Vascular Graft Infection: Do we

need antimicrobial grafts?

Suat Nail Ömeroğlu

Cardiovascular Surgeon / İ.Ü. Cerrahpaşa Faculty of Medicine,

Turkey

Preventing surgical site infections (SSIs) became a high

priority.

SSIs are the third most common type of health care –

associated infection.

SSIs are associated with

longer postoperative hospital stays,

additional surgical procedures,

admission to intensive care units,

additional medical therapy.

Economic impact of SSIs is significant. In the US, the Center for

Disease Control estimates that hospital costs double for each

patient with a SSI, and the overall costs associated with SSIs are

approximately $10 billion

RD Scott. The Direct Medical Costs of Healthcare-Associated Infections in U.S. Hospitals and the Benefits of

Prevention. Division of Healthcare Quality Promotion National Center for Preparedness, Detection, and Control of

Infectious Diseases Coordinating Center for Infectious Diseases Centers for Disease Control and Prevention,

Atlanta (GA) (2009)

Frequency of SSI

• SSI risk (mean SSI rate 2.48%):

– Carotid artery reconstruction (pooled mean SSI rate: 0.14%)

– Abdominal aorta surgery (pooled mean SSI rate: 1.08%)

– Arterial reconstruction of the lower extremities (pooled mean SSI rate:

3.32%)

Vascular Graft Infection

• Incidence of vascular graft infection range from 0.5% to 6%.

• Morbidity and mortality associated with prosthetic graft infection is high.

– For peripheral vascular prostheses, studies have reported morbidity

rates as high as 41%, with most cases resulting in amputation, and an

attributable mortality of 17%.

– For aortic vascular grafts, the reported mortality rates have ranged from

24% to 75%, with a 5-year survival rate <50%.

Seeger JM: Management of patients with prosthetic vascular graft infections. Am Surg 66:166-177, 2000

Oderich GS, Panneton GM: Aortic graft infections: what have we learnt during the last decades? Acta Cir Belg 102:7-13, 2002

Complications of Prosthetic Graft Infection

• Anastomotic disruption with massive hemorrhage

• Pseudoaneurysm formation

• Graft thrombosis

• Limb loss

• High perioperative and late mortality

Prosthetic Graft Infection

Prosthetic graft infection starts with contamination of the graft and formation

of biofilms. Biofilms result from microbial adhesion to surfaces in moist

environment with sufficient provision of water and nutrients. If the attached

organisms are not immediately separated from the surface or inactivated, they

will start colonizing the surface permanently. Once colonization begins, the

biofilm will grow by a combination of cell division and by genesis of a matrix

of excreted extracellular polymeric substance.

Treatment of infected vascular grafts

• Best treatment remains controversial.

• Early and complete removal of the infected graft, with replacement using

an in situ autologous vein or an extra-anatomic prosthetic bypass.

• Conservative treatment is rarely successful and is used only in high-risk

patients and limited infection.

• The most pre-eminent strategy is primary prevention of vascular graft

infection.

Prevention of Graft Infection

– Preoperative precautions: have the patient shower or scrub with an

antibacterial soap.

– Reduce preoperative stay to minimize the development of skin flora

resistant to commonly used antibiotics.

– Consider any patient attending surgery as being at risk of infection.

– Operative guidelines and aseptic conditions during the operation

– Shorten surgery time,

– Graft protection with muscle flap and multiple layer suture.

– Associated local measures capable of protecting the graft and the

surrounding tissue (Rifampicin soaking, etc.).

Prevention of Graft Infection

• Graft infections still occur.

– There is an increasing prevalence of antibiotic- resistant micro-

organisms, such as methicillin-resistant Staphlococcus Aureus (MRSA)

– Greater than 90% of patients have known risk factors for the

development of graft infection

Efficacy of antibiotic prophylaxis

• 10 RCTs on systemic antibiotics versus placebo demonstrated

a consistent benefit in reduction of wound infection in 1297

patients.

– 6 of 10 RCTs included a case-mix of patients with both prosthetic and

vein grafts. The prophylactic effect of antibiotics is not significant for

prosthetic grafts. It is only statistically significant with vein grafts.

– This meta-analysis mainly investigated β-lactam antibiotics.

Antimicrobial Vascular Grafts

• Antimicrobial compounds need to fulfill a number of distinct requirements:

– Toxicologically safe

– No or limited allergic potency

– Low rate of resorption

– Should not induce bacterial resistance

– Antimicrobially active

Antimicrobial Vascular Grafts

Antibiotic-Bonded Grafts Antiseptic-Impregnated/Coated Grafts

- Vancomycin - Octenidine-dihydrochloride

- Levofloxacin - Polihexanide

- Tobramycin - Triclosan

- Minocycline - Povidone-iodine

- Linezolid - Chitosan

- Levofloxacin-rifampicin - Silver

- Daptomycin-rifampicin

Antimicrobial Silver Grafts

• The first silver-acetate-coated graft (InterGard Silver; Intervascular,

Datascope, Inc, La Ciotat, France) was introduced 13 years ago. It was

designed for routine use in vascular bypass procedures.

• In 2006 another silver-coated device, the B. Braun Silver Graft became

available (B. Braun, Inc, Melsungen, Germany).

• The effectiveness of silver-coated grafts has been shown in-

vitro.

• There are good results with this graft in the aorto-iliaco-

femoral position, but in cases of femorodistal grafting the

difference could not be showed.

New Combination of Antiseptic Agents

Combination of two topical antiseptic agents: silver acetate and

triclosan

Triclosan

• Toxicologically safe

• Rapid antimicrobial action

• Leaches rapidly from the graft material

• Metabolized in the liver

• Stable, synthetic, polychlorinated, aromatic hydrocarbon with broad

antimicrobial properties

• Lipophilic and active within a broad pH range (optimum pH, 4-8)

• After exposure it is cleared from the bloodstream in app. 3.8 days.

Triclosan

• Other products that triclosan is used:

– Medicated soap

– Skin antiseptics

– Catheters

– Surgical sutures

– Kitchenware

– Dishwashing liquids

– Dog’s drinking bowls

– Antimicrobial underwear

(A) Silver ions penetrate the bacterial cell wall and bind to the phospholipid layer of the

cytoplasmic membrane. (B) Bind with the bacterial DNA disrupting DNA replication. (C) Impair

the ability of ribosomes to transcribe messenger RNA. (D) Bind to the sulfhydryl group of the

cytochrome b.

(1) Triclosan binds to bacterial enoyl-acyl carrier protein reductase enzyme (ENR). This binding

increases the enzyme’s affinity for nicotinamide adenine dinucleotide (NAD). This results in the

formation of a stable ternary complex of ENR-NAD-triclosan, which is unable to participate in

fatty acid synthesis. Fatty acids are necessary for reproducing and building cell membranes.

Humans do not have an ENR enzyme, and thus are not affected.

Silver collagen and silver triclosan grafts were designed for

inhibiting microbial colonization of the graft during the early

postoperative period only by providing a release of antimicrobial

agents up to 30 days. Whether this is sufficient to prevent

vascular graft infections in unknown.

Unlike many antibiotics, silver and triclosan are not limited to

one target.

This is why silver acetate and triclosan do not produce bacterial

resistance and, to date, there are no known reported cases in the

vascular surgery literature of silver or triclosan producing

bacterial strain resistance.

Silver acetate and Triclosan

• The bactericidal efficacy against MRSA was shown in vitro

studies.

• The efficacy of this graft against other bacteria and the in vivo

efficacy must be investigated.

Conclusion

• Vascular graft infection is one of the most serious complications of vascular

surgery.

• Conservative treatment of prosthetic graft infections is rarely successful

and is used in very limited number of patients.

• The most pre-eminent strategy against this severe complication is primary

prevention.

• We really need antimicrobial grafts!

• We still don’t know the best antimicrobial agents for this

purpose!