anatomical)?– Material - biological/artificial?
• Stent grafts/ EVAR– Transformational - less invasive– Temporizing or ‘bridging’ stent
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13 abdominal stents• 10 infra-renal devices explanted (AxBifem)• 70% survived median 29 (range 12-45) months
9 thoracic stents• All retained/ 3 extended for rupture• 7 patients dead by 24 months
14-year experience with aortic endograft infectionLyons OTA et al, Eur. J. Vasc. Endovasc. Surg. 2013, 45(3): 306-313
100% overall mortality from aortic disease with retention; 10/12 dead ≤15 months
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Extra-anatomical repair
• Axillo-bifemoral bypass + oversew of aorta• Bilateral axillo-femoral & axillo-SFA/popliteal bypass• Long operation• Patency:
– ≈ 70% at 3 years– ≈ 55% at 5 years
• Amputation: 20-30%• Stump “blow out” (<30%)
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Anatomical/ in situ repair
Straight/ Aorto-bi-femoral/Aorto-bi-iliac
Anatomical/ in situ repair
Straight/ Aorto-bi-femoral/Aorto-bi-iliac
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Graft material optionsArtificial Cryopreserved/
Fresh AllograftsAutologous
• Deep femoral vein• Spiral LSV graft• Lowest infection risk
• Dacron or PTFE• Silver-impregnated• Rifampicin-soaked
• Expensive & needs pre-ordering• Chronic rejection (13%)• Rupture (“cracking”)
Bovine pericardium
• New for aortic grafts• Minimal experience
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O’Connor et al, J Vasc Surg. 2006
Meta-analysis of 37 MEDLINE reports since 1985
Outcomes Extra-anatomicrepair (n=459)
Rifampicin-bonded (n=96)
Cryo-preserved(n=616)
Autogenous vein(n=219)
Amputation 0.08* 0 0.03 0.08
Conduit failure 0.25* 0.02 0.09* 0.17
Re-infection 0.06* 0.07 0.03 0.01*
Early mortality 0.18* 0.07* 0.14 0.10
Late mortality 0.24 0.16 0.14 0.14
All outcomescombined
0.16*§¥ 0.17* 0.09§ 0.10¥
*, §, ¥ denote P < 0.05
Clinical studies involving prosthetic aortic graft infection/mycotic aortic aneurysm
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Survivors (26/33 patients): PET SUVmax <3.8, CRP normal, 25 standard Abx protocol
0
20
40
60
80
100
0 10 20 30 40 50 60
Past 5-year experience with biological conduits for aortic graft infection at GSTT
23 abdominal grafts;
10 thoracic or thoraco-aortic
grafts
In situ repair: 16 autol. vein;
16 bovine;1 cadaveric
Mean op. time 8-9h.
↓1.5h if no DV harvest (i.e. bovine)
No conduit failure, new
infection, amputation;1 DVT 7 wks
Months
Surv
ival
%
Updated from Gradinariu G et al, EVS Meeting, Madrid, 2018
2 deaths (unrelated)
5 deaths (all fistulae initially)
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Courtesy of M Sallam
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Autologous - Spiral LSV graft
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Neo-aorto-iliac system (Bovine & composite grafts)
Courtesy of M Sallam
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Source: wiki
Endovascular aortic repair (EVAR)/Stent grafts
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Aortic Graft Infection Diagnosis: A case Definition by theManagement of Aortic Graft Infection Collaboration (MAGIC)
OTA Lyons et al, European Journal of Vasc & Endovasc Surg 2016: 52, 758-763
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Staph. aureus,20%
Salmonella, 12%
Strep., 11%
Misc., 19%
Salmonella
Non-Salmonella
Salmonella:• 90% 5-year survival
Non-salmonella:• 5-year survival 41%• 50% deaths infection-related
• 16 centers/8 European countries• 123 mycotic aortic aneurysms/EVAR• Blood cultures positive 62%
2014; 130:2136-2142
Culture -ve
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Stented Mycotic Aortic AneurysmsSalmonella enteritidis Staph. aureus
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Biofilm
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Medical management
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Medical management
• Monthly multidisciplinary meeting: surgeons, ID/micro, imaging, pharmacy, nurse specialists
• Monthly Vascular-ID clinic• OPAT service essential• What’s the aim? cure versus suppression?
– Partial vs. complete explanation– Type of repair (in situ/extra-anatomical/stent)– Organisms involved (chronicity, biofilm)– 2 stage planned?: (i) ‘bridging’ stent ⇢ (ii) open repair
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• No case definition• IIa/IIb recommendations (conflicting)• Level C evidence (consensus)
2016
AORTIC GRAFT INFECTION
Extensive peri-graft infection or MRSA, or Pseud,
or MDR orgs?
6/52 IV Abx then4-6/12 PO Abx
Observe off Abx
Lifelong Abx
In situ reconstruction
Graft excision with extra-anatomic
repair
Extensive peri-graft infection or MRSA, or Pseud
or MDR orgs?
Control bleeding/sepsis
YesNo
YesNo
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Situation Duration
Complete removal of infected prosthesis 6 weeks IV + 6 weeks PO
Partial removal of infected prosthesis 6 weeks IV + PO for life
EVAR deployed in infected field e.g. fistula or existing infected graft 6 weeks IV + PO for life
EVAR deployed for mycotic aneurysm6 weeks IV + ≥12 months POStop if Salmonella +ve or BC –ve?(& PET-CT negative & CRP normal)
How long to treat?
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What agents initially?
EMPIRIC TREATMENT
ceftriaxone + metronidazole + vancomycin*
SPECIAL SITUATIONS
Severe sepsis/ unstable Add gentamicin
Enteric/oesophageal fistula Add fluconazole
Pen allergy or MRSA colonised vancomycin + gentamicin + metronidazole
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Total OPAT Episodes = 881
Total OPAT Days = 17544
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OPAT: aortic graft infection target organisms (38 cases)
Empiric, 9
E. coli, 6
CNS, 5MSSA, 4
Pneumococcus, 2
Mixed bowel, 7
Mixed other, 3 Misc, 2
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GSTT OPAT for Vascular Graft Infections
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Outcome: 38 aortic graft infection-OPAT patients
6/52 IV + 6/52 PO50%6/52 IV + LT PO
39%
Other11%
2 deaths(11%)
2 deaths(50%)
5 deaths(33%)
Complications = 7 cases (14%)• Line-related = 2• Medication = 5
Re-admissions = 16 cases (32%)• Emergency = 12• 16.6% s
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The panel addressed the following clinical questions:(I) What preoperative evaluation and intraoperative testing
should be performed to diagnose PJI and what is the de!ni-tion of PJI?(II) What different surgical strategies should be considered
for treatment of a patient with PJI?(III) What is the medical treatment for a patient with PJI
following debridement and retention of the prosthesis?(IV) What is the medical treatment for a patient with PJI
following resection arthroplasty with or without plannedstaged reimplantation?(V) What is the medical treatment for a patient with PJI
following 1-stage exchange?(VI) What is the medical treatment for a patient with PJI
following amputation?
PRACTICE GUIDELINES
“Practice guidelines are systematically developed statements toassist practitioners and patients in making decisions aboutappropriate health care for speci!c clinical circumstances” [12].Attributes of good guidelines include validity, reliability, repro-ducibility, clinical applicability, clinical "exibility, clarity, multi-disciplinary process, review of evidence, and documentation [12].
METHODOLOGY
Panel CompositionA panel of infectious disease specialists and an orthopedist,drawn from North America and Europe, who are experts inPJI was convened. The panelists had both clinical and labora-tory experience with PJI.
Literature Review and AnalysisTwo members of the panel (D. R. O., E. F. B.) initially re-viewed the existing literature. The literature search, which in-cluded the MEDLINE database between 1966 and 2011,Cochrane library database, MD Consult, Up to Date, and theNational Guidelines Clearinghouse, was performed on multi-ple occasions, the last being in April 2011 using multiplesearch terms such as “joint prosthesis” and “PJI.” Hand search-ing of bibliographies of identi!ed articles was also undertaken.
Process OverviewIn evaluating the evidence regarding the management of PJI,the panel followed a process used in the development of otherInfectious Diseases Society of America (IDSA) guidelines. Theprocess included a systematic weighting of the quality of theevidence and the grade of recommendation (Table 1) [5]. Rec-ommendations for the medical management of PJI were
Table 3. Common Antimicrobials Used for Chronic Oral Antimicrobial Suppression (B-III Unless Otherwise Stated in Text)a,b
Microorganism Preferred Treatment Alternative Treatment
Staphylococci, oxacillin-susceptible Cephalexin 500 mg PO tid or qidorCefadroxil 500 mg PO bid
Dicloxacillin 500 mg PO tid or qidClindamycin 300 mg PO qidAmoxicillin-clavulanate 500 mg PO tid
Staphylococci, oxacillin-resistant Cotrimoxazole 1 DS tab PO bidMinocycline or doxycycline100 mg PO bid
!-hemolytic streptococci Penicillin V 500 mg PO bid to qidorAmoxicillin 500 mg PO tid
Cephalexin 500 mg PO tid or qid
Enterococcus spp, penicillin susceptible Penicillin V 500 mg PO bid to qidorAmoxicillin 500 mg PO tid
Pseudomonas aeruginosa Ciprofloxacin 250–500 mg PO bidEnterobacteriaceae Cotrimoxazole 1 DS tab PO bid !-lactam oral therapy based on in vitro
susceptibilitiesPropionibacterium spp Penicillin V 500 mg PO bid to qid
orAmoxicillin 500 mg PO tid
Cephalexin 500 mg PO tid or qid
Minocycline or doxycycline 100 mg PObid
Abbreviations: bid, twice daily; DS, double strength; PO, per oral; qid, 4 times daily; tid, 3 times daily.a Antimicrobial dosage needs to be adjusted based on patients’ renal and hepatic function. Antimicrobials should be chosen based on in vitro susceptibility aswell as patient drug allergies, intolerances, and potential drug interactions or contraindications to a specific antimicrobial.b Clinical and laboratory monitoring for efficacy and safety should occur based on the clinical judgment of the clinician caring for the patient. The possibility ofprolonged QTc interval and tendinopathy should be discussed and monitored when using fluoroquinolones. The possibility of Clostridium difficile colitis shouldalso be discussed when using any antimicrobial.
10 • CID 2013:56 (1 January) • Osmon et al
I D S A G U I D E L I N E S
Diagnosis and Management of Prosthetic JointInfection: Clinical Practice Guidelines by theInfectious Diseases Society of Americaa
Douglas R. Osmon,1 Elie F. Berbari,1 Anthony R. Berendt,2 Daniel Lew,3 Werner Zimmerli,4 James M. Steckelberg,1
Nalini Rao,5,6 Arlen Hanssen,7 and Walter R. Wilson1
1Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota; 2Bone Infection Unit, Nuf!eld Orthopaedic Centre, OxfordUniversity Hospitals NHS Trust, United Kingdom; 3Division of Infectious Diseases, Department of Internal Medicine, University of Geneva Hospitals,4Basel University Medical Clinic, Liestal, Switzerland; 5Division of Infectious Diseases, Department of Medicine, and 6Department of OrthopaedicSurgery, University of Pittsburgh School of Medicine, Pennsylvania, and 7Department of Orthopedics, Mayo Clinic College of Medicine,Rochester, Minnesota
These guidelines are intended for use by infectious disease specialists, orthopedists, and other healthcareprofessionals who care for patients with prosthetic joint infection (PJI). They include evidence-based andopinion-based recommendations for the diagnosis and management of patients with PJI treated withdebridement and retention of the prosthesis, resection arthroplasty with or without subsequent stagedreimplantation, 1-stage reimplantation, and amputation.
Keywords. prosthetic joint infection; PJI; surgical intervention; antimicrobial.
EXECUTIVE SUMMARY
BackgroundJoint replacement is a highly effective intervention
that signi!cantly improves patients’ quality of life, pro-viding symptom relief, restoration of joint function,improved mobility, and independence. Prosthetic jointinfection (PJI) remains one of the most serious com-plications of prosthetic joint implantation. The man-agement of PJI almost always necessitates the need for
surgical intervention and prolonged courses of intrave-nous or oral antimicrobial therapy [1–4]. Despite asigni!cant amount of basic and clinical research inthis !eld, many questions pertaining to the de!nitionof infection as well as diagnosis and management ofthese infections remain unanswered. The focus ofthese guidelines is to provide a consensus statementthat addresses the diagnosis and the medical and sur-gical treatment of infections involving a prostheticjoint. In many situations, the panel has made recom-mendations based on expert opinion, realizing that theamount of data to support a speci!c recommendationis limited and that there are diverse practice patternswhich seem to be equally effective for a given clinicalproblem.
An essential component of the care of patients withPJI is strong collaboration between all involved medicaland surgical specialists (eg, orthopedic surgeons, plasticsurgeons, infectious disease specialists, internists). It isanticipated that consideration of these guidelines mayhelp reduce morbidity, mortality, and the costs associat-ed with PJI. The panel realizes that not all medicalinstitutions will have the necessary resources to
Received 3 September 2012; accepted 5 September 2012.aIt is important to realize that guidelines cannot always account for individual
variation among patients. They are not intended to supplant physician judgmentwith respect to particular patients or special clinical situations. IDSA considersadherence to these guidelines to be voluntary, with the ultimate determinationregarding their application to be made by the physician in light of each patient’sindividual circumstances.
Correspondence: Douglas R. Osmon, Division of Infectious Diseases, Depart-ment of Internal Medicine, Mayo Clinic College of Medicine, 200 First St SW,Marian Hall 5, Rochester, MN 55905 ([email protected]).
Clinical Infectious Diseases 2013;56(1):e1–25© The Author 2012. Published by Oxford University Press on behalf of the InfectiousDiseases Society of America. All rights reserved. For Permissions, please e-mail:[email protected]: 10.1093/cid/cis803
Diagnosis and Management of Prosthetic Joint Infection • CID 2013:56 (1 January) • 1
Clinical Infectious Diseases Advance Access published December 6, 2012
CID 2013
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GSTT aortic graft infection management flowchart
Mycotic aneurysm
Stop Abx after 1yr if Salmonella OR culture –ve AND PET/CRP normal Lifelong
Abx
Staph. aureus or if unstable/ progression?
Endovascular repair (stent) &IV Abx (BC x2)
Explantation of infected graft & in
situ repair with vein, bovine patch or
composite system
6/52 IV + 6/52 PO Abx.Stop Abx after if PET &
CRP satisfactory
Optimise condition('bridging’ stent)?
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GSTT aortic graft infection management flowchart
Infected graft
Major bleeding
risk?Severe sepsis?
Stable?
CT-guided biopsy? & PET
Endovascular repair (stent) &IV Abx (BC x2)
Explantation of infected graft & in
situ repair with vein, bovine patch or
composite system
6/52 IV + 6/52 PO Abx.Stop Abx after if PET &
CRP satisfactory
Lifelong Abx
Residual infected
graft?
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GSTT aortic graft infection management flowchart
Mycotic aneurysm Infected graft
Stop Abx after 1yr if Salmonella OR culture –ve AND PET/CRP normal Lifelong
Abx6/52 IV + 6/52 PO Abx.Stop Abx after if PET &
CRP satisfactory
Major bleeding
risk?Severe sepsis?
Stable?
Staph. aureus or if unstable/ progression?
CT-guided biopsy? & PET
Residual infected
graft?
Endovascular repair (stent) &IV Abx (BC x2)
Explantation of infected graft & in
situ repair with vein, bovine patch or
composite system
Optimise condition('bridging’ stent)?
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Summary & Conclusions
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Conclusions§ Evidence poor, no guidelines, management/outcomes variable§ Small case numbers and a registry needed to track quality§ The multidisciplinary team is essential§ Research
- Diagnostics: sonication, molecular assays- Imaging: PET CT, novel techniques- Antimicrobials: optimum agents, novel therapies, IV vs. oral treatment
and minimum duration- Surgery: graft material, surgical technique
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Novel imaging
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Conclusions§ Evidence poor, no guidelines, management/outcomes variable§ Small case numbers and a registry needed to track quality§ The multidisciplinary team is essential§ Research
- Diagnostics: sonication, molecular assays- Imaging: PET CT, novel techniques- Antimicrobials: optimum agents, novel therapies, IV vs. oral treatment
and minimum duration- Surgery: graft material, surgical technique
§ Similar situation for prosthetic joint infection 20 years ago –now widely accepted evidence-based guidelines
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Acknowledgements
Dr Stephanie ThomasProf Mo BaguneidDr Jonathan SandoeProf S. Homer-VanniasinkamDr Nick FosterDr Abid HusseinDr Tara BarwickDr Katsanos KonstantinosMr Oliver Lyons
Dr Vincenzo AbbateDr Michelle MaProf Phil BlowerProf Bob HiderMs Amita PatelMr Oliver Lyons
Dr. Carolyn HemsleyElizabeth O’DonnellRajeni ThangarajahDr Tadhg SullivanHasinaa PatelMiss Rachel BellMr Morad SallamMr Oliver Lyons
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Micro lab SOP for prosthetic aortic grafts
1) Cut graft in half (N.B. between steel wires)
5) Half of graft for -20°C storage/ sonication
2) Swab both luminal and external surfaces
3) Put piece of graft into Ballotini bead vial and vortex
4) Put remainder in cold room e.g. for 16S PCR if culture neg.
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Sonication
Standard culture 61% vs sonicated 78% (p<0.001)Trampuz et al, NEJM 2007
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MAGIC database
• Management of Aortic Graft Infection Collaboration• Secure, web-entry database hosted by GSTT BRC• Supported by Vascular Society of GB & Ireland• ‘Service evaluation’ (NRES): evaluate the range of diagnostic & therapeutic
approaches• Create useful tool for routine clinical case management• Develop a national registry• Identify key research questions
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http://www.gsttbrc.com/MAGIC
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L4/5 discitis
1. L2–S1 post. spinal instrumented fusion
2. L4/5 decompression3. Debridement of L4/5
spondylodiscitis4. L2 vertebroplasty
Pre-op. Post-op.
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Journal of Clinical Microbiology 2013, 51: 2797–2799
Ann Vasc Surg. 2016
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Silickas et al, 2016 GSTT AGI symposium
45/48 GSTT patients since 2001 met the diagnostic criteria, having scored ≥ 1 major criteria and ≥ 1 from another category. Of the 3 patients that did not meet the criteria, one received palliative care and not investigated, there were incomplete medical records for the second and the third scored 3 minor criteria from 3 different categories but no major.