New antimicrobial surfaces and intravascular catheters for the prevention of healthcare-associated infections

Abstract

Healthcare-associated infections (HAIs) are an important health issue around the world. The consequences of HAIs incidence include prolonged hospital stays, increased resistance of microorganisms to antimicrobials, higher costs for health systems and for the patients, and an increase in morbidity and mortality. Microbial and fungal contamination and colonization of abiotic surfaces and intravascular catheters (IVCs) are major risk factors that increase the incidence of HAIs. A number of measures aimed at reducing the contamination of abiotic surfaces and catheter colonization have been implemented, such as surface cleaning and disinfection, hand hygiene and the use of sterile barrier precautions. However, such measures have limited efficacy and have failed to eradicate completely HAIs. For this reason, an attractive approach to overcome this issue is to design surfaces and IVCs which exhibit self-disinfecting activity. This thesis focused on these two important causes responsible for the high incidence of HAIs and their prevention. First, the antimicrobial activity of copper-coated surfaces was assessed. To this aim, we used an innovative coating technique, direct current magnetron sputtering (DCMS), to generate flexible copper-sputtered polyester surfaces (Cu-PES). Then, the antimicrobial activity of these surfaces was tested under dark and visible light irradiation conditions against a broad spectrum of antimicrobial resistant (AMR) pathogens. In addition, we investigated the mechanism of the killing process of microbial cells caused by those surfaces. It was shown that flexible Cu-PES have a rapid bactericidal activity (within minutes) under dark conditions against all tested AMR bacteria, which was likely induced by a contact killing process. Then, the activity of Cu-PES was assessed against yeast under dark and visible light irradiation conditions. We showed that the photo-activation of those surfaces led to an acceleration of the fungicidal activity compared to the activity under dark conditions. The faster antifungal effect induced by visible light was due to the semiconductor Cu2O/CuO charge separation. Second, DCMS technology was used to generate copper (Cu)-coated IVCs (first generation of catheters) and silver-copper (Ag/Cu)-coated IVCs (second generation of catheters). The ability of these two generations of coated-IVC to prevent catheter colonization by methicillin-resistant Staphylococcus aureus (MRSA), a major culprit of catheter-related bloodstream infections in hospitalized patients, was assessed both in vitro and in vivo, in a rat model of IVC infection to closely mimic the infection occurring in humans. First generation catheters (Cu-coated) showed a significant efficiency in vitro in preventing catheter colonization by MRSA but were less effective to prevent in vivo infection caused by MRSA. Second generation of catheters, Ag/Cu-coated catheters, completely prevented MRSA infection in vitro. In addition, they reduced the rate infection in vivo. The higher antimicrobial activity was likely due to a synergistic effect between silver and copper. However, even if the infection rate in vivo was reduced, it was not fully prevented. This was explained by the adsorption of plasma proteins onto the catheters, which created a sheath that inhibited catheter-bacterial contact. Overall, these findings suggest that DCMS technology is a suitable strategy to design novel antimicrobial surfaces and coated-IVC for preventing HAIs.