0-TESTO COMPLETO.pdf - Fondazione Santa Lucia

Sezione III: Attività per progetti
BACKGROUND AND SIGNIFICANCE
Bacterial infections are frequently associated with indwelling medical
devices.
In recent decades, the development of novel polymeric biomaterials
has allowed the manufacturing of a large number of medical devices
including orthopaedic prostheses, heart valves, intravascular catheters and
biliary stents, providing clinicians with useful means to improve healthcare.
However, infectious complications, including bloodstream infections,
septic thrombophlebitis, endocarditis, metastatic infections and sepsis, are
often associated with their use [Costerton et al. 1999; Donelli et al. 2001;
Parsek, Singh 2003]. It is well known that microorganisms adhere to
implanted medical devices by forming a sessile multicellular community
encased in a hydrated matrix of polysaccharides and proteins, the socalled
biofilm [Donlan, Costerton 2002]. As the biofilm thickness
increases, there is a progressive dispersal of single cells and/or bacterial
clusters of different sizes which can be considered the main promoters of
the infectious process [Fux et al. 2004]. Treatment of device-related infections
with conventional antimicrobials frequently fails because biofilmgrowing
microorganisms are much more resistant to antimicrobial agents
than planktonic cells [Stewart, Costerton 2001]. Hypothetical mechanisms
for biofilm resistance include the slow growth of persister cells within
biofilms [Shah et al. 2006] and the restricted penetration of antibiotics
within the biofilm due to the exopolysaccharide matrix produced by the
microorganisms themselves [Mah, O’Toole 2001]. Depending on the
involved body site and the mode of implant, different fungal and bacterial
species may contribute to the establishment of monospecies or multispecies
biofilms [Rickard et al. 2003]. The gram-positive species Staphylococcus
epidermidis, S. aureus and Enterococcus faecalis represent more
than 50% of the species isolated from device-associated infections. Candida
spp., Pseudomonas aeruginosa and a few other gram-negative species
represent the remaining causative agents.
The incidence of device-related infections is dramatically increasing, its
relevance being particularly due to the high rates of morbidity and mortality
directly associated with these infections. The Centers for Disease Control and
Prevention has estimated that approximately 80,000 central venous catheterassociated
bloodstream infections occur in intensive care units in the United
States each year [O’Grady et al. 2002]. The treatment of these infections
involves prolonged hospital stays and increased medical costs.
Since the early 1980’s, a number of strategies have been developed to prevent
device-related infections. Most of these are based on the use of antiadhesive,
antiseptic and antibiotic coatings of catheters [Donelli, Francolini 2001;
Kaplan 2005]. However, results obtained so far did not reach enough clinical
relevance to consider these medicated catheters as definitive substitutes for
conventional ones. For these reasons, further research efforts are still needed
to design novel medical devices refractory to microbial colonization and
biofilm formation.
796 2009