In Vitro and In Vivo Effectiveness of an Innovative Silver-Copper Nanoparticle Coating of Catheters To Prevent Methicillin-Resistant Staphylococcus aureus Infection

Abstract

In this study, silver/copper (Ag/Cu)-coated catheters were investigated for their efficacy in preventing methicillin-resistant Staphylococcus aureus (MRSA) infection in vitro and in vivo. Ag and Cu were sputtered (67/33% atomic ratio) on polyurethane catheters by direct-current magnetron sputtering. In vitro, Ag/Cu-coated and uncoated catheters were immersed in phosphatebuffered saline (PBS) or rat plasma and exposed to MRSA ATCC 43300 at 10 4 to 10 8 CFU/ml. In vivo, Ag/Cu-coated and uncoated catheters were placed in the jugular vein of rats. Directly after, MRSA (10 7 CFU/ml) was inoculated in the tail vein. Catheters were removed 48 h later and cultured. In vitro, Ag/Cu-coated catheters preincubated in PBS and exposed to 10 4 to 10 7 CFU/ml prevented the adherence of MRSA (0 to 12% colonization) compared to uncoated catheters (50 to 100% colonization; P < 0.005) and Ag/Cu-coated catheters retained their activity (0 to 20% colonization) when preincubated in rat plasma, whereas colonization of uncoated catheters increased (83 to 100%; P < 0.005). Ag/Cu-coating protection diminished with 10 8 CFU/ml in both PBS and plasma (50 to 100% colonization). In vivo, Ag/Cu-coated catheters reduced the incidence of catheter infection compared to uncoated catheters (57% versus 79%, respectively; P ‫؍‬ 0.16) and bacteremia (31% versus 68%, respectively; P < 0.05). Scanning electron microscopy of explanted catheters suggests that the suboptimal activity of Ag/Cu catheters in vivo was due to the formation of a dense fibrin sheath over their surface. Ag/Cu-coated catheters thus may be able to prevent MRSA infections. Their activity might be improved by limiting plasma protein adsorption on their surfaces. T he use of intravenous catheters (IVCs) in patients is often associated with the development of bloodstream infection (BSI), metastatic abscesses, and infective endocarditis (1, 2), among other infections. These infections contribute to substantial health care-associated morbidity, prolonged hospital stay, and increased costs (3, 4).IVCs become colonized predominantly by microorganisms present on the skin, most often at the time of intravascular insertion (5, 6). IVC-related infections are most commonly caused by staphylococci, including Staphylococcus aureus, and are particularly problematic in the case of methicillin-resistant S. aureus (MRSA) (7-9).Measures have been developed so far to prevent IVC-related infections (4). Priority is given to hygiene, including maximal barrier precautions during IVC insertion such as skin antisepsis by alcohol disinfection (10), hand hygiene, strict aseptic insertion procedures, and sometimes the use of antiseptic-or antibioticimpregnated dressings or catheters (11,12).The use of aseptic procedures helps in preventing insertionrelated IVC infections (4, 13). However, these measures are limited by practical compliance problems (14). A number of clinical trials have demonstrated that the use of antimicrobial-coated catheters reduce the incidence of S. aureus IVC infections and subsequent BSI...

Self-defending additively manufactured bone implants bearing silver and copper nanoparticles

“…Our results concur with previous studies where combining Ag and Cu enhanced the bactericidal activity against MRSA compared to either Ag or Cu. 41,42 The underlying mechanism causing this synergistic effect remains to be elucidated. 43 The sensitivity of bacteria to Cu is generally lower as compared to Ag, 44 as reflected by the MIC-values obtained in this study.…”

Biomedical Applications of Silver Nanoparticles: An Up-to-Date Overview

“…Catheters treated with silver ions represent a feasible strategy for reducing dialysis-related infections in patients undergoing peritoneal catheters; however, the antimicrobial efficiency and obtaining methods of Ag + are different [ 136 ]. Silver/copper-coated catheters were assessed as a promising solution for preventing methicillin-resistant Staphylococcus aureus (MRSA) infections, since their antibacterial activity might be improved by limiting non-specific plasma protein adsorption [ 137 ].…”

Antimicrobial Nanostructured Coatings: A Gas Phase Deposition and Magnetron Sputtering Perspective

“…In human implantable devices (heart valves or dental implants) with antimicrobial coatings, TiO 2 coatings loaded with NP of Ag, Ca and Si have been shown not only to favor osseointegration [34], but also to prevent thrombosis and the occurrence of inflammation through the reduction of biofilm formation [33,34]. In the case of partially implantable devices, such as catheters, the reduction of infection risk has been investigated by coating the catheter surface with Zn-doped CuO NPs to retard the growth of biofilms [35] and reduce the risk of bacterial infection and complications [99]. The coated catheters present promising antibiofilm activity, biocompatibility, and absence of detectable irritation [35].…”