In vitro Evidence of Improved Antimicrobial Efficacy of Silver and Triclosan Containing Vascular Grafts Compared with Rifampicin Soaked Grafts

Abstract

WHAT THIS PAPER ADDS Thanks to efficient bactericidal activity against Gram positive and negative bacteria as well as yeasts, this study provides in vitro evidence in favour of a vascular graft containing silver and triclosan over a rifampicin soaked graft. The study confirms that rifampicin soaking exposes patients to the risk of hosting rifampicin resistant bacteria compromising the future efficacy of rifampicin. Objectives: The aim was to compare the antimicrobial efficacy of four different grafts: a standard graft (Intergard, IG), an IG graft soaked in rifampicin (IGrif), a silver impregnated graft (Intergard Silver, IGS), and a silver þ triclosan impregnated graft (Intergard Synergy, IGSy). Methods: This was a seven day in vitro study. The IG, IGrif, IGS, and IGSy grafts were each contaminated separately with the following microorganisms: Staphylococcus epidermidis, Methicillin resistant Staphylococcus aureus (MRSA), Escherichia coli, and Candida albicans from both clinical and American Type Culture Collection (ATCC) origins. The in vitro antimicrobial efficacy was evaluated by time to kill assays at T0, T24h, T48h, T72h, and T168h. Bactericidal activity was defined as >3 log 10 reduction factor (logRF). Additionally, Rifampicin, triclosan and silver resistance development were screened. Results: As anticipated for the non-antimicrobial IG, all microorganism strains proliferated. The IGSy and the IGS showed a seven day bactericidal efficacy (>3 logRF) for all tested microorganisms. This efficacy was confirmed at all time points for IGSy only, demonstrating faster bactericidal efficacy than IGS. The IGrif demonstrated a seven day bactericidal efficacy against the ATCC MRSA only, while showing no activity against C. albicans and ATCC E. coli. Regarding ATCC S. epidermidis, clinical MRSA and clinical E. coli, IGrif, although bactericidal at earlier time points, lost its antimicrobial efficacy at seven days leading to the emergence of rifampicin resistant mutants in four of six, two of six, and two of six assays, respectively. Mutant strains were also detected in ATCC MRSA in one of six assays. No triclosan or silver resistance has emerged at T7days. Conclusion: For all microorganisms tested, the Synergy graft combining silver with triclosan demonstrated a more sustainable and efficient seven day antimicrobial activity than the rifampicin soaked graft. The emergence of rifampicin resistant mutants suggests preference for a Synergy graft over a graft soaked in rifampicin, to prevent or treat an infection when a biological solution is not feasible.

Management of neurosurgical implant-associated infections

“…However, the risk of emergence of antimicrobial resistance by using local antibiotics is of concern, particularly for rifampin, as resistance may develop rapidly as a consequence of point mutation. This risk has been observed in rifampin-soaked vascular grafts in vitro [66]. Rifampin is the only biofilm-active antibiotic against staphylococci and development of resistance means that eradication of biofilm infection is impossible.…”

Efficacy of antiseptic impregnation of aortic endografts with rifampicin compared to silver against in vitro contamination with four bacteria that frequently cause vascular graft infections

“…Both the concentration (12 mg/mL) and the flushing time (15 minutes) used in our experimental setup were based on numerous publications with concentrations between 1 and 60 mg and 15 and 30 minutes. All studies had in common that gelatin-coated polyester grafts were used, 4 , 5 , 6 , 7 , 9 , 16 , 19 , 20 because gelatin has been shown to offer the best antibiotic binding properties. 19 Commercially available EG are either made of polyester, as used in this study, or of polytetrafluoroethylene without gelatin pretreatment.…”

“…The lack of gelatin impregnation might explain why we only detected bacteriostatic activity, although bactericidal activity of RIF-soaked gelatin-treated polyester grafts had previously been demonstrated. 9 Therefore, it would theoretically be interesting to repeat the experiment with an EG generation made of gelatin-treated polyester to support the clinical use of RIF treatments of EG. However, we are not aware that such a product is available or planned by any manufacturer.…”

“…Flushing an EG with RIF in cases of an expected increased risk of EGI (eg, systemic infection or bacteremia of nonaortic/vascular origin and nonpostponable aneurysm repair) or known infected aortic pathologies (eg, primary or secondary aortobronchial/aortoesophageal/aortoenteric fistula, mycotic aneurysm) is used in our department for bridging to open surgery or in palliative setting, although the antibacterial effectiveness of RIF impregnation has not yet been proven for EG. The known weak activity against gram-negative strains such as Escherichia coli and Pseudomonas species, methicillin-resistant Staphylococcus aureus (MRSA) and fungi, 5 , 7 , 8 as well as possible development of resistance 8 , 9 limits the use of RIF in most polymicrobially caused vascular graft infections. 6 , 10 …”

“…Silver as an antimicrobial agent has several advantages over RIF, including its wide antimicrobial activity and lack of resistance development. 9 , 11 The efficacy of silver acetate, 12 , 13 , 14 metallic silver, 15 and silver in combination with triclosan 9 , 16 has been proven in multiple clinical and experimental studies.…”