In recent years, despite the rapid development of endovascular treatment, traditional vascular graft surgery is still an important tool in the management of cardiovascular disease, especially for the treatment of peripheral vascular disease is still in an irreplaceable position. Graft infection is a rare complication after vascular transplantation, with a reported incidence of about 1-6%, and the incidence of 1.14% in the last 20 years in our department. Although the incidence of postoperative graft infection is not very high, it can be very harmful, leading to loss of organ function, amputation, and even life-threatening. The mortality rate caused by infection of aortic graft can be 33-58%, while the mortality rate caused by infection of inguinal graft is relatively low, but it can lead to 79% of lower limb amputation. Therefore, how to prevent and control vascular graft infection is one of the important issues we must face.
Microbiology of vascular graft infections
Most of the vascular graft infections are caused by bacterial infections, and a few are caused by fungi, chlamydia, etc. Early studies showed that Staphylococcus aureus accounted for nearly 50% of all infections. Recently, the spectrum of bacteria causing infections has changed significantly, and coagulase-negative Staphylococcus epidermidis has risen to become the main causative agent. With the widespread use of antibiotics, the proportion of methicillin-resistant Staphylococcus aureus (MRSA) infections has also increased significantly, and in 2000, Nasim [4] found that the proportion of MRSA infections had risen to 63% of surgical vascular incisions and graft infections in the UK. Due to the different mechanisms of bacterial destruction, the results caused by infection are different [3]: Staphylococcus aureus and Pseudomonas aeruginosa produce proteases that can destroy collagen and elastic fibers at the anastomotic site, easily causing necrosis of the host vessel wall, leading to serious consequences of anastomotic bleeding and even arterial rupture; while Staphylococcus epidermidis is a normal skin commensal with weaker virulence and invasive ability, the tissue caused by infection Staphylococcus epidermidis can also produce polysaccharide-like biofilms on the graft surface, which help the bacteria evade the phagocytosis of host leukocytes and the killing effect of antibiotics, and allow the microorganisms to adhere to the surface and spaces of the artificial graft, thus causing chronic or latent infection of the graft.
Risk factors for vascular graft infection
I. Patient’s own factors
It is now clear that the chance of graft infection is significantly higher in elderly patients with coexisting diabetes, uremia, jaundice, obesity, steroid medications, or impaired immunity after vascular transplantation. Lower extremity infections, cellulitis, gangrene, and infected ulcers due to lower extremity ischemia are also risk factors for vascular graft infection.
II. Surgical site
Vascular graft infection is significantly associated with superficial infections at adjacent sites and incisional infections. In the inguinal region, the chance of graft infection is significantly higher than in other sites because this area is susceptible to contamination by the adjacent perineal area, and the more skin folds are conducive to bacterial colonization, and the abundant lymphatic vessels are also prone to postoperative lymphatic fluid leakage. Hematoma in the inguinal region after femoral arteriography may also increase the risk of vascular graft infection; therefore, for those who undergo interventional combined with open surgery, a longer interval between procedures may be beneficial in reducing graft infection.
III. Surgery-related factors
In patients with emergency conditions such as ruptured abdominal aortic aneurysm and acute limb ischemia, vascular grafting may increase the chance of graft infection. In addition, multiple surgeries, prolonged surgical time, repeated exploration of incisions and grafts all have an increased risk of graft infection and should be avoided.
Graft type
The type of graft is also an important factor in determining graft infection. Vascular grafts mainly occur in artificial vessels, while autologous veins have a much lower chance of infection due to their intrinsic resistance to infection. The primary event of artificial vascular infection is bacterial adhesion, and the risk of graft infection is influenced by the different composition of the graft material and the ability of bacteria to adhere to the material. Some in vitro tests have shown that bacterial adhesion capacity is 10 to 100 times higher on braided Dacron IVCs than on ePTFE IVCs, but such a dramatic difference has not been found in clinical statistics.
Diagnosis of vascular graft infections
The diagnosis of vascular graft infection is made mainly based on clinical symptoms, microbiological examination and imaging examination.
I. Clinical symptoms
Graft infection can be divided into early infection (<4 months) and late infection (>4 months) according to the time of occurrence after surgery. Early infection often shows symptoms of systemic toxicity (high fever, elevated white blood cell count), redness, swelling and pain in the incision area, drainage of purulent fluid, graft thrombosis, anastomotic bleeding, etc. Late stage infection lacks specific symptoms and is mostly a manifestation of graft complications (pseudoaneurysm, graft enterocutaneous fistula). The leukocyte elevation is not obvious, but the blood sedimentation is often accelerated. When the infection progresses, there are often local manifestations: redness, swelling and pain of the skin on the graft surface, perigraft mass and sinus tract formation.
Laboratory examination
Laboratory tests mostly show non-characteristic inflammatory manifestations: elevated white blood cell count, increased sedimentation, and elevated C-reactive protein (CRP). A positive bacterial culture of the removed graft or its surrounding punctured fluid is direct evidence of graft infection and may also provide a basis for clinical selection of antibiotics. However, infected microorganisms are usually encapsulated in a biofilm consisting of a polysaccharide matrix, and the exudate around the graft usually only shows elevated white blood cells, which makes it difficult to isolate pathogenic bacteria. Culture of blood and other body fluids can also play an auxiliary diagnostic role, but due to the widespread use of antibiotics, these tests are often negative, especially in patients with advanced infections. In addition, the molecular biology method PCR plays an important role in improving the diagnosis of pathogenic bacteria.
III. Imaging tests
Imaging is currently an important method for diagnosing graft infection. Imaging examination can identify the effusion and inflammatory reaction around the graft, and can perform puncture and drainage of the effusion under its guidance to clarify the diagnosis and guide the treatment. The most commonly used diagnostic imaging methods include CT, MRI, ultrasound, sinus tractography and radionuclide scan. However, in cases of suspected early infection, it is difficult to distinguish whether the imaging changes are caused by the surgery itself or secondary to graft infection. MRI is commonly used to assess the degree of graft infection and can better assess the inflammation of soft tissue. It can differentiate perigraft effusion and inflammatory changes from hematoma. Sinus tractography and radioisotope labeled imaging are also helpful in the diagnosis of graft infection. 111In or 67Ga labeled leukocyte scintigraphy, the scan can reach about 90% accuracy in the diagnosis of graft infection, but inflammation in other areas may interfere with the judgment of the image, and the examination time is slightly longer and vulnerable to hepatobiliary excretory function. Recently, it has been reported [5] that PET/CT has unique advantages for the definitive diagnosis of suspected infection, with a positive predictive rate that can reach 88% and a negative predictive value of 96%. Arteriography is of little use in the diagnosis of graft infection, but is useful as a guide in the development of a surgical plan for revascularization.
Prevention of vascular graft infection
Although the incidence of vascular graft infection is low, it can cause serious consequences, and the management is quite tricky and the prognosis is poor.
I. Control of risk factors
First of all, we should pay great attention to the existing risk factors. For patients with diabetes and malnutrition, special emphasis should be placed on preoperative active glycemic control and supportive therapy, and autologous vein should be used as a graft substitute as much as possible.
II. Prophylactic antibiotic use
The use of perioperative prophylactic antibiotics can effectively reduce the chance of postoperative incision and graft infection, which is usually started at the time of induction of anesthesia, and additional applications can be decided intraoperatively according to the length of surgery, and postoperative applications generally do not exceed 24 hours. When there is an infection far from the surgical site, the infection should be controlled as much as possible before surgery in elective surgery, and the postoperative use of antibiotics can be extended to 3-5 days. Stewart [6] summarized and analyzed several experimental studies to show that there is no significant difference in the effectiveness of the type of antibiotics as prophylaxis, whether they are cephalosporin antibiotics, β-lactam antibiotics, or other classes of antibiotics.
Third, proper surgical operation
Graft infection mainly comes from contamination during surgical operation, and direct contamination caused by the lack of strict intraoperative aseptic operation, contamination of adjacent intestinal tubes, and secondary infection caused by hematoma are the main causes. Obviously, correct surgical operation is an important prerequisite for reducing incision and graft infection. Preoperative marking of the saphenous vein can reduce the free skin when obtaining the saphenous vein and decrease the chance of skin necrosis; during intra-abdominal operation, not only should the intra-abdominal organs be retracted to maintain a good surgical view, but also to avoid graft infection by intestinal microorganisms as much as possible; intraoperative careful free ligation of lymphatic vessels and precise hemostasis can prevent lymphatic fluid leakage and hematoma formation. For the prevention of hematoma formation, surgical operation is more important than local drainage, and conventional negative pressure drainage of the inguinal incision cannot effectively prevent lymphatic leakage and incisional infection.
IV. Drug-carrying vascular grafts
Drug-laden vascular grafts have been studied in previous trials for the prevention of infection, but they have not achieved the expected results in clinical practice. Three European randomized clinical studies of Dacron grafts containing rifampicin have shown [7] that drug-laden grafts may have a preventive effect on early incisional and graft infections, but not on graft infections 2 years after surgery, which Earnshaw suggests may be related to the following reasons [8]: it is still not possible to precisely control the amount of drug loading, the concentration and duration of drug release from the grafts, and Moreover, rifampicin acts mainly on Gram-positive bacteria and is not effective against Gram-negative bacteria and MRSA, which cause clinically serious infections.
Treatment of vascular graft infections
The basic principles of treatment of vascular graft infection include the following parts: removal of the infected vascular graft, removal of necrotic and infected tissue, blood flow reconstruction in the distal limb/organ, and anti-infective treatment. However, because the degree and extent of graft infection varies, clinicians should develop individualized treatment plans based on the specific circumstances of vascular graft infection.
I. Removal of infected vascular grafts
Infected vascular grafts can be a source of persistent sepsis and are at risk for rupture, bleeding and pseudoaneurysm formation. Proper treatment of infected grafts should be made intraoperatively according to the site of graft infection, the degree of involvement, the type of pathogenic bacteria and the patient’s systemic condition. For extra-luminal infections not involving the graft, if there is no sepsis, the artificial vessel is patent and the anastomosis is intact, the graft can be treated by local debridement surgery with the graft intact [9], and the exposed graft is covered with a transfer myocutaneous flap with anti-infective ability and good blood flow. For infections confined to the distal end of the aorto-femoral vascular graft, only the infected artificial vessel arm can be removed and partially preserved when the proximal aorta and the anastomosis are confirmed to be free of infection. Since Pseudomonas aeruginosa and MRSA infection can cause serious consequences such as anastomotic hemorrhage, when their infection is confirmed, the infected graft should be removed as completely as possible, while in the case of coagulase-negative Staphylococcus epidermidis infection, graft preservation surgery is feasible when possible.
Removal of necrotic and infected tissues
The arterial wall and the tissues surrounding the artificial vessel should be cleared to normal tissue to create a clean surface for tissue repair. However, it is often difficult to completely remove necrotic tissue to meet this requirement, especially in the management of aortic graft infections. Surgeons often do not want to remove more aortic stumps and attempt to preserve the anastomosis of the subrenal stump, thus leaving behind an infected aortic wall with serious consequences. When dealing with aortic stumps, the risk of rupture can be reduced by using an active sterile tissue cover.
III. Reconstruction of blood flow in the distal limb/organ
After removal of the infected vascular graft, blood flow reconstruction to the distal limb/organ is generally required. Only in the rare cases where collateral circulation has been adequately established or where the original vascular graft was done only to relieve intermittent claudication symptoms, revascularization may not be performed. To avoid reinfection of the graft, the traditional revascularization protocol is through an extra-anatomic route and the procedure can be done in one stage or in stages. Traditional infected graft removal combined with extra-anatomic bypass surgery can reduce the mortality rate of infection to 13%-30%, the amputation rate to 18%-24%, and the 5-year survival rate to about 50% [10], but the extra-anatomic route is extensive, traumatic, and prolonged, and there are concerns about rupture of the aortic stump. Therefore, there have been many attempts to perform in situ revascularization or retroperitoneal bypass, and Daenens [11] replaced 49 infected aortic grafts with autologous femoral veins in situ with a 5-year survival rate of 60% and a patency rate of 91%, with no graft reinfection or aneurysmal dilatation noted.
The graft materials available for revascularization are: artificial vessels, autologous vessels, deep cryogenic frozen allografts and drug-carrying vascular grafts. Among them, autologous vessels are the best choice, but in most cases, there are no suitable autologous vessels available. In order to solve the problem of graft reinfection during in situ reconstruction, attempts have been made in recent years to apply deep cryopreserved allografts and drug-laden vascular grafts with more satisfactory results. The early mortality of reconstruction was low, and complications such as reinfection were not significantly different.
However, due to the small number of cases of graft infection, some of the new attempts are case reports and there are no large randomized group controlled studies, and the type of reconstruction protocol and graft material used currently depends largely on the surgeon’s proficiency and the patient’s own needs.
Anti-infective therapy reduces the chance of sepsis and reinfection, is an extremely important complement to surgery, and is the only option for treatment of graft infection when the patient is not a candidate for surgery. When bacterial cultures are positive, anti-infective therapy is based on the results of drug sensitivity tests and is often recommended for at least 6 weeks of intravenous administration followed by 6 months of oral antibiotics, with treatment durations of up to 1 year also reported in the literature. There is no consensus on which antibiotic is more appropriate for empirical treatment, and considering that nosocomial infections account for the majority of infections, the British Antibiotic Chemotherapy Association recommends cephalosporins and metronidazole as empirical treatment for early infections [13]. For patients with MRSA infection, glycopeptide antibiotics (e.g., vancomycin, teicoplanin, etc.) should be used. As for patients with advanced infections, except for critically ill patients, it is recommended to withhold anti-infective therapy until the causative organism is clearly identified.
In conclusion, although the incidence of vascular graft infection is not high, it can cause serious consequences, so we should pay attention to the prevention of perioperative vascular graft infection, and for vascular grafts that have been infected, we should develop individualized treatment plans according to the specific circumstances of the infection.