Evaluation of the anti-infectious properties of polyester vascular prostheses functionalised with cyclodextrin

Abstract

Synthetic vascular graft infection (SVGI) remains associated with high morbidity-mortality rates. Newly developed polyester vascular prostheses (PVP) functionalised with cyclodextrin (PVP-CD) allowed sustained-drug-eluting of several antibiotics. This study aimed to evaluate the efficacy of PVP-CD loaded with antibiotics against bacteria that are commonly responsible for SVGI in current practice. Samples of PVP-CD loaded with antibiotics and uncoated-PVP were tested in-vitro for their ability to limit bacterial adhesion and prevent bacterial proliferation over time. Their anti-infectious properties were further evaluated in-vivo in a mouse model of SVGI. Both Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis, MRSA) and Gram-negative (Escherichia coli, En. cloacae and Pseudomonas aeruginosa) bacteria were tested. PVP-CD loaded with rifampin showed significant bacterial adhesion reduction and growth inhibition against Gram-positive bacteria. Similar results were obtained against Gram-negative bacteria with PVP-CD loaded with ciprofloxacin. In the mouse model, Gram-positive and Gram-negative bacterial proliferations were significantly prevented by PVP-CD loaded with rifampin or with ciprofloxacin respectively. A decrease in macroscopic infections correlated with the bacterial proliferation rates depicted on the samples (Spearman's rho=0.61; P<0.0001). We have demonstrated the efficacy of PVP-CD loaded with appropriate antibiotics both in-vitro and in-vivo against six of the most common bacteria involved in human SVGI.