Medical devices such as venous catheters (VCs) and urinary catheters (UCs) are widely used in the hospital setting. However, the implantation of these devices is often accompanied by complications. About 60 to 70% of nosocomial infections (NIs) are linked to biofilms. The main complication is the ability of microorganisms to adhere to surfaces and form biofilms which protect them and help them to persist in the host. Indeed, by crossing the skin barrier, the insertion of VC inevitably allows skin flora or accidental environmental contaminants to access the underlying tissues and cause fatal complications like bloodstream infections (BSIs). In fact, 80,000 central venous catheters—BSIs (CVC-BSIs)—mainly occur in intensive care units (ICUs) with a death rate of 12 to 25%. Similarly, catheter-associated urinary tract infections (CA-UTIs) are the most commonlyhospital-acquired infections (HAIs) worldwide.These infections represent up to 40% of NIs.In this review, we present a summary of biofilm formation steps. We provide an overview of two main and important infections in clinical settings linked to medical devices, namely the catheter-asociated bloodstream infections (CA-BSIs) and catheter-associated urinary tract infections (CA-UTIs), and highlight also the most multidrug resistant bacteria implicated in these infections. Furthermore, we draw attention toseveral useful prevention strategies, and advanced antimicrobial and antifouling approaches developed to reduce bacterial colonization on catheter surfaces and the incidence of the catheter-related infections.

Due to their ability to eliminate antimicrobial resistant (AMR) bacteria and to modulate the immune response, host defence peptides (HDPs) hold great promise for the clinical treatment of bacterial infections. Whereas monotherapy with HDPs is not likely to become an effective first-line treatment, combinations of such peptides with antibiotics can potentially provide a path to future therapies for AMR infections. Therefore, we critically reviewed the recent literature regarding the antibacterial activity of combinations of HDPs and antibiotics against AMR bacteria and the approaches taken in these studies. Of the 86 studies compiled, 56 featured a formal assessment of synergy between agents. Of the combinations assessed, synergistic and additive interactions between HDPs and antibiotics amounted to 84.9% of the records, while indifferent and antagonistic interactions accounted for 15.1%. Penicillin, aminoglycoside, fluoro/quinolone, and glycopeptide antibiotic classes were the most frequently documented as interacting with HDPs, and Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Enterococcus faecium were the most reported bacterial species. Few studies formally evaluated the effects of combinations of HDPs and antibiotics on bacteria, and even fewer assessed such combinations against bacteria within biofilms, in animal models, or in advanced tissue infection models. Despite the biases of the current literature, the studies suggest that effective combinations of HDPs and antibiotics hold promise for the future treatment of infections caused by AMR bacteria.

The antibiotic management of catheter-related infections (CRIs) often fails owing to the emergence of antimicrobial-resistant strains and/or biofilm/persister apparitions. Thus, we investigated the efficacy of two novel antimicrobial agents, i.e., the synthetic peptide SAAP-148 and the novel antibiotic halicin, against Gram-negative bacteria (GNB) colonizing catheters. The antibacterial, anti-biofilm, and anti-persister activities of both agents were evaluated against Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae strains. The enrolled strains were isolated from catheters and selected based on their resistance to at least three antibiotic classes and biofilm formation potential. Furthermore, the hemolysis and endotoxin neutralization abilities of these agents were explored. The bactericidal activity of both agents was reduced in urine and plasma as compared to buffered saline. In a dose-dependent manner, SAAP-148 and halicin reduced bacterial counts in 24 h preformed biofilms on silicone elastomer discs and eliminated persisters originating from antibiotic-exposed mature 7-day biofilms, with halicin being less effective than SAAP-148. Importantly, SAAP-148 and halicin acted synergistically on E. coli and K. pneumoniae biofilms but not on A. baumannii biofilms. The peptide, but not halicin, decreased the production of IL-12p40 upon exposure to UV-killed bacteria. This preliminary study showed that SAAP-148 and halicin alone/in combination are promising candidates to fight GNB colonizing catheters.