1. Stephanie Thomas Consultant Microbiologist Wythenshawe Hospital Early & Late Onset Vascular Graft Infection Microbiology aspects

2. prosthetic vascular graft infection (PVGI) –incidence 1 – 6 % (infra-inguinal 2-5%, aortofemoral 1-2%, aortic 1%) –relative risk low –clinical consequences catastrophic! –recognized mortality 30-50% (up to 75% with intra-abdominal aortic grafts) –associated morbidity 40-70% (limb amputation rates up to 70% for lower extremity grafts) significant complication of arterial reconstruction

3. risk factors for PVGI –groin incision –wound complications –immunosuppressive therapy –diabetes –cancer –immunologic disorders

4. SzilagyiDefinition of infectionSamsonDefinition of infection Group 1dermis onlyGroup 1no deeper than dermis Group 2extends to subcut tissues, does not invade implant Group 2involves subcut tissue, does not come into contact with graft Group 3arterial implant involvedGroup 3involve body of graft but not anastomosis based on level of: anatomic invasion graft involvement Group 4surrounds exposed anastomosis, no bacteramia/bleeding Group 5involve graft-to-artery anastomosis, associated with septicaemia/bleeding early PVGI classifications

5. last 10 years: re-classification early (acute) onset: < 4 months post operative –present as acute infection late onset: > 4 months post operative –up to 95 months post graft implantation * –insidous onset, systemic signs often missing –aetiology less certain –far more difficult to diagnose more pragmatic approach for diagnosis, predicting microbial aetiology and treatment regimes * Seabrook et al, 1990, J Vasc Surg

6. clinical presentation: early v late time of onsetclinical presentation early-acute (<4 mo) traditional SSI presence of graft exacerbates clinical severity post surgical wound infection wound complications: anastomotic dehiscence, hematoma, seroma, incisional necrosis sepsis (blood cultures!) late (> 4 mo) can be many months/yrs occult/few or no overt sx anastmotic pseudoaneurysm peri-graft exudation with sinus formation graft thrombosis and failure graft-enteric erosion, fistula formation, hemorrhage

7. microbial aetiology: early v late time of onset microbial aetiology?? treatment early- acute (<4 mo) Staphylococcus aureus Streptococci Incision site contamination: E.coli, Klebsiella, Pseudomonas Augmentin Flucloxacillin & Gentamicin late (>4 mo) E.coli, Klebsiella, Bacteroides, Candida Coagulase negative staph (Staph.epidermidis) ??????

8. HPA Surgical Site Infection Surveillance Service (SSISS) National aggregated data on Surgical Site Infections (2004-09) [33 hospitals (voluntary), 7,349 operations ]

9. staphylococcal predilection for implants Bandyk et al Arch Surg (1990) S. epidermidis the infecting organism >60% of aortofemoral graft infections Kaebnick HW et al, Surgery (1987) S. epidermidis isolated from 75% of prostheses revised for anastomotic pseudoaneurysm and 80% of aortofemoral prostheses removed because of infection Macbeth GS et al, J Vasc Surg (1984) S. epidermidis cultured from diseased arterial walls and groin lymph nodes in one third patients undergoing vascular prosthesis implantation

10. late onset infections CoNS: ubiquitous group, low virulence, significant pathogens in biomaterial-related infections exopolysaccharide/ biofilm production (slime) source of infection : contact with prosthetic surface during implantation (c.f.PJI, PVIE) –initial cryptic period –organisms colonise surfaces as bacteria-laden biofilm –protected by host defences glycocalix (slime) –lie dormant for years in biofilm growth mode

11. enlarging infection eventually recognised by the host –chronic inflammatory response adjacent to the graft –autolysis of peri-graft tissue and adjacent arterial wall –perigraft exudate, fluid collection –in time decreases the anastomotic tensile strength of anastomotic graft-artery interface slime producing strain of S.epidermidis colonising fibres of a dacron vascular graft

12. –prophylaxis efficacious BUT does not guarantee graft sterility –implanted prosthesis colonised with low virulence organisms (skin, harboured in diseased arteries, breaks in surgical technique, bacteraemia) persistance – sinus formation - pseudoaneurysm late graft failure

13. outcome by organism Zetrenne E, Bryan M, McIntosh B et al. (2007) –multi centre retrospective study to determine primary mode of therapy and rate of limb salvage for major PVGI –Samson Group 3-5 –correlated grade, microbiology, outcomes –??success of graft salvage determined by infective organism

14. outcomes by group and organism

15. principles of management for PVGI evolved over 40 years –predominantly based on clinical experience –moderate amount of supportive lab evidence –no standardised methodology (sampling or processing) –current methods poorly sensitive –low density organisms, stationary growth mode –disrupt biofilm: sonication techniques, Balotini bead technique look for slime production anti-staphylococcal antibody titres

16. laboratory support –Standard Operating Procedure –standard sample set –national consensus treatment guidelines re. choice & duration ? dependant on site of graft; e.g. aortic v peripheral Intervention: salvage v excision

17. Legout L, D’Elia PV, Sarraz-Bournet B, et al (2012). Med Mal Infect. there is no correlation between the microbiological data and the location or type of vascular infection. thus, the post operative intravenous antibiotherapy should be bactericidal with broad spectrum. after obtaining intra-operative microbiological results, de-escalation therapy must include at least one anti- adherance agent, such as rifampicin in staphylococcal infections.

18. summary: PVGI early onset: –acute presentation –post operative wound infection –microbiology representative –antibiotic choice narrow late onset: –insidious onset –low index of suspicion –microbiology variable –broad spectrum include Gram-negative & anti-biofilm agent concern re changing patterns of resistance