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Graft Infection


Introduction

The incidence of infection involving vascular prostheses is relatively low because of routine antibiotic prophylaxis before surgical procedures, refinements in the sterilization and packaging of devices, and careful adherence to aseptic procedural and surgical technique. When infection does occur, detection and definitive therapy of the vascular prosthesis are often delayed, with potentially catastrophic consequences. If it is not recognized or treated promptly, implant failure will occur as a result of sepsis, vessel disruption and hemorrhage, or thrombosis with end-organ ischemia. The clinical manifestations of prosthetic vascular infection vary depending on the anatomic location and the virulence of the pathogen. , , , In general, surgical therapy is always required, often coupled with excision of the prosthesis, because antibiotics alone are insufficient to eradicate an established infectious process. An appropriate treatment plan is influenced by the clinical findings, anatomic location, time since initial implantation, type of graft/device material, extent of infection, virulence of infecting organism, and the patient’s underlying comorbid conditions.

Keys to a successful outcome include accurately identifying the infecting organism and the extent of the graft infection; administration of culture-specific antibiotic therapy; well-planned surgical intervention(s) to preserve, excise, or replace the infected graft; sterilization of the local perigraft tissues; and maintenance of adequate distal organ/tissue perfusion. Improved results have been reported in the past 30 years after both graft excision coupled with extra-anatomic bypass and in situ replacement procedures. Because most patients with late manifestations have a low-virulence graft infection, in situ replacement therapy with autogenous venous conduits, cryopreserved allografts, or antibiotic-impregnated prostheses to replace the infected grafts has evolved to become a preferred treatment strategy. , , ,

Incidence

The reported incidence of infection involving a vascular prosthesis varies from 0.2% to 5% of open operations and is influenced by the implant site, indication for the intervention, underlying disease, and host defense mechanisms ( Table 49.1 ). , , , , Graft infection occurs much less frequently than wound infection, with the incidence of early (<30-day) graft infection being in the range of 1% to 2%. Infection is more likely to involve prosthetic grafts implanted during an emergency procedure, when the prosthesis is anastomosed to the femoral artery or placed in a subcutaneous tunnel. In a Canadian prospective multicenter trial of nonruptured AAA open repair, the incidence of graft infection was 0.2%, similar to that reported after endovascular aneurysm repair (EVAR). , Infection can also develop after deployment of a bare stent, but the incidence appears to be extremely low (<0.1%) ( Box 49.1 ).

TABLE 49.1
Incidence of Prosthetic Graft and Endovascular Device Infection Relative to the Implant Site
Infection Incidence (%)
Graft Implant Site
Descending thoracic aorta/thoracoabdominal 0.5–1.9
Aortoiliac 0.2–1.3
Aortofemoral 0.5–3
Femorofemoral 1.3–3.6
Axillofemoral 5–8
Femoropopliteal 0.9–4.6
Femorotibial 2–3.4
Carotid patch 0.25–0.5
Carotid–subclavian 0.5–1.2
Axillo–axillary 1–4
Endovascular Device
Aortic endograft 0.1–1.2
Peripheral stent <0.1

BOX 49.1
Clinical Classifications of Prosthetic Graft Infections

Time of Appearance After Implantation

  • Early: <4 months

  • Late: >4 months

Relationship to Postoperative Wound Infection (Szilagyi’s Classification)

  • Grade I: cellulitis involving the wound

  • Grade II: infection involving subcutaneous tissue

  • Grade III: infection involving the vascular prosthesis

Extent of Graft Involvement (Bunt’s Classification Modified)

  • Arterial graft infection:

    • P0 graft infection: Infection of a cavitary graft (e.g., aortic arch; abdominal and thoracic aortic interposition; aortoiliac, aortofemoral, iliofemoral graft infections)

    • P1 graft infection: Infection of a graft whose entire anatomic course is noncavitary (e.g., carotid-subclavian, axillo–axillary, axillofemoral, femorofemoral, femoropopliteal/tibial)

    • P2 graft infection: Infection of the extracavitary portion of a graft whose origin is cavitary (e.g., infected groin segment of an aortofemoral or thoracofemoral graft, cervical infection of an aortocarotid graft)

    • P3 graft infection: Infection involving a prosthetic patch angioplasty (e.g., carotid and femoral endarterectomies with prosthetic patch closure)

  • Graft-enteric erosion (GEE)

  • Graft-enteric fistula (GEF)

  • Aortic stump sepsis after excision of an infected aortic graft

Pathogenesis

The presence of a foreign body potentiates the infectivity of bacteria. In 1957, Elek and Conen demonstrated that a single braided silk suture significantly reduces the inoculum of staphylococci required to produce a local infection. The risk of foreign body infection is enhanced in the presence of a larger inoculum, more virulent bacterial strains, depressed host immune function, and invasion of sites more remote from host defenses.

Cellular and Biomolecular Events

The pathogenesis of biomaterial-associated infection involves the following fundamental steps: (1) adhesion of bacteria to graft or stent surfaces; (2) formation of microcolonies within a bacterial biofilm; (3) activation of host defenses (neutrophil chemotaxis, complement activation); and (4) an inflammatory response involving perigraft tissues and the graft-artery anastomoses.

After adherence of bacteria to the biomaterial surface, both graft and bacterial characteristics influence the likelihood of colonization. Bacterial adherence to polyester grafts is 10 to 100 times greater than adherence to polytetrafluoroethylene (PTFE) grafts. Gram-positive bacteria, such as staphylococci, produce an extracellular glycocalyx, or mucin, that promotes adherence to biomaterials in greater numbers than are seen with Gram-negative bacteria. The increased adhesion of staphylococci to biomaterials is due to specific capsular adhesions that mediate the attachment and colonization of microorganisms. The vascular prosthesis and adherent bacteria together stimulate the immune system through inflammatory cytokines. The local inflammatory response after implantation serves to establish connective tissue ingrowth (“incorporation”) to the outer surface of the graft material. This healing process can be impaired by early perigraft seroma or hematoma formation, which increases the risk for bacterial adherence and colonization. The inflammatory response also creates an unfavorable healing environment characterized by local ischemia and an acidic pH that is potentially conducive to bacterial colonization. Local disruption of the fine balance between pro- and anti-inflammatory mediators may lead to excess production of matrix metalloproteinases (MMPs) by tumor necrosis factor-stimulated macrophages. Excessive degradation of secreted extracellular matrix and angiogenic growth factors by MMPs may hinder optimal graft healing by restricting capillary ingrowth, tissue incorporation, and potential luminal endothelialization. Lack of perigraft ingrowth and vascularity also favors greater exposure of the implanted biomaterial to bacteria and sequestration within graft pores/interstices away from activated phagocytic cells. Neutrophil function can also be directly impaired in the presence of biomaterials. Decreased neutrophil opsonic, phagocytic, and bactericidal activity against Staphylococcus aureus has been observed in PTFE tissue cages implanted subcutaneously in guinea pigs.

Clinical Sources of Infection

Exposure of a vascular prosthesis to microorganisms (bacteria or fungi) can result in clinical infection by any of four mechanisms: perioperative contamination via the surgical wound; bacteremic seeding; mechanical erosion into the bowel, genitourinary tract, or through the skin; and involvement in a contiguous infectious process. Underlying impairment of host defenses can further increase the risk for infection.

Perioperative Contamination

Skin and lymph nodes are major reservoirs of bacteria. Biomaterial surfaces can contact microorganisms (1) by a direct route during implantation, (2) through the surgical wound, or (3) by hematogenous or lymphatic sources arising from remote sites of infection. Potential sources of direct graft contamination include breaks in aseptic operative technique and contact with a patient’s endogenous flora harbored within sweat glands, lymph nodes, diseased arterial walls (atherosclerotic plaque or aneurysm thrombus), disrupted lymphatics, and intestinal bag effluents as well as injury to the gastrointestinal or genitourinary tract. Reoperative and urgent/emergent vascular procedures and prolonged operative time also increase the risk of vascular surgical site infections (VSSIs).

If the surgical wound does not develop a fibrin seal or heal promptly after surgery, the underlying vascular prosthesis is susceptible to colonization from any superficial wound complication (cellulitis, dermal necrosis, lymphocele). Wounds with persistent drainage indicate the presence of ischemia or tissue injury that can extend to deeper tissue and involve the prosthesis. Diseased arterial walls and reoperative wounds are an unappreciated source of bacteria, with microbiologic culture recovering pathogenic strains of staphylococci in 10% to 20% of cases. Bacteria can be harbored in scar tissue or lymphoceles of healed wounds and can contact prosthetic grafts undergoing revision or arterial replacement. Culture of explanted graft material from such procedures has isolated microorganisms, typically S. epidermidis , from 50% to 70% of thrombosed grafts and from more than 80% of grafts associated with anastomotic aneurysms.

Bacteremia

Bacterial seeding of the prosthesis via a hematogenous route is an uncommon but important mechanism of graft and stent infection. Experimentally, intravenous infusion of 10 7 colony-forming units of S. aureus administered within days of implantation produces a clinical graft infection in nearly 100% of animals. Thus bacteremia arising from infected intravascular catheters, urinary tract infection, pneumonia, or infected foot wounds increases the risk of graft infection.

Parenteral antibiotic therapy has been shown experimentally to significantly decrease the risk of graft colonization from bacteremia and this is the rationale for both antibiotic prophylaxis and culture-specific antibiotic therapy in patients with a known site of infection. As the prosthesis heals and becomes incorporated into surrounding tissue, susceptibility to bacteremic colonization decreases but vulnerability has been documented more than 1 year after implantation, with infection developing as a result of dental and gastrointestinal diagnostic procedures. Transient bacteremia, in conjunction with altered immune status, may account for some graft infections occurring years after the original operation.

Mechanical Erosion

Erosion of a prosthetic graft through the skin or into the gastrointestinal or genitourinary tract results in a perigraft infection that can spread along the length of the graft. Graft-enteric erosion/graft-enteric fistula (GEE/GEF) can develop as a result of pulsatile movement of an aortic graft against adjacent bowel, most commonly without adequate intervening retroperitoneal soft tissue. Enteric erosion may involve the graft body or anastomotic sites with intact suture lines or pseudoaneurysm formation. A low-grade underlying graft infection has been found in a fraction of cases (confirmed by operative findings and recovery of staphylococcal species) and may provide an additional inflammatory stimulus for bowel adhesion. The reported incidence of GEE/GEF after prosthetic aortic grafting is 0.4% to 2%.

Involvement by a Contiguous Infectious Process

Prosthetic grafts can become colonized as a result of an adjacent infection. The most common clinical scenarios are an aortofemoral graft limb infection associated with diverticulitis and a peripheral graft infection secondary to an infected lymphocele. Frequently the graft segment adjacent to the contiguous bowel or soft tissue infection may be involved.

Impaired Host Defenses

Impaired host defenses from underlying systemic conditions can also predispose patients to prosthetic graft infection. The altered immune function associated with malnutrition, malignancy, lymphoproliferative disorders, autoimmune diseases, chronic renal insufficiency/uremia, advanced liver disease, drug administration (corticosteroids, antineoplastic and immune-modulating agents), and potentially diabetes mellitus may potentiate graft infection with lower numbers of contaminating bacteria.

Bacteriology

Although any microorganism can infect a vascular prosthesis, S. aureus is the most prevalent pathogen and accounts for 25% to 50% of infections, depending on the implant site ( Table 49.2 ). Graft infections with S. epidermidis or Gram-negative bacteria have increased in frequency. This change in the microbiology of graft infection is the result of reporting of both early- and late-appearing graft infections, including aortic graft infections associated with GEE/GEF. Coagulase-negative staphylococci are present in normal skin flora but have the ability to adhere to and colonize biomaterials, where growth occurs within a biofilm on the surface of prostheses. Surgeons have also become aware of microbiologic sampling errors in late infections because of low numbers of bacteria present within the graft surface biofilm and their slow growth. Graft infections associated with negative culture results are caused by S. epidermidis or other coagulase-negative staphylococci and by Candida species. Infection with Gram-negative bacteria such as Escherichia coli and Pseudomonas , Klebsiella , Serratia , and Proteus species can be particularly virulent. The incidence of anastomotic dehiscence and arterial rupture is high because of the ability of the organisms to produce destructive endotoxins (elastase and alkaline protease) that compromise the structural integrity of the vessel wall. Fungal ( Candida and Aspergillus species) and mycobacterial (tuberculous) infections of grafts are rare, and most patients with such infections are either severely immunosuppressed or have an established fungal or opportunistic infection elsewhere.

TABLE 49.2
Bacteriology of Prosthetic Vascular Graft Infections from Collected Series
Microorganism Incidence (%)
Thoracic Aorta Graft-Enteric Erosion/Graft-Enteric Fistula Aortofemoral Femoral/Popliteal/Tibial Carotid
Staphylococcus aureus 32 4 27 28 50
Staphylococcus epidermidis 20 2 26 11 15
Streptococcus spp. 2 9 10 11 3
Pseudomonas spp. 10 3 6 16 6
Coliforms/Gram-negative organisms a 14 49 28 29 9
Other species/Candida 10 15 1 3 5
No growth/no culture 12 18 2 2 12

a Escherichia coli ; Enterococcus, Bacteroides, Klebsiella, Enterobacter, Serratia, Proteus species.

Plasmid-mediated genetic mutations have afforded S. aureus resistance against penicillin, β-lactams, and other antibiotics (aminoglycosides, erythromycin, tetracycline). Nosocomial and community-acquired infections caused by methicillin-resistant S. aureus (MRSA) have rapidly increased in prevalence over the past 15 years. Although estimates in the general population have shown MRSA skin colonization (nares and wounds) in less than 2% of individuals, a much higher prevalence is found in residents of long-term care facilities (23%–49%). A study involving more than 13,000 surgical patients admitted to a tertiary hospital in Switzerland found that the overall incidence of MRSA carriers was 4%, but of those carriers, 64% were newly identified. Previous hospitalization, age greater than 75 years, and recent antibiotic treatment were each prognostic for unsuspected MRSA carriage. The combination of increased prevalence, harboring in high-risk populations, multiple staphylococcal virulence factors, and rapidly evolving antibiotic resistance mechanisms makes emergence of MRSA a daunting medical challenge. British reports have documented MRSA as the most common pathogen involved in vascular wound and graft infections and concluded that it is associated with higher morbidity and mortality rates than infection with other microbes. , At the University of South Florida (USF), the prevalence of MRSA arterial graft infections increased four-fold over a 25 year span (from 11% before 2000 to 49% after 2000), with more than half of early extracavitary graft infections being the result of MRSA. Early mortality, limb loss, and infection recurrence rates have not been appreciably higher for MRSA in the USF experience. However, the future possibility of a higher overall incidence of graft or vascular device infections caused by more prevalent MRSA colonization in the vascular population is concerning.

Prevention Principles

Surgical site infection (SSI) guidelines have recently been updated and a comprehensive review has been generated by the American College of Surgeons and the Surgical Infection Society.

VSSIs can be minimized if the following principles are applied:

  • 1.

    Avoid a prolonged preoperative hospital stay to minimize the development of more resistant hospital-acquired bacterial strains.

  • 2.

    Have patients shower, scrub, or wipe with an alcohol-based soap (e.g., chlorhexidine) for 1 to 3 days before the operation.

  • 3.

    Control remote infections before an elective vascular operation.

  • 4.

    Remove hair from the operative site immediately before the operation with care to avoid skin trauma.

  • 5.

    Protect vascular grafts from contact with exposed skin in the operative field by using iodine-impregnated plastic drapes or antibiotic-soaked towels/sponges.

  • 6.

    Avoid concomitant gastrointestinal procedures during cavitary grafting procedures.

  • 7.

    Use prophylactic antibiotics (30–60 minutes before skin incision) prior to open surgical implantation of a prosthetic graft.

  • 8.

    Longer (>24 hours) duration of periprocedural antibiotics may be considered when two or more patient-related high-risk factors for surgical wound infection are identified, including extremes of age, malnutrition, prolonged hospitalization, remote infections, immunosuppression, recent or “redo” operations, and previous irradiation of the surgical site.

  • 9.

    Measures aimed at controlling MRSA include the use of disposable barriers (gowns, gloves, masks) by all individuals contacting MRSA carriers to reduce direct transmission within hospitals, routine MRSA screening (nares swab) of all admitted patients, and use of nasal mupirocin ointment and repeated chlorhexidine skin cleansing before operations.

  • 10.

    Meticulous attention to sterile technique. Careful handling of tissues, prevention of hematoma formation, and closure of groin incisions in multiple layers to eliminate dead space with lymphatic resection/ligation are imperative to reduce wound complications. Skin reapproximation without tension minimizes the development of dermal ischemia and wound edge necrosis.

Topical Antibiotics

The addition of topical antibiotics (bacitracin or cefazolin) to irrigating solutions allows soaking of grafts before implantation and cleansing of wounds before closure and may contribute to decreased wound infection rates. Randomized clinical trials using rifampin-soaked (1 mg/mL) gelatin-impregnated polyester aortofemoral grafts have reported significantly reduced groin wound infection rates (4.4% without rifampin vs. 2.7% with rifampin), although the rates of subsequent graft infections were similar (0.6% vs. 0.3%). , All graft infections were caused by S. aureus in this study. On the basis of the absence of a longer-term benefit, routine rifampin treatment of polyester grafts for primary aortic reconstruction cannot currently be recommended.

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